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| ID | Type | Description | Link |
|---|---|---|---|
| 2016-002200-39 | EudraCT Number |
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This is a multi-center, randomized phase II trial that will randomise women with ER-positive, HER2-negative (Human Epidermal Growth factor Receptor 2-negative) metastatic or locally relapsed breast cancer in a ratio of 1:1 to receive a metronomic regimen of vinorelbine plus cyclophosphamide and capecitabine, or the conventional paclitaxel monotherapy.
The prognosis for patients with locally advanced or metastatic disease (ABC) remains poor, with a median survival of 2-4 years. About 10% of newly diagnosed BC patients present with ABC, and 30% to 50% of patients diagnosed at earlier stages will subsequently develop metastatic disease.
In the first-line treatment of HER2 (Human Epidermal Growth factor Receptor 2) negative ABC patients, various chemotherapy regimens can be used including taxanes, which are among the most active agents in BC. Single agent response rates range from 20 to 50%. However, eventually all patients will progress with a median time to progression of 5 to 7 months. A weekly (qw) over a three-weekly (q3w) administration schedule of paclitaxel has been shown to be more effective in the metastatic as well as in the adjuvant setting after standard chemotherapy
The VEX regimen was recently investigated within a phase II trial currently ongoing at the European Institute of Oncology (IEO) (IEO number IEOS582/111; EudraCT Number: 2010-024266-21; title: "A phase II study of metronomic oral chemotherapy with cyclophosphamide plus capecitabine and vinorelbine in metastatic breast cancer patients"). Patients received vinorelbine 40 mg orally on days 1, 3 and 5 every week, cyclophosphamide 50 mg daily and capecitabine 500 mg 3 times a day.
Given the promising activity of the VEX regimen in a pre-treated population of advanced breast cancer patients and the good tolerability, the aim of the present trial is to investigate whether the VEX schedule may improve efficacy and tolerability as compared to standard paclitaxel treatment in advanced or metastatic ER-positive/HER2-negative breast cancer patients.
The concept of the VEX metronomic treatment is to administer the combination for as long as the patient has the possibility of deriving a benefit from it. The time to treatment failure (TTF) has been chosen as primary endpoint for this trial. TTF is defined as time from the date of randomization to the date when the final dose of trial treatment is administered. Chemotherapy may need to be stopped due to lack of tolerability, lack of efficacy or patient preference through subjective symptom assessment. TTF is a composite endpoint combining all these feasibility aspects of a treatment. It is therefore uniquely suited to the research question of the current trial. The secondary endpoints progression-free survival, disease control and safety will allow further assessment of the feasibility of the VEX metronomic treatment versus the paclitaxel monotherapy regimen.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A | Active Comparator | Paclitaxel 90 mg/m2 days 1, 8, 15 q4w. Patients will continue to receive assigned treatment until progression or lack of tolerability. |
|
| Arm B | Experimental | Metronomic VEX: Cyclophosphamide 50 mg orally once daily continuously, Capecitabine 500 mg, orally 3 times a day (1500 mg/day) continuously, Vinorelbine 40 mg orally days 1, 3, 5 each week continuously. Patients will continue to receive assigned treatment until progression or lack of tolerability. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Paclitaxel | Drug | Arm A |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Time to Treatment Failure (TTF) Compared Between Treatment Groups. | Efficacy and tolerability, measured by time to treatment failure, of metronomic oral vinorelbine plus cyclophosphamide and capecitabine (VEX) versus weekly paclitaxel, using an intent-to-treat analysis approach. | Assessed at the start of every 4-week (28-day) treatment cycle from randomization to the end of treatment date or discontinuation; median follow-up was 29 months, with a minimum of 0.2 months and maximum of 48.5 months. |
