Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| TRIO021 | Other Identifier | Roche | |
| 2012-004879-38 | EudraCT Number |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This is a randomized, multicenter, open-label, two-arm study in treatment-naive participants with operable, locally advanced, or inflammatory, centrally-assessed HER2-positive early breast cancer (EBC) whose primary tumors were greater than or equal to (>/=) 2 centimeters (cm). The study was designed to evaluate the efficacy and safety of trastuzumab emtansine + pertuzumab (experimental arm; T-DM1 + P) versus chemotherapy, trastuzumab + pertuzumab (control arm; TCH + P). The study comprised a neoadjuvant treatment period, followed by surgery, and an adjuvant treatment period.
Treatment can be stopped due to disease recurrence, unacceptable toxicity, withdrawal of consent, or study termination.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Trastuzumab (TCH) + Pertuzumab | Active Comparator | Participants will receive pertuzumab 840 milligrams (mg) (loading dose) and 420 mg (maintenance dose) intravenous (IV) infusion followed by trastuzumab 8 milligrams per kilogram (mg/kg) (loading dose) and 6 mg/kg (maintenance dose) IV infusion followed by docetaxel 75 milligrams per square meter (mg/m^2) IV infusion and carboplatin at a dose to achieve an area under the curve (AUC) of 6 milligrams per milliliter* minute (mg/mL*min) IV infusion every 3 weeks (q3w) for 6 cycles in neoadjuvant period. Participants will receive pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab 8 mg/kg (loading dose) and 6 mg/kg (maintenance dose) IV infusion q3w for rest of the cycles (12 cycles) in adjuvant period (up to a total of 18 cycles). |
|
| Trastuzumab Emtansine (T-DM1) + Pertuzumab | Experimental | Participants will receive pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab emtansine 3.6 mg/kg IV infusion q3w for a total of 18 cycles (6 cycles of neoadjuvant period and 12 cycles of adjuvant period). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Carboplatin | Drug | Carboplatin IV infusion at a dose to achieve an AUC of 6 mg*min/mL q3w |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Total Pathological Complete Response (tpCR) Assessed Based on Tumor Samples | tpCR was assessed by local pathology review on samples taken at surgery following completion of neoadjuvant therapy. tpCR was defined as the absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes ( that is [i.e.], ypT0/is, ypN0 in the American Joint Committee on Cancer [AJCC] staging system, 7th edition). Percentage of participants with tpCR was reported. | Pre-surgery (within 6 weeks after neoadjuvant therapy; up to approximately 6 months) |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival | Overall survival in the overall study population was defined as the time from the date of randomization to the date of death from any cause. 3 years OS event-free rate per randomized treatment arms in the ITT population were estimated using the Kaplan-Meier method and estimated the probability of a patient being event-free after 3 years after treatment. | From randomization until death (up to approximately 47 months) |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| St. Jude Heritage Healthcare; Virgiia K.Crosson Can Ctr | Fullerton | California | 92835 | United States | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36631725 | Derived | de Haas SL, Slamon DJ, Martin M, Press MF, Lewis GD, Lambertini C, Prat A, Lopez-Valverde V, Boulet T, Hurvitz SA. Tumor biomarkers and efficacy in patients treated with trastuzumab emtansine + pertuzumab versus standard of care in HER2-positive early breast cancer: an open-label, phase III study (KRISTINE). Breast Cancer Res. 2023 Jan 11;25(1):2. doi: 10.1186/s13058-022-01587-z. | |
| 31157583 |
Not provided
Not provided
A total of 574 participants were screened at 65 sites in 10 countries, of which 444 participants were randomized in two arms: Trastuzumab (TCH) + Pertuzumab (P) (Arm A) and Trastuzumab Emtansine (TDM1) + P (Arm B)
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | TCH + P | Participants received pertuzumab 840 milligrams (mg) (loading dose) and 420 mg (maintenance dose) intravenous (IV) infusion, trastuzumab 8 milligrams per kilogram (mg/kg) (loading dose) and 6 mg/kg (maintenance dose) IV infusion, docetaxel 75 milligrams per square meter (mg/m^2) IV infusion and carboplatin at a dose to achieve an area under the curve (AUC) of 6 milligrams per milliliter* minute (mg/mL*min) IV infusion every 3 weeks (q3w) for 6 cycles in neoadjuvant period. Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab 8 mg/kg (loading dose) and 6 mg/kg (maintenance dose) IV infusion q3w for rest of the cycles (12 cycles) in adjuvant period (up to a total of 18 cycles). |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Docetaxel | Drug | Docetaxel 75 mg/m^2 IV infusion q3w |
|
| Pertuzumab | Drug | Pertuzumab 840 mg (loading dose); and 420 mg (maintenance dose) IV infusion q3w |
|
|
| Trastuzumab | Drug | Trastuzumab 8 mg/kg (loading dose); and 6 mg/kg (maintenance dose) IV infusion q3w |
|
|
| Trastuzumab Emtansine | Drug | Trastuzumab Emtansine 3.6 mg/kg IV infusion q3w |
|
|
| Percentage of Participants Who Received Breast-Conserving Surgery (BCS) | BCS rate was defined as the percentage of participants who achieve BCS out of the ITT population of participants without inflammatory breast cancer. | Surgery performed after completion of neoadjuvant therapy (approximately 6 months after neoadjuvant period) |
| Event-Free Survival | Event-free survival (EFS) is defined as the time from randomization to disease progression or disease recurrence (local, regional, distant, or contralateral, invasive or non-invasive), or death from any cause. 3 years EFS rate per randomized treatment arms in the ITT population were estimated using the Kaplan-Meier method and estimated the probability of a patient being event-free after 3 years after treatment. | From randomization up to disease progression or recurrence or death (up to approximately 47 months) |
| Invasive Disease-free Survival (IDFS) | IDFS is defined only for participants who undergo surgery. IDFS is defined as the time from surgery to the first documented occurrence of an IDFS event, defined as: Ipsilateral invasive breast tumor recurrence; Ipsilateral local-regional invasive breast cancer recurrence; Distant recurrence; Contralateral invasive breast cancer; and death from any cause. 3 years of IDFS event-free rate per randomized treatment arms in the ITT population were estimated using the Kaplan-Meier method and estimated the probability of a patient being event-free after 3 years after treatment. | From surgery to the first documented occurrence of IDFC event (up to approximately 47 months) |