| Measure | Description | Time Frame |
|---|---|---|
| Frequency of Targeted Adverse Events (Safety and Tolerability). | Frequency of adverse events by type and worst grade experienced. | Time from day 1 of cycle 1 until 28 days after stopping trial treatment. |
| Disease Control |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Elisabetta Munzone, MD | European Institute of Oncology | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Centro di Riferimento Oncologico (CRO) | Aviano | Italy | ||||
| A.O.U. di Bologna Policlinico S. Orsola-Malpighi Viale Ercolani 4/2 |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 19228622 | Background | Sotiriou C, Pusztai L. Gene-expression signatures in breast cancer. N Engl J Med. 2009 Feb 19;360(8):790-800. doi: 10.1056/NEJMra0801289. No abstract available. | |
| 24126121 | Background | Senkus E, Cardoso F, Pagani O. Time for more optimism in metastatic breast cancer? Cancer Treat Rev. 2014 Mar;40(2):220-8. doi: 10.1016/j.ctrv.2013.09.015. Epub 2013 Oct 1. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm A | Paclitaxel 90 mg/m2 days 1, 8, 15 q4weeks. Patients will continue to receive assigned treatment until progression or lack of tolerability. Paclitaxel: Arm A |
| FG001 | Arm B | Metronomic VEX: Cyclophosphamide 50 mg orally once daily continuously, capecitabine 500 mg, orally 3 times a day (1500 mg/day) continuously, vinorelbine 40 mg orally days 1, 3, 5 each week continuously. Patients will continue to receive assigned treatment until progression or lack of tolerability. Cyclophosphamide: Arm B Capecitabine: Arm B Vinorelbine: Arm B |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm A | Paclitaxel 90 mg/m2 days 1, 8, 15 q4weeks. Patients continued to receive assigned treatment until objective progressive disease (PD), symptomatic deterioration, unacceptable toxicity, death, or refusal to continue treatment, whichever occurred first. Paclitaxel: Arm A |
| BG001 | Arm B |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of 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 | Time to Treatment Failure (TTF) Compared Between Treatment Groups. | Efficacy and tolerability, measured by time to treatment failure, of metronomic oral vinorelbine plus cyclophosphamide and capecitabine (VEX) versus weekly paclitaxel, using an intent-to-treat analysis approach. | Posted | Median | Standard Error | months | Assessed at the start of every 4-week (28-day) treatment cycle from randomization to the end of treatment date or discontinuation; median follow-up was 29 months, with a minimum of 0.2 months and maximum of 48.5 months. |
|
Adverse Events (AEs) were collected from the first dose of trial medication, at day 1 of every treatment cycle, until 28 days after all treatment discontinuation (end of treatment visit), regardless of whether it is considered related to a medication. In the absence of tumor progression, the patient continued to be followed for SAE reporting according and for documented disease progression or a maximum of 12 months after treatment stop, up to approximately 49 months.
AEs were collected from the first dose of trial medication until 28 days after all treatment discontinuation (EOT visit), regardless of whether it is considered related to a medication. The main criterion for tolerability is the occurrence of toxicities and adverse events. The severity and causality classified according to the NCI CTCAE Version 4.0.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arm A | Paclitaxel 90 mg/m2 days 1, 8, 15 q4weeks. Patients will continue to receive assigned treatment until progression or lack of tolerability. Paclitaxel: Arm A |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | NCI CTCAE v4.0 | Systematic Assessment | Adverse events were collected from the first dose of trial medication until 28 days after all treatment discontinuation (end of treatment visit), regardless of whether it is considered related to a medication. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | NCI CTCAE v4.0 | Systematic Assessment | Adverse events were collected from the first dose of trial medication until 28 days after all treatment discontinuation (end of treatment visit), regardless of whether it is considered related to a medication. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Heidi Roschitzki, PhD | ETOP IBCSG Partners Foundation | +41 31 511 94 00 | heidi.roschitzki@etop.ibcsg.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 19, 2017 | Nov 8, 2022 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| D009362 | Neoplasm Metastasis |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
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| ID | Term |
|---|---|
| D017239 | Paclitaxel |
| D003520 | Cyclophosphamide |
| D000069287 | Capecitabine |
| D000077235 | Vinorelbine |
| ID | Term |
|---|---|
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
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| Cyclophosphamide |
| Drug |
Arm B |
|
|
| Capecitabine | Drug | Arm B |
|
|
| Vinorelbine | Drug | Arm B |
|
|
Defined as best overall response of complete response (CR) or partial response (PR), or stable disease (SD) (or non-CR/non-PD in the case of non-measurable disease only) lasting for at least 24 weeks (at least 2 scans), measured from randomization until first documentation of progressive disease. Best overall response was defined as best response recorded from randomization across all time points until disease progression. Confirmation of partial or complete response by an additional scan was not requested in this trial. Disease response and progression were assessed according to the revised Response Evaluation Criteria in Solid Tumors (RECIST version 1.1)
| Tumor measurements were assessed at baseline, and every 12 weeks (± 2 weeks) from randomization until first disease progression on the basis of clinical and radiological tumor assessments, on average approximately 9 months. |
| Progression Free Survival (PFS) | PFS was defined as time from randomization until documented disease progression according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria or death, whichever occurred first; the death must have occurred within an interval of time corresponding to the interval of tumor re-evaluations. For patients without progression, follow-up was censored at the date of last disease assessment. | Tumor measurements were assessed at baseline, and every 12 weeks (± 2 weeks) from randomization until first disease progression on the basis of clinical and radiological tumor assessments, on average approximately 9 months. |
| Overall Survival | Overall survival from time of randomisation will be summarised for each treatment group. | From day 1 of cycle 1 until death from any cause (censored at date of last assessment of vital status for patients lost to follow up), assessed up to 36 months from the enrollment of the first patient. |
| Bologna |
| 40138 |
| Italy |
| Ospedale di Bolzano Oncologia Medica Via lorenz Bohler 5 | Bolzano | 39100 | Italy |
| Aziendale Spedali Civili di Brescia SSVD Breast Unit P.le Spedali Civili 1 | Brescia | 25123 | Italy |
| "Antonio Perrino" Division of Medical Oncology Strada Statale 7 APPIA | Brindisi | 72100 | Italy |
| Candiolo Cancer Institute (FPO-IRCCS) | Candiolo | Italy |
| ASST Di Cremona, Unità di Patologia Mammaria-Breast Unit VIALE CONCORDIA 1 | Cremona | 26100 | Italy |
| Ospedale Misericordia di Grosseto | Grosseto | Italy |
| ASST Ovest Milanese Oncology Department Via Papa Giovanni Paolo II | Legnano | Italy |
| IRST IRCCS Division of medical oncology Via Maroncelli 40 | Meldola | 47014 | Italy |