| Percentage of Participants by Response for Neuropathy Single Item | Participants answered the question "Did you have tingling hands/feet?", from the Modified Quality of Life Questionnaire Breast Cancer 23 (mQLQ-BR23), on a 5-point scale (1 'Not at all', 2 'A little', 3 'Somewhat', 4 'Quite a bit', 5 'Very much'). Percentage of participants by each response was reported. | Baseline,Cycle(C) 3,C5 of neoadjuvant period (each C=21 days); pre-surgery visit (within 6weeks after neoadjuvant therapy; up to approx 6months), C4 & 8 of Adjuvant Period (each C=21 days), End of Treatment, Follow up 2 & 4 (approx 47 months) |
| Percentage of Participants by Response for Skin Problem Single Items | Participants answered the Question 1 "Did itching skin bother you?" and Question 2 "Have you had skin problems?", from the mQLQ-BR23, on a 5-point scale (1 'Not at all', 2 'A little', 3 'Somewhat', 4 'Quite a bit', 5 'Very much'). Percentage of participants by each response was reported. | Baseline,Cycle(C) 3,C5 of neoadjuvant period (each C=21 days); pre-surgery visit (within 6weeks after neoadjuvant therapy; up to approx 6months), C4 & 8 of Adjuvant Period (each C=21 days), End of Treatment, Follow up 2 & 4 (approx 47 months) |
| Percentage of Participants With a Clinically Meaningful Deterioration in Global Health Status (GHS)/Quality of Life (QoL) Score | Participants rated their quality of life (global health status) on European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ- C30), with total scores ranging from 0 (worst) to 100 (best); where higher score indicates better quality of life. Clinically meaningful deterioration in GHS/QoL was defined as a decrease in score of 10 points in GHS/QoL. | From Baseline (Day 1 Cycle 1) to Cycle 6 (each cycle = 21 days) in neoadjuvant period |
| Time to Clinically Meaningful Deterioration in GHS/QoL Score | Participants rated their quality of life (global health status) on EORTC QLQ C-30, with total scores ranging from 0 (worst) to 100 (best); where higher score indicates better quality of life. Time to deterioration was defined as the time from baseline to first 10-point (or greater) decrease as measured by GHS/QoL. All valid GHS/QoL questionnaires of the neoadjuvant phase including surgery were used. Participants without deterioration were censored at the time of completing the last GHS/QoL plus 1 day. Median time to deterioration was estimated with Kaplan-Meier method. The 95% confidence interval (CI) for the median was computed using the method of Brookmeyer and Crowley. | From Baseline (Day 1 Cycle 1) to Cycle 6 (each cycle = 21 days) in neoadjuvant period |
| Time to Clinically Meaningful Deterioration in Function Subscale | Participants rated their function on EORTC QLQ C-30, with total scores ranging from 0 (worst) to 100 (best); where higher score indicates better functioning. Time to deterioration was defined as the time from baseline to first 10-point (or greater) decrease as measured by physical function; to first 14-point (or greater) decrease as measured by role function, to first 7-point (or greater) decrease as measured by cognitive function. Median time to deterioration was estimated with Kaplan-Meier method. The 95% CI for the median was computed using the method of Brookmeyer and Crowley. | From Baseline (Day 1 Cycle 1) to Cycle 6 (each cycle = 21 days) in neoadjuvant period |
| Maximum Observed Serum Concentration (Cmax) of Trastuzumab | Only participants who received trastuzumab were to be analyzed for this outcome. | 15-30 minutes (min) post-study treatment infusion (infusion duration = 90 min) on Day 1 of Cycle 1 and 6 (each cycle = 21 days) in neoadjuvant and adjuvant period |
| Cmax of Trastuzumab Emtansine and Total Trastuzumab | Only participants who received trastuzumab emtansine were to be analyzed for this outcome. | 15-30 min post-study treatment infusion (infusion duration = 90 min) on Day 1 of Cycle 1 and 6 (each cycle = 21 days) in neoadjuvant and adjuvant period. |
| Minimum Observed Serum Concentration (Cmin) of Trastuzumab | Only participants who received trastuzumab were to be analyzed for this outcome. | Pre-study treatment infusion (0 hours [hr]) (infusion duration = 90 min) on Day 1 of Cycle 6 (cycle length = 21 days) in neoadjuvant and adjuvant period |
| Cmin of Trastuzumab Emtansine and Total Trastuzumab | Only participants who received trastuzumab emtansine were to be analyzed for this outcome. | Pre-study treatment infusion (0 hr) (infusion duration = 90 min) on Day 1 of Cycle 6 (cycle length = 21 days) in neoadjuvant and adjuvant period |
| Plasma N2'-Deacetyl-N2'-(3-mercapto-1-oxopropyl)-Maytansine (DM1) Concentrations | DM1 is the metabolite of trastuzumab emtansine. Only participants who received trastuzumab emtansine were to be analyzed for this outcome. | 15-30 min post-study treatment infusion (Cmax) on Day 1 of Cycle 1 and 6 in neoadjuvant and adjuvant period |
| Serum Levels of Plasma DM1-Containing Catabolites Concentrations (in ng/mL) (Nonreducible Thioether Linker [MCC]-DM1 and Lysine [Lys]-MCC-DM1) | 15-30 min post-study treatment infusion (Cmax) on Day 1 of Cycle 1 and 6 in neoadjuvant and adjuvant period |
| Percentage of Participants With ATA to Trastuzumab | Baseline (Pre-trastuzumab [0 hr] infusion [infusion duration = 90 min] on Day 1 of Cycle 1); post-baseline (Pre-trastuzumab infusion [0 hr] on Day 1 of Cycle 6) (each cycle = 21 days) in neoadjuvant and adjuvant period |
| Percentage of Participants by Response for Hair Loss Single Item | Participants answered the Question "Have you lost any hair?", from the mQLQ-BR23, on a 5-point scale (1 'Not at all', 2 'A little', 3 'Somewhat', 4 'Quite a bit', 5 'Very much'). Percentage of participants by each response was reported. | Baseline,Cycle(C) 3, C5 of neoadjuvant period (each C=21 days); pre-surgery visit (within 6weeks after neoadjuvant therapy; up to approx 6months), C4 & 8 of Adjuvant Period (each C=21 days), End of Treatment, Follow up 2 & 4(approx 47 months) |
| Percentage of Participants With Selected Adverse Events (AEs) | Selected AEs included hepatotoxicity, pulmonary toxicity, cardiac dysfunction, neutropenia, thrombocytopenia, peripheral neuropathy, hemorrhage, infusion related reaction (IRR)/hypersensitivity, IRR/Hypersensitivity symptoms, rash, diarrhea and mucositis. An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. | Baseline to end of study (approximately 47 months) |