| Istituto Europeo di Oncologia, Division of Medical Senology, Via Ripamonti 435 | Milan | 20141 | Italy |
| Osp. Sacro Cuore Don Calabria Division in Medical Oncology | Negrar | Italy |
| Istituti Clinici Scientifici Maugeri SpA SB | Pavia | Italy |
| Ospedale Generale Provinciale di Macerata | Province of Macerata | Italy |
| Ospedale S. Maria delle Croci | Ravenna | Italy |
| Ospedale Infermi Uo Oncologia Via Settembrini 2 | Rimini | 47923 | Italy |
| Fondazione Policlinico Universitario A.Gemelli | Rome | Italy |
| A.O.U Città della Salute e della Scienza di Torino SSCVD Oncologia Medica Senologica (Oncology Dep.- Breast Unit) Via Cherasco 23 | Torino | 10126 | Italy |
| Asst Bg Ovest Ospedale Di Treviglio | Treviglio | Italy |
| ASST Settelaghi - Ospedale di Circolo e Fondazione Macchi U.O Oncologia Medica Viale L. Borri, 57 | Varese | 21100 | Italy |
| 16249346 | Background | Eniu A, Palmieri FM, Perez EA. Weekly administration of docetaxel and paclitaxel in metastatic or advanced breast cancer. Oncologist. 2005 Oct;10(9):665-85. doi: 10.1634/theoncologist.10-9-665. |
| 18160686 | Background | Miller K, Wang M, Gralow J, Dickler M, Cobleigh M, Perez EA, Shenkier T, Cella D, Davidson NE. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med. 2007 Dec 27;357(26):2666-76. doi: 10.1056/NEJMoa072113. |
| 20498403 | Background | Miles DW, Chan A, Dirix LY, Cortes J, Pivot X, Tomczak P, Delozier T, Sohn JH, Provencher L, Puglisi F, Harbeck N, Steger GG, Schneeweiss A, Wardley AM, Chlistalla A, Romieu G. Phase III study of bevacizumab plus docetaxel compared with placebo plus docetaxel for the first-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2010 Jul 10;28(20):3239-47. doi: 10.1200/JCO.2008.21.6457. Epub 2010 May 24. |
| 18375893 | Background | Seidman AD, Berry D, Cirrincione C, Harris L, Muss H, Marcom PK, Gipson G, Burstein H, Lake D, Shapiro CL, Ungaro P, Norton L, Winer E, Hudis C. Randomized phase III trial of weekly compared with every-3-weeks paclitaxel for metastatic breast cancer, with trastuzumab for all HER-2 overexpressors and random assignment to trastuzumab or not in HER-2 nonoverexpressors: final results of Cancer and Leukemia Group B protocol 9840. J Clin Oncol. 2008 Apr 1;26(10):1642-9. doi: 10.1200/JCO.2007.11.6699. |
| 18420499 | Background | Sparano JA, Wang M, Martino S, Jones V, Perez EA, Saphner T, Wolff AC, Sledge GW Jr, Wood WC, Davidson NE. Weekly paclitaxel in the adjuvant treatment of breast cancer. N Engl J Med. 2008 Apr 17;358(16):1663-71. doi: 10.1056/NEJMoa0707056. |
| 37440239 | Derived | Munzone E, Regan MM, Cinieri S, Montagna E, Orlando L, Shi R, Campadelli E, Gianni L, Palleschi M, Petrelli F, Bengala C, Generali D, Collova E, Puglisi F, Cretella E, Zamagni C, Chini C, Ruepp B, Loi S, Colleoni M; International Breast Cancer Study Group (IBCSG). Efficacy of Metronomic Oral Vinorelbine, Cyclophosphamide, and Capecitabine vs Weekly Intravenous Paclitaxel in Patients With Estrogen Receptor-Positive, ERBB2-Negative Metastatic Breast Cancer: Final Results From the Phase 2 METEORA-II Randomized Clinical Trial. JAMA Oncol. 2023 Sep 1;9(9):1267-1272. doi: 10.1001/jamaoncol.2023.2150. |
Metronomic VEX: Cyclophosphamide 50 mg orally once daily continuously, capecitabine 500 mg, orally 3 times a day (1500 mg/day) continuously, vinorelbine 40 mg orally days 1, 3, 5 each week continuously. Patients continued to receive assigned treatment until objective progressive disease (PD), symptomatic deterioration, unacceptable toxicity, death, or refusal to continue treatment, whichever occurred first. Cyclophosphamide: Arm B Capecitabine: Arm B Vinorelbine: Arm B |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
Metronomic VEX:
Cyclophosphamide 50 mg orally once daily continuously, Capecitabine 500 mg, orally 3 times a day (1500 mg/day) continuously, Vinorelbine 40 mg orally days 1, 3, 5 each week continuously. Patients will continue to receive assigned treatment until progression or lack of tolerability.