| Percentage of Participants With a Clinically Meaningful Deterioration in Function Subscales | Participants rated their function on EORTC QLQ C-30, with total score and single-item (physical, cognitive and role functioning) scores ranging from 0 (worst) to 100 (best); where higher score indicates better functioning. Clinically meaningful deterioration was defined as a decrease in score of 10 points in physical function; decrease of 7 points in cognitive function and decrease of 14 points in role function. | From Baseline (Day 1 Cycle 1) to Cycle 6 (each cycle = 21 days) in neoadjuvant period |
| Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to TDM-1 | Participants were considered post-baseline ATA positive if they had ATAs post-baseline that were either treatment-induced or treatment-enhanced. Participants had treatment-induced ATAs if they had a negative or missing ATA result at baseline, and at least one positive ATA result post-baseline. Participants had treatment-enhanced ATAs if they had a positive ATA result at baseline, and at least one positive ATA result post-baseline that was greater than or equal to (>/=) 0.60 titer units higher than the result at baseline. | Baseline (b) (Pre-TDM1 [0 hr] infusion [infusion duration = 90 min] on Day 1 of Cycle 1); post-baseline (pb) (Pre-TDM1 infusion [0 hr] on Day 1 of Cycle 6) (each cycle = 21 days) in neoadjuvant and adjuvant period |
| Percentage of Participants With a Clinically Meaningful Increase in Symptom Subscales | Participants rated their symptoms on EORTC QLQ C-30 and mQLQ-BR23, with total scores ranging from 0 (worst) to 100 (best); where higher score indicates greater degree of symptoms. Clinically meaningful increase in symptoms was defined as an increase in score (deterioration) of 11 points in nausea and vomiting, pain, dyspnea; increase of 9 points in insomnia; increase of 14 points in appetite loss; increase of 15 points in diarrhea, constipation; increase of 10 points in fatigue, systemic therapy side effects, hair loss. | From Baseline (Day 1 Cycle 1) to Cycle 6 (each cycle = 21 days) in neoadjuvant period |
| Cancer Care Assoc Med Group |
| Los Angeles |
| California |
| 90095-1772 |
| United States |
| Coastal Integrative Cancer Care | San Luis Obispo | California | 93401 | United States |
| Central Coast Medical Oncology | Santa Maria | California | 93454 | United States |
| UCLA Hematology/Oncology | Santa Monica | California | 90404 | United States |
| Memorial Cancer Institute | Hollywood | Florida | 33021 | United States |
| Md Anderson Cancer Center Orlando | Orlando | Florida | 32806 | United States |
| New England Cancer Specialists | Scarborough | Maine | 04074 | United States |
| Comprehensive Cancer Centers of Nevada - Henderson | Henderson | Nevada | 89052 | United States |
| ProHEALTH Care Associates LLP | Lake Success | New York | 11042 | United States |
| Montefiore Medical Center | The Bronx | New York | 10467 | United States |
| Hope A Women's Cancer Center | Asheville | North Carolina | 28806 | United States |
| Levine Cancer Institute | Charlotte | North Carolina | 28204 | United States |
| Roper Bon Secours St. Francis Cancer Center | Charleston | South Carolina | 29414 | United States |
| Sarah Cannon Research Institute | Nashville | Tennessee | 37203 | United States |
| MD Anderson Cancer Center | Houston | Texas | 77030 | United States |
| UZ Antwerpen | Edegem | 2650 | Belgium |
| UZ Leuven Gasthuisberg | Leuven | 3000 | Belgium |
| Clinique Saint-Joseph | Liège | 4000 | Belgium |
| Clinique Ste-Elisabeth, Pharmacie | Namur | 5000 | Belgium |
| Sint Augustinus Wilrijk | Wilrijk | 2610 | Belgium |
| Cross Cancer Institute ; Dept of Medical Oncology | Edmonton | Alberta | T6G 1Z2 | Canada |
| Sunnybrook Health Sciences Centre | Toronto | Ontario | M4N 3M5 | Canada |
| St. Michael'S Hospital | Toronto | Ontario | M5B 1W8 | Canada |
| Chum Hospital Notre Dame | Montreal | Quebec | H2L 4M1 | Canada |
| McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology | Montreal | Quebec | H3T 1E2 | Canada |
| CHU de Québec - Hôpital du Saint-Sacrement / ONCOLOGY | Québec | G1S 4L8 | Canada |
| Ico - Paul Papin | Angers | 49000 | France |
| HOPITAL JEAN MINJOZ; Oncologie | Besançon | 25030 | France |
| Hopital Morvan | Brest | 29200 | France |
| CHD Les Oudairies | La Roche-sur-Yon | 85925 | France |
| Centre Oscar Lambret | Lille | 59020 | France |
| Institut Paoli Calmettes | Marseille | 13009 | France |
| Centre Catherine De Sienne | Nantes | 44202 | France |
| Centre Rene Gauducheau | Saint-Herblain | 44805 | France |
| Nouvel Hopital Civil - CHU Strasbourg | Strasbourg | 67091 | France |
| Klinikum Sindelfingen-Böblingen; Frauenklinik | Böblingen | 71032 | Germany |
| Luisenkrankenhaus GmbH, Brustzentrum | Düsseldorf | 40235 | Germany |
| Universitätsklinikum Erlangen; Frauenklinik | Erlangen | 91054 | Germany |
| Universitätsklinikum Mainz | Mainz | 55131 | Germany |
| Interdisziplinäres Onkologisches Zentrum | München | 80336 | Germany |
| Moscow City Oncology Hospital #62 | Moscovskaya Oblast | Moscow Oblast | 143423 | Russia |
| Regional Oncology Hospital Of Kursk; Chemotherapy | Kislino, Kursk Region | 305524 | Russia |
| S.I. Russian Oncological Research Center n.a. N.N. Blokhin | Moscow | 115478 | Russia |
| State Inst. Of Healthcare Orenburg Regional Clinical Oncology Dis | Orenburg | 460021 | Russia |
| Saint-Petersburg City Clinical Oncology Dispensary | Saint Petersburg | 197022 | Russia |
| Railway Clinical Hospital on Saratov - 2 Station Oao "Rzhd" | Saratov | 410004 | Russia |
| National Cancer Center | Gyeonggi-do | 10408 | South Korea |
| Seoul National University Bundang Hospital | Gyeonggi-do | 13620 | South Korea |
| Seoul National University Hospital | Seoul | 03080 | South Korea |
| Severance Hospital | Seoul | 03722 | South Korea |
| Asan Medical Center - Oncology | Seoul | 05505 | South Korea |
| Samsung Medical Center | Seoul | 6351 | South Korea |
| Corporacio Sanitaria Parc Tauli; Servicio de Oncologia | Sabadell | Barcelona | 08208 | Spain |
| IInstituto Oncologico de San Sebastian, Oncologikoa; Servicio de Oncologia | Donostia / San Sebastian | Guipuzcoa | 20014 | Spain |
| Hospital Universitari de Lleida Arnau de Vilanova | Lleida | Lerida | 25198 | Spain |
| Complejo Hospitalario Universitario A Coruña (CHUAC, Materno Infantil), Oncología | A Coruña | 15006 | Spain |
| Hospital Nuestra Señora de Sonsoles; servicio de Oncologia | Ávila | 05071 | Spain |
| Hospital del Mar; Servicio de Oncologia | Barcelona | 08003 | Spain |
| Fundacio Santa Creu I Sant Pau | Barcelona | 08006 | Spain |
| Complejo Hospitalario de Jaen | Jaén | 23007 | Spain |
| Hospital General Universitario Gregorio Marañon; Servicio de Oncologia | Madrid | 28007 | Spain |
| Hospital Universitario Clínico San Carlos; Servicio de Oncologia | Madrid | 28040 | Spain |
| Centro Integral Oncologico Clara Campal (CIOCC); Dirección Médica | Madrid | 28050 | Spain |
| Hospital Quiron de Madrid; Servicio de Oncologia | Madrid | 28223 | Spain |
| Hospital Universitario Virgen de la Victoria | Málaga | 29010 | Spain |
| Hospital Universitario Virgen del Rocio | Seville | 41013 | Spain |
| Hospital Clinico Universitario de Valencia | Valencia | 46010 | Spain |
| Hospital Universitario Miguel Servet; Servicio Oncologia | Zaragoza | 50009 | Spain |
| Kaohsiung Medical Uni Chung-Ho Hospital; Dept of Surgery | Kaohsiung City | 807 | Taiwan |
| National Taiwan Uni Hospital | Taipei | 10041 | Taiwan |
| Mackay Memorial Hospital; Dept of Surgery | Taipei | 104 | Taiwan |
| Koo Foundation Sun Yat-Sen Cancer Center; Hemato-Oncology | Taipei | 112 | Taiwan |
| Taipei Veterans General Hospital | Taipei | 112 | Taiwan |
| Tri-Service General Hospital | Taipei | 11490 | Taiwan |
| Cherkassy Regional Oncological Hospital | Cherkassy | 18009 | Ukraine |
| State Medical Academy; Oncology | Dnipropetrovsk | 43102 | Ukraine |
| Karkiv Regional Oncology Center | Kharkiv | 61070 | Ukraine |
| Lvov State Regional Center | Lviv | 79031 | Ukraine |
| Derived |
| Hurvitz SA, Martin M, Jung KH, Huang CS, Harbeck N, Valero V, Stroyakovskiy D, Wildiers H, Campone M, Boileau JF, Fasching PA, Afenjar K, Spera G, Lopez-Valverde V, Song C, Trask P, Boulet T, Sparano JA, Symmans WF, Thompson AM, Slamon D. Neoadjuvant Trastuzumab Emtansine and Pertuzumab in Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: Three-Year Outcomes From the Phase III KRISTINE Study. J Clin Oncol. 2019 Sep 1;37(25):2206-2216. doi: 10.1200/JCO.19.00882. Epub 2019 Jun 3. |
| 29175149 | Derived | Hurvitz SA, Martin M, Symmans WF, Jung KH, Huang CS, Thompson AM, Harbeck N, Valero V, Stroyakovskiy D, Wildiers H, Campone M, Boileau JF, Beckmann MW, Afenjar K, Fresco R, Helms HJ, Xu J, Lin YG, Sparano J, Slamon D. Neoadjuvant trastuzumab, pertuzumab, and chemotherapy versus trastuzumab emtansine plus pertuzumab in patients with HER2-positive breast cancer (KRISTINE): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2018 Jan;19(1):115-126. doi: 10.1016/S1470-2045(17)30716-7. Epub 2017 Nov 23. |
| FG001 | T-DM1 + P | Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab emtansine 3.6 mg/kg IV infusion q3w for a total of 18 cycles (6 cycles of neoadjuvant period and 12 cycles of adjuvant period). |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | TCH + P | Participants received pertuzumab 840 milligrams (mg) (loading dose) and 420 mg (maintenance dose) intravenous (IV) infusion, trastuzumab 8 milligrams per kilogram (mg/kg) (loading dose) and 6 mg/kg (maintenance dose) IV infusion, docetaxel 75 milligrams per square meter (mg/m^2) IV infusion and carboplatin at a dose to achieve an area under the curve (AUC) of 6 milligrams per milliliter* minute (mg/mL*min) IV infusion every 3 weeks (q3w) for 6 cycles in neoadjuvant period. Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab 8 mg/kg (loading dose) and 6 mg/kg (maintenance dose) IV infusion q3w for rest of the cycles (12 cycles) in adjuvant period (up to a total of 18 cycles). |
| BG001 | T-DM1 + P | Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab emtansine 3.6 mg/kg IV infusion q3w for a total of 18 cycles (6 cycles of neoadjuvant period and 12 cycles of adjuvant period). |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage of Participants With Total Pathological Complete Response (tpCR) Assessed Based on Tumor Samples | tpCR was assessed by local pathology review on samples taken at surgery following completion of neoadjuvant therapy. tpCR was defined as the absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes ( that is [i.e.], ypT0/is, ypN0 in the American Joint Committee on Cancer [AJCC] staging system, 7th edition). Percentage of participants with tpCR was reported. | The Intent-to-treat (ITT) Population comprised all randomized patients, whether or not they received any study treatment or completed a full course of study treatment. Patients were analyzed according to their randomized treatment. | Posted | Number | 95% Confidence Interval | Percentage of Participants | Pre-surgery (within 6 weeks after neoadjuvant therapy; up to approximately 6 months) |
|
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Overall Survival | Overall survival in the overall study population was defined as the time from the date of randomization to the date of death from any cause. 3 years OS event-free rate per randomized treatment arms in the ITT population were estimated using the Kaplan-Meier method and estimated the probability of a patient being event-free after 3 years after treatment. | The ITT Population comprised all randomized patients, whether or not they received any study treatment or completed a full course of study treatment. Patients were analyzed according to their randomized treatment. | Posted | Number | 95% Confidence Interval | Probability | From randomization until death (up to approximately 47 months) |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants Who Received Breast-Conserving Surgery (BCS) | BCS rate was defined as the percentage of participants who achieve BCS out of the ITT population of participants without inflammatory breast cancer. | Posted | Number | 95% Confidence Interval | Percentage of Participants | Surgery performed after completion of neoadjuvant therapy (approximately 6 months after neoadjuvant period) |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Event-Free Survival | Event-free survival (EFS) is defined as the time from randomization to disease progression or disease recurrence (local, regional, distant, or contralateral, invasive or non-invasive), or death from any cause. 