Cyclophosphamide: Arm B
Capecitabine: Arm B
Vinorelbine: Arm B
|
|
| Secondary | Frequency of Targeted Adverse Events (Safety and Tolerability). | Frequency of adverse events by type and worst grade experienced. | Not Posted | Time from day 1 of cycle 1 until 28 days after stopping trial treatment. | Participants |
| Secondary | Disease Control | Defined as best overall response of complete response (CR) or partial response (PR), or stable disease (SD) (or non-CR/non-PD in the case of non-measurable disease only) lasting for at least 24 weeks (at least 2 scans), measured from randomization until first documentation of progressive disease. Best overall response was defined as best response recorded from randomization across all time points until disease progression. Confirmation of partial or complete response by an additional scan was not requested in this trial. Disease response and progression were assessed according to the revised Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) | Posted | Number | participants | Tumor measurements were assessed at baseline, and every 12 weeks (± 2 weeks) from randomization until first disease progression on the basis of clinical and radiological tumor assessments, on average approximately 9 months. |
|
|
|
| Secondary | Progression Free Survival (PFS) | PFS was defined as time from randomization until documented disease progression according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria or death, whichever occurred first; the death must have occurred within an interval of time corresponding to the interval of tumor re-evaluations. For patients without progression, follow-up was censored at the date of last disease assessment. | Posted | Median | Standard Error | months | Tumor measurements were assessed at baseline, and every 12 weeks (± 2 weeks) from randomization until first disease progression on the basis of clinical and radiological tumor assessments, on average approximately 9 months. |
|
|
|
| Secondary | Overall Survival | Overall survival from time of randomisation will be summarised for each treatment group. | Posted | Median | Standard Error | months | From day 1 of cycle 1 until death from any cause (censored at date of last assessment of vital status for patients lost to follow up), assessed up to 36 months from the enrollment of the first patient. |
|
|
|
| 1 |
| 63 |
| 18 |
| 63 |
| 63 |
| 63 |
| EG001 | Arm B | Metronomic VEX: Cyclophosphamide 50 mg orally once daily continuously, capecitabine 500 mg, orally 3 times a day (1500 mg/day) continuously, vinorelbine 40 mg orally days 1, 3, 5 each week continuously. Patients will continue to receive assigned treatment until progression or lack of tolerability. Cyclophosphamide: Arm B Capecitabine: Arm B Vinorelbine: Arm B | 3 | 70 | 31 | 70 | 70 | 70 |
|
| Alopecia | Skin and subcutaneous tissue disorders | NCI CTCAE v4.0 | Systematic Assessment | Adverse events were collected from the first dose of trial medication until 28 days after all treatment discontinuation (end of treatment visit), regardless of whether it is considered related to a medication. |
|
| Palmar-plantar erythrodysesthesia syndrome | Skin and subcutaneous tissue disorders | NCI CTCAE v4.0 | Systematic Assessment | Adverse events were collected from the first dose of trial medication until 28 days after all treatment discontinuation (end of treatment visit), regardless of whether it is considered related to a medication. |
|
| Anaphylaxis | Immune system disorders | NCI CTCAE v4.0 | Systematic Assessment | Adverse events were collected from the first dose of trial medication until 28 days after all treatment discontinuation (end of treatment visit), regardless of whether it is considered related to a medication. |
|
| Allergic reaction | Immune system disorders | NCI CTCAE v4.0 | Systematic Assessment | Adverse events were collected from the first dose of trial medication until 28 days after all treatment discontinuation (end of treatment visit), regardless of whether it is considered related to a medication. |
|
| Anorexia | Metabolism and nutrition disorders | NCI CTCAE v4.0 | Systematic Assessment | Adverse events were collected from the first dose of trial medication until 28 days after all treatment discontinuation (end of treatment visit), regardless of whether it is considered related to a medication. |
|
| Diarrhea | Gastrointestinal disorders | NCI CTCAE v4.0 | Systematic Assessment | Adverse events were collected from the first dose of trial medication until 28 days after all treatment discontinuation (end of treatment visit), regardless of whether it is considered related to a medication. |
|
| Constipation | Gastrointestinal disorders | NCI CTCAE v4.0 | Systematic Assessment | Adverse events were collected from the first dose of trial medication until 28 days after all treatment discontinuation (end of treatment visit), regardless of whether it is considered related to a medication. |
|
| Mucositis oral | Gastrointestinal disorders | NCI CTCAE v4.0 | Systematic Assessment | Adverse events were collected from the first dose of trial medication until 28 days after all treatment discontinuation (end of treatment visit), regardless of whether it is considered related to a medication. |
|
| Nausea | Gastrointestinal disorders | NCI CTCAE v4.0 | Systematic Assessment | Adverse events were collected from the first dose of trial medication until 28 days after all treatment discontinuation (end of treatment visit), regardless of whether it is considered related to a medication. |
|
| Vomiting | Gastrointestinal disorders | NCI CTCAE v4.0 | Systematic Assessment | Adverse events were collected from the first dose of trial medication until 28 days after all treatment discontinuation (end of treatment visit), regardless of whether it is considered related to a medication. |
|
| Peripheral sensory neuropathy | Nervous system disorders | NCI CTCAE v4.0 | Systematic Assessment | Adverse events were collected from the first dose of trial medication until 28 days after all treatment discontinuation (end of treatment visit), regardless of whether it is considered related to a medication. |
|
| Infection | Infections and infestations | NCI CTCAE v4.0 | Systematic Assessment | Adverse events were collected from the first dose of trial medication until 28 days after all treatment discontinuation (end of treatment visit), regardless of whether it is considered related to a medication. |
|
| Arthralgia and/or myalgia | Musculoskeletal and connective tissue disorders | NCI CTCAE v4.0 | Systematic Assessment | Adverse events were collected from the first dose of trial medication until 28 days after all treatment discontinuation (end of treatment visit), regardless of whether it is considered related to a medication. |
|
| Injection site reaction | General disorders | NCI CTCAE v4.0 | Systematic Assessment | Adverse events were collected from the first dose of trial medication until 28 days after all treatment discontinuation (end of treatment visit), regardless of whether it is considered related to a medication. |
|
| Fatigue | General disorders | NCI CTCAE v4.0 | Systematic Assessment | Adverse events were collected from the first dose of trial medication until 28 days after all treatment discontinuation (end of treatment visit), regardless of whether it is considered related to a medication. |
|
| Acute coronary syndrome | Cardiac disorders | NCI CTCAE v4.0 | Systematic Assessment | Adverse events were collected from the first dose of trial medication until 28 days after all treatment discontinuation (end of treatment visit), regardless of whether it is considered related to a medication. |
|
| Left ventricular systolic dysfunction | Cardiac disorders | NCI CTCAE v4.0 | Systematic Assessment | Adverse events were collected from the first dose of trial medication until 28 days after all treatment discontinuation (end of treatment visit), regardless of whether it is considered related to a medication. |
|
| Sinus brachycardia | Cardiac disorders | NCI CTCAE v4.0 | Systematic Assessment | Adverse events were collected from the first dose of trial medication until 28 days after all treatment discontinuation (end of treatment visit), regardless of whether it is considered related to a medication. |
|
| Ventricular arrhythmia | Cardiac disorders | NCI CTCAE v4.0 | Systematic Assessment | Adverse events were collected from the first dose of trial medication until 28 days after all treatment discontinuation (end of treatment visit), regardless of whether it is considered related to a medication. |
|
| Optic nerve disorder | Nervous system disorders | NCI CTCAE v4.0 | Systematic Assessment | Adverse events were collected from the first dose of trial medication until 28 days after all treatment discontinuation (end of treatment visit), regardless of whether it is considered related to a medication. |
|
| Thrombocytopenia | Blood and lymphatic system disorders | NCI CTCAE v4.0 | Systematic Assessment | Adverse events were collected from the first dose of trial medication until 28 days after all treatment discontinuation (end of treatment visit), regardless of whether it is considered related to a medication. |
|
| Neutrophil count decreased | Blood and lymphatic system disorders | NCI CTCAE v4.0 | Systematic Assessment | Adverse events were collected from the first dose of trial medication until 28 days after all treatment discontinuation (end of treatment visit), regardless of whether it is considered related to a medication. |
|
| Aspartate aminotransferase increased | Immune system disorders | NCI CTCAE v4.0 | Systematic Assessment | Adverse events were collected from the first dose of trial medication until 28 days after all treatment discontinuation (end of treatment visit), regardless of whether it is considered related to a medication. |
|
| Pulmonary valve disease | Cardiac disorders | NCI CTCAE v4.0 | Systematic Assessment |
|
| Supraventricular tachycardia | Cardiac disorders | NCI CTCAE v4.0 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | NCI CTCAE v4.0 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | NCI CTCAE v4.0 | Systematic Assessment |
|
| Alkaline phosphatase increased | Investigations | NCI CTCAE v4.0 | Systematic Assessment |
|
| Lymphocyte count decreased | Investigations | NCI CTCAE v4.0 | Systematic Assessment |