3 years EFS rate per randomized treatment arms in the ITT population were estimated using the Kaplan-Meier method and estimated the probability of a patient being event-free after 3 years after treatment. | The ITT Population comprised all randomized patients, whether or not they received any study treatment or completed a full course of study treatment. Patients were analyzed according to their randomized treatment. | Posted | Number | 95% Confidence Interval | Probability | From randomization up to disease progression or recurrence or death (up to approximately 47 months) |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Invasive Disease-free Survival (IDFS) | IDFS is defined only for participants who undergo surgery. IDFS is defined as the time from surgery to the first documented occurrence of an IDFS event, defined as: Ipsilateral invasive breast tumor recurrence; Ipsilateral local-regional invasive breast cancer recurrence; Distant recurrence; Contralateral invasive breast cancer; and death from any cause. 3 years of IDFS event-free rate per randomized treatment arms in the ITT population were estimated using the Kaplan-Meier method and estimated the probability of a patient being event-free after 3 years after treatment. | The ITT Population comprised all randomized patients, whether or not they received any study treatment or completed a full course of study treatment. Patients were analyzed according to their randomized treatment. | Posted | Number | 95% Confidence Interval | Probability | From surgery to the first documented occurrence of IDFC event (up to approximately 47 months) |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants by Response for Neuropathy Single Item | Participants answered the question "Did you have tingling hands/feet?", from the Modified Quality of Life Questionnaire Breast Cancer 23 (mQLQ-BR23), on a 5-point scale (1 'Not at all', 2 'A little', 3 'Somewhat', 4 'Quite a bit', 5 'Very much'). Percentage of participants by each response was reported. | ITT population of patients with both a baseline assessment and at least one post-treatment assessment in the respective single question are included in the analysis. | Posted | Number | Percentage of Participants | Baseline,Cycle(C) 3,C5 of neoadjuvant period (each C=21 days); pre-surgery visit (within 6weeks after neoadjuvant therapy; up to approx 6months), C4 & 8 of Adjuvant Period (each C=21 days), End of Treatment, Follow up 2 & 4 (approx 47 months) |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants by Response for Skin Problem Single Items | Participants answered the Question 1 "Did itching skin bother you?" and Question 2 "Have you had skin problems?", from the mQLQ-BR23, on a 5-point scale (1 'Not at all', 2 'A little', 3 'Somewhat', 4 'Quite a bit', 5 'Very much'). Percentage of participants by each response was reported. | ITT population of patients with both a baseline assessment and at least one post-treatment assessment in the respective single question are included in the analysis. | Posted | Number | Percentage of Participants | Baseline,Cycle(C) 3,C5 of neoadjuvant period (each C=21 days); pre-surgery visit (within 6weeks after neoadjuvant therapy; up to approx 6months), C4 & 8 of Adjuvant Period (each C=21 days), End of Treatment, Follow up 2 & 4 (approx 47 months) |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With a Clinically Meaningful Deterioration in Global Health Status (GHS)/Quality of Life (QoL) Score | Participants rated their quality of life (global health status) on European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ- C30), with total scores ranging from 0 (worst) to 100 (best); where higher score indicates better quality of life. Clinically meaningful deterioration in GHS/QoL was defined as a decrease in score of 10 points in GHS/QoL. | The Intent-to-treat (ITT) Population comprised all randomized participants, whether or not they received any study treatment or completed a full course of study treatment. Participants were analyzed according to their randomized treatment. As per protocol, the analysis for this outcome measure was focused on the neoadjuvant period only. | Posted | Number | Percentage of Participants | From Baseline (Day 1 Cycle 1) to Cycle 6 (each cycle = 21 days) in neoadjuvant period |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Time to Clinically Meaningful Deterioration in GHS/QoL Score | Participants rated their quality of life (global health status) on EORTC QLQ C-30, with total scores ranging from 0 (worst) to 100 (best); where higher score indicates better quality of life. Time to deterioration was defined as the time from baseline to first 10-point (or greater) decrease as measured by GHS/QoL. All valid GHS/QoL questionnaires of the neoadjuvant phase including surgery were used. Participants without deterioration were censored at the time of completing the last GHS/QoL plus 1 day. Median time to deterioration was estimated with Kaplan-Meier method. The 95% confidence interval (CI) for the median was computed using the method of Brookmeyer and Crowley. | The Intent-to-treat (ITT) Population comprised all randomized participants, whether or not they received any study treatment or completed a full course of study treatment. Participants were analyzed according to their randomized treatment. As per protocol, the analysis for this outcome measure was focused on the neoadjuvant period only. | Posted | Median | 95% Confidence Interval | months | From Baseline (Day 1 Cycle 1) to Cycle 6 (each cycle = 21 days) in neoadjuvant period |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Time to Clinically Meaningful Deterioration in Function Subscale | Participants rated their function on EORTC QLQ C-30, with total scores ranging from 0 (worst) to 100 (best); where higher score indicates better functioning. Time to deterioration was defined as the time from baseline to first 10-point (or greater) decrease as measured by physical function; to first 14-point (or greater) decrease as measured by role function, to first 7-point (or greater) decrease as measured by cognitive function. Median time to deterioration was estimated with Kaplan-Meier method. The 95% CI for the median was computed using the method of Brookmeyer and Crowley. | Patients of the ITT population with a baseline assessment and at least one post-treatment assessment was included in this analysis. | Posted | Median | 95% Confidence Interval | months | From Baseline (Day 1 Cycle 1) to Cycle 6 (each cycle = 21 days) in neoadjuvant period |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Maximum Observed Serum Concentration (Cmax) of Trastuzumab | Only participants who received trastuzumab were to be analyzed for this outcome. | The pharmacokinetic population comprised all patients who received at least one treatment dose of trastuzumab emtansine (for patients in the T-DM1 + P arm) or trastuzumab (for patients in the TCH + P arm), and had at least one post-treatment serum or plasma sample. | Posted | Mean | Standard Deviation | micrograms per milliliter (mcg/mL) | 15-30 minutes (min) post-study treatment infusion (infusion duration = 90 min) on Day 1 of Cycle 1 and 6 (each cycle = 21 days) in neoadjuvant and adjuvant period |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Cmax of Trastuzumab Emtansine and Total Trastuzumab | Only participants who received trastuzumab emtansine were to be analyzed for this outcome. | The pharmacokinetic population comprised all patients who received at least one treatment dose of trastuzumab emtansine (for patients in the T-DM1 + P arm) or trastuzumab (for patients in the TCH + P arm), and had at least one post-treatment serum or plasma sample. | Posted | Mean | Standard Deviation | mcg/mL | 15-30 min post-study treatment infusion (infusion duration = 90 min) on Day 1 of Cycle 1 and 6 (each cycle = 21 days) in neoadjuvant and adjuvant period. |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Minimum Observed Serum Concentration (Cmin) of Trastuzumab | Only participants who received trastuzumab were to be analyzed for this outcome. | The pharmacokinetic population comprised all patients who received at least one treatment dose of trastuzumab emtansine (for patients in the T-DM1 + P arm) or trastuzumab (for patients in the TCH + P arm), and had at least one post-treatment serum or plasma sample. | Posted | Mean | Standard Deviation | mcg/mL | Pre-study treatment infusion (0 hours [hr]) (infusion duration = 90 min) on Day 1 of Cycle 6 (cycle length = 21 days) in neoadjuvant and adjuvant period |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Cmin of Trastuzumab Emtansine and Total Trastuzumab | Only participants who received trastuzumab emtansine were to be analyzed for this outcome. | The pharmacokinetic population comprised all patients who received at least one treatment dose of trastuzumab emtansine (for patients in the T-DM1 + P arm) or trastuzumab (for patients in the TCH + P arm), and had at least one post-treatment serum or plasma sample. | Posted | Mean | Standard Deviation | mcg/mL | Pre-study treatment infusion (0 hr) (infusion duration = 90 min) on Day 1 of Cycle 6 (cycle length = 21 days) in neoadjuvant and adjuvant period |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Plasma N2'-Deacetyl-N2'-(3-mercapto-1-oxopropyl)-Maytansine (DM1) Concentrations | DM1 is the metabolite of trastuzumab emtansine. Only participants who received trastuzumab emtansine were to be analyzed for this outcome. | The pharmacokinetic population comprised all patients who received at least one treatment dose of trastuzumab emtansine (for patients in the T-DM1 + P arm) or trastuzumab (for patients in the TCH + P arm), and had at least one post-treatment serum or plasma sample. | Posted | Mean | Standard Deviation | nanograms per milliliter (ng/mL) | 15-30 min post-study treatment infusion (Cmax) on Day 1 of Cycle 1 and 6 in neoadjuvant and adjuvant period |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Serum Levels of Plasma DM1-Containing Catabolites Concentrations (in ng/mL) (Nonreducible Thioether Linker [MCC]-DM1 and Lysine [Lys]-MCC-DM1) | The pharmacokinetic population comprised all patients who received at least one treatment dose of trastuzumab emtansine (for patients in the T-DM1 + P arm) or trastuzumab (for patients in the TCH + P arm), and had at least one post-treatment serum or plasma sample. | Posted | Mean | Standard Deviation | ng/mL | 15-30 min post-study treatment infusion (Cmax) on Day 1 of Cycle 1 and 6 in neoadjuvant and adjuvant period |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With ATA to Trastuzumab | The participants included in this analysis were the participants who received at least one dose of trastuzumab and had at least one reported serum or plasma results. | Posted | Number | Percentage of participants | Baseline (Pre-trastuzumab [0 hr] infusion [infusion duration = 90 min] on Day 1 of Cycle 1); post-baseline (Pre-trastuzumab infusion [0 hr] on Day 1 of Cycle 6) (each cycle = 21 days) in neoadjuvant and adjuvant period |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants by Response for Hair Loss Single Item | Participants answered the Question "Have you lost any hair?", from the mQLQ-BR23, on a 5-point scale (1 'Not at all', 2 'A little', 3 'Somewhat', 4 'Quite a bit', 5 'Very much'). Percentage of participants by each response was reported. | ITT population of patients with both a baseline assessment and at least one post-treatment assessment in the respective single question are included in the analysis. | Posted | Number | Percentage of Participants | Baseline,Cycle(C) 3, C5 of neoadjuvant period (each C=21 days); pre-surgery visit (within 6weeks after neoadjuvant therapy; up to approx 6months), C4 & 8 of Adjuvant Period (each C=21 days), End of Treatment, Follow up 2 & 4(approx 47 months) |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With Selected Adverse Events (AEs) | Selected AEs included hepatotoxicity, pulmonary toxicity, cardiac dysfunction, neutropenia, thrombocytopenia, peripheral neuropathy, hemorrhage, infusion related reaction (IRR)/hypersensitivity, IRR/Hypersensitivity symptoms, rash, diarrhea and mucositis. An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. | The Safety Population comprised all patients who received at least one full or partial dose of any study treatment. Patients were analyzed according to the treatment they actually received. | Posted | Number | Percentage of Participants | Baseline to end of study (approximately 47 months) |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With a Clinically Meaningful Deterioration in Function Subscales | Participants rated their function on EORTC QLQ C-30, with total score and single-item (physical, cognitive and role functioning) scores ranging from 0 (worst) to 100 (best); where higher score indicates better functioning. Clinically meaningful deterioration was defined as a decrease in score of 10 points in physical function; decrease of 7 points in cognitive function and decrease of 14 points in role function. | The Intent-to-treat (ITT) Population comprised all randomized participants, whether or not they received any study treatment or completed a full course of study treatment. Participants were analyzed according to their randomized treatment. As per protocol, the analysis for this outcome measure was focused on the neoadjuvant period only. | Posted | Number | Percentage of Participants | From Baseline (Day 1 Cycle 1) to Cycle 6 (each cycle = 21 days) in neoadjuvant period |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to TDM-1 | Participants were considered post-baseline ATA positive if they had ATAs post-baseline that were either treatment-induced or treatment-enhanced. Participants had treatment-induced ATAs if they had a negative or missing ATA result at baseline, and at least one positive ATA result post-baseline. Participants had treatment-enhanced ATAs if they had a positive ATA result at baseline, and at least one positive ATA result post-baseline that was greater than or equal to (>/=) 0.60 titer units higher than the result at baseline. | The participants included in this analysis were the participants who received at least one dose of trastuzumab emtansine and had at least one reported serum or plasma results. | Posted | Number | Percentage of Participants | Baseline (b) (Pre-TDM1 [0 hr] infusion [infusion duration = 90 min] on Day 1 of Cycle 1); post-baseline (pb) (Pre-TDM1 infusion [0 hr] on Day 1 of Cycle 6) (each cycle = 21 days) in neoadjuvant and adjuvant period |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With a Clinically Meaningful Increase in Symptom Subscales | Participants rated their symptoms on EORTC QLQ C-30 and mQLQ-BR23, with total scores ranging from 0 (worst) to 100 (best); where higher score indicates greater degree of symptoms. Clinically meaningful increase in symptoms was defined as an increase in score (deterioration) of 11 points in nausea and vomiting, pain, dyspnea; increase of 9 points in insomnia; increase of 14 points in appetite loss; increase of 15 points in diarrhea, constipation; increase of 10 points in fatigue, systemic therapy side effects, hair loss. | The Intent-to-treat (ITT) Population comprised all randomized participants, whether or not they received any study treatment or completed a full course of study treatment. Participants were analyzed according to their randomized treatment. As per protocol, the analysis for this outcome measure was focused on the neoadjuvant period only. | Posted | Number | Percentage of Participants | From Baseline (Day 1 Cycle 1) to Cycle 6 (each cycle = 21 days) in neoadjuvant period |
|
From Baseline up to approximately 47 months
Safety population was analyzed.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | TCH + P | Participants received pertuzumab 840 milligrams (mg) (loading dose) and 420 mg (maintenance dose) intravenous (IV) infusion, trastuzumab 8 milligrams per kilogram (mg/kg) (loading dose) and 6 mg/kg (maintenance dose) IV infusion, docetaxel 75 milligrams per square meter (mg/m^2) IV infusion and carboplatin at a dose to achieve an area under the curve (AUC) of 6 milligrams per milliliter* minute (mg/mL*min) IV infusion every 3 weeks (q3w) for 6 cycles in neoadjuvant period. Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab 8 mg/kg (loading dose) and 6 mg/kg (maintenance dose) IV infusion q3w for rest of the cycles (12 cycles) in adjuvant period (up to a total of 18 cycles). | 5 | 219 | 70 | 219 | 217 | 219 |
| EG001 | T-DM1 + P | Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab emtansine 3.6 mg/kg IV infusion q3w for a total of 18 cycles (6 cycles of neoadjuvant period and 12 cycles of adjuvant period). | 6 | 223 | 30 | 223 | 212 | 223 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Cardiac failure | Cardiac disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Sinus tachycardia | Cardiac disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Gastritis | Gastrointestinal disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Haemorrhoids | Gastrointestinal disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Ileus | Gastrointestinal disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Anaphylactic reaction | Immune system disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Hypersensitivity | Immune system disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Bacteraemia | Infections and infestations | MedDRA 18.1 | Non-systematic Assessment |
| |
| Breast cellulitis | Infections and infestations | MedDRA 18.1 | Non-systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA 18.1 | Non-systematic Assessment |
| |
| Clostridium difficile colitis | Infections and infestations | MedDRA 18.1 | Non-systematic Assessment |
| |
| Clostridium difficile infection | Infections and infestations | MedDRA 18.1 | Non-systematic Assessment |
| |
| Device related infection | Infections and infestations | MedDRA 18.1 | Non-systematic Assessment |
| |
| Diarrhoea infectious | Infections and infestations | MedDRA 18.1 | Non-systematic Assessment |
| |
| Enterocolitis infectious | Infections and infestations | MedDRA 18.1 | Non-systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA 18.1 | Non-systematic Assessment |
| |
| Gastroenteritis norovirus | Infections and infestations | MedDRA 18.1 | Non-systematic Assessment |
| |
| Kidney infection | Infections and infestations | MedDRA 18.1 | Non-systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 18.1 | Non-systematic Assessment |
| |
| Postoperative wound infection | Infections and infestations | MedDRA 18.1 | Non-systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA 18.1 | Non-systematic Assessment |
| |
| Skin infection | Infections and infestations | MedDRA 18.1 | Non-systematic Assessment |
| |
| Subcutaneous abscess | Infections and infestations | MedDRA 18.1 | Non-systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 18.1 | Non-systematic Assessment |
| |
| Wound infection | Infections and infestations | MedDRA 18.1 | Non-systematic Assessment |
| |
| Subcutaneous haematoma | Injury, poisoning and procedural complications | MedDRA 18.1 | Non-systematic Assessment |
| |
| Lipase increased | Investigations | MedDRA 18.1 | Non-systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA 18.1 | Non-systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Hypermagnesaemia | Metabolism and nutrition disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Intraductal proliferative breast lesion | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.1 | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Neuropathy peripheral | Nervous system disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Transient ischaemic attack | Nervous system disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Renal failure | Renal and urinary disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Adenomyosis | Reproductive system and breast disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Breast haematoma | Reproductive system and breast disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Hypertensive crisis | Vascular disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Shock haemorrhagic | Vascular disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Procedural intestinal perforation | Injury, poisoning and procedural complications | MedDRA 18.1 | Non-systematic Assessment |
| |
| Left ventricular dysfunction | Cardiac disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Device related thrombosis | General disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Nodular regenerative hyperplasia | Hepatobiliary disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Breast abscess | Infections and infestations | MedDRA 18.1 | Non-systematic Assessment |
| |
| Seroma | Injury, poisoning and procedural complications | MedDRA 18.1 | Non-systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Cervix carinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.1 | Non-systematic Assessment |
| |
| Neuroendocrine tumour | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.1 | Non-systematic Assessment |
| |
| Uterine leiomyoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.1 | Non-systematic Assessment |
| |
| Bronchiectasis | Respiratory, thoracic and mediastinal disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 18.1 | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Dry eye | Eye disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Lacrimation increased | Eye disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Haemorrhoids | Gastrointestinal disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Chills | General disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Mucosal inflammation | General disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 18.1 | Non-systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 18.1 | Non-systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 18.1 | Non-systematic Assessment |
| |
| Radiation skin injury | Injury, poisoning and procedural complications | MedDRA 18.1 | Non-systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 18.1 | Non-systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 18.1 | Non-systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA 18.1 | Non-systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA 18.1 | Non-systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA 18.1 | Non-systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA 18.1 | Non-systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Hypoaesthesia | Nervous system disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Neuropathy peripheral | Nervous system disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Breast pain | Reproductive system and breast disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Nail discolouration | Skin and subcutaneous tissue disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Nail disorder | Skin and subcutaneous tissue disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Hot flush | Vascular disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Gingival bleeding | Gastrointestinal disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Hypersensitivity | Immune system disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA 18.1 | Non-systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 18.1 | Non-systematic Assessment |
|
The reported results are interim only.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Communications | Hoffmann-La Roche | 800 821-8590 | genentech@druginfo.com |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D016190 | Carboplatin |
| D000077143 | Docetaxel |
| C485206 | pertuzumab |
| D000068878 | Trastuzumab |
| D000080044 | Ado-Trastuzumab Emtansine |
| ID | Term |
|---|---|
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D008453 | Maytansine |
| D018942 | Macrolides |
| D007783 | Lactones |
| D047029 | Lactams, Macrocyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
Not provided
Not provided
| Male |
|
Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab emtansine 3.6 mg/kg IV infusion q3w for a total of 18 cycles (6 cycles of neoadjuvant period and 12 cycles of adjuvant period). |
|
|
|
|
|
|
| T-DM1 + P |
Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab emtansine 3.6 mg/kg IV infusion q3w for a total of 18 cycles (6 cycles of neoadjuvant period and 12 cycles of adjuvant period). |
|
|
|
| OG001 | T-DM1 + P | Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab emtansine 3.6 mg/kg IV infusion q3w for a total of 18 cycles (6 cycles of neoadjuvant period and 12 cycles of adjuvant period). |
|
|
|
| OG001 |
| T-DM1 + P |
Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab emtansine 3.6 mg/kg IV infusion q3w for a total of 18 cycles (6 cycles of neoadjuvant period and 12 cycles of adjuvant period). |
|
|
| T-DM1 + P |
Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab emtansine 3.6 mg/kg IV infusion q3w for a total of 18 cycles (6 cycles of neoadjuvant period and 12 cycles of adjuvant period). |
|
|
| OG001 | T-DM1 + P | Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab emtansine 3.6 mg/kg IV infusion q3w for a total of 18 cycles (6 cycles of neoadjuvant period and 12 cycles of adjuvant period). |
|
|
|
| OG001 | T-DM1 + P | Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab emtansine 3.6 mg/kg IV infusion q3w for a total of 18 cycles (6 cycles of neoadjuvant period and 12 cycles of adjuvant period). |
|
|
|
| OG001 | T-DM1 + P | Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab emtansine 3.6 mg/kg IV infusion q3w for a total of 18 cycles (6 cycles of neoadjuvant period and 12 cycles of adjuvant period). |
|
|
| Participants |
|
|
|
| Participants |
|
|
|
|
|
|
Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab emtansine 3.6 mg/kg IV infusion q3w for a total of 18 cycles (6 cycles of neoadjuvant period and 12 cycles of adjuvant period). |
|
|
| T-DM1 + P |
Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab emtansine 3.6 mg/kg IV infusion q3w for a total of 18 cycles (6 cycles of neoadjuvant period and 12 cycles of adjuvant period). |
|
|
| OG001 | T-DM1 + P | Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab emtansine 3.6 mg/kg IV infusion q3w for a total of 18 cycles (6 cycles of neoadjuvant period and 12 cycles of adjuvant period). |
|
|
|
|
|
| OG001 | T-DM1 + P | Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab emtansine 3.6 mg/kg IV infusion q3w for a total of 18 cycles (6 cycles of neoadjuvant period and 12 cycles of adjuvant period). |
|
|