|
| White blood cell count decreased | Investigations | NCI CTCAE v4.0 | Systematic Assessment |
|
| Hyponatremia | Metabolism and nutrition disorders | NCI CTCAE v4.0 | Systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | NCI CTCAE v4.0 | Systematic Assessment |
|
| Nail discoloration | Skin and subcutaneous tissue disorders | NCI CTCAE v4.0 | Systematic Assessment |
|
|
| Alopecia | Skin and subcutaneous tissue disorders | NCI CTCAE v4.0 | Systematic Assessment | Adverse events were collected from the first dose of trial medication until 28 days after all treatment discontinuation (end of treatment visit), regardless of whether it is considered related to a medication. |
|
| Palmar-plantar erythrodysesthesia syndrome | Skin and subcutaneous tissue disorders | NCI CTCAE v4.0 | Systematic Assessment | Adverse events were collected from the first dose of trial medication until 28 days after all treatment discontinuation (end of treatment visit), regardless of whether it is considered related to a medication. |
|
| Anaphylaxis | Immune system disorders | NCI CTCAE v4.0 | Systematic Assessment | Adverse events were collected from the first dose of trial medication until 28 days after all treatment discontinuation (end of treatment visit), regardless of whether it is considered related to a medication. |
|
| Allergic reaction | Immune system disorders | NCI CTCAE v4.0 | Systematic Assessment | Adverse events were collected from the first dose of trial medication until 28 days after all treatment discontinuation (end of treatment visit), regardless of whether it is considered related to a medication. |
|
| Anorexia | Metabolism and nutrition disorders | NCI CTCAE v4.0 | Systematic Assessment | Adverse events were collected from the first dose of trial medication until 28 days after all treatment discontinuation (end of treatment visit), regardless of whether it is considered related to a medication. |
|
| Diarrhea | Gastrointestinal disorders | NCI CTCAE v4.0 | Systematic Assessment | Adverse events were collected from the first dose of trial medication until 28 days after all treatment discontinuation (end of treatment visit), regardless of whether it is considered related to a medication. |
|
| Constipation | Gastrointestinal disorders | NCI CTCAE v4.0 | Systematic Assessment | Adverse events were collected from the first dose of trial medication until 28 days after all treatment discontinuation (end of treatment visit), regardless of whether it is considered related to a medication. |
|
| Mucositis oral | Gastrointestinal disorders | NCI CTCAE v4.0 | Systematic Assessment | Adverse events were collected from the first dose of trial medication until 28 days after all treatment discontinuation (end of treatment visit), regardless of whether it is considered related to a medication. |
|
| nausea | Gastrointestinal disorders | NCI CTCAE v4.0 | Systematic Assessment | Adverse events were collected from the first dose of trial medication until 28 days after all treatment discontinuation (end of treatment visit), regardless of whether it is considered related to a medication. |
|
| Vomiting | Gastrointestinal disorders | NCI CTCAE v4.0 | Systematic Assessment | Adverse events were collected from the first dose of trial medication until 28 days after all treatment discontinuation (end of treatment visit), regardless of whether it is considered related to a medication. |
|
| Peripheral sensory neuropathy | Nervous system disorders | NCI CTCAE v4.0 | Systematic Assessment | Adverse events were collected from the first dose of trial medication until 28 days after all treatment discontinuation (end of treatment visit), regardless of whether it is considered related to a medication. |
|
| Infection | Infections and infestations | NCI CTCAE v4.0 | Systematic Assessment | Adverse events were collected from the first dose of trial medication until 28 days after all treatment discontinuation (end of treatment visit), regardless of whether it is considered related to a medication. |
|
| Arthralgia and/or myalgia | Musculoskeletal and connective tissue disorders | NCI CTCAE v4.0 | Systematic Assessment | Adverse events were collected from the first dose of trial medication until 28 days after all treatment discontinuation (end of treatment visit), regardless of whether it is considered related to a medication. |
|
| Injection site reaction | General disorders | NCI CTCAE v4.0 | Systematic Assessment | Adverse events were collected from the first dose of trial medication until 28 days after all treatment discontinuation (end of treatment visit), regardless of whether it is considered related to a medication. |
|
| Fatigue | General disorders | NCI CTCAE v4.0 | Systematic Assessment | Adverse events were collected from the first dose of trial medication until 28 days after all treatment discontinuation (end of treatment visit), regardless of whether it is considered related to a medication. |
|
| Acute coronary syndrome | Cardiac disorders | NCI CTCAE v4.0 | Systematic Assessment | Adverse events were collected from the first dose of trial medication until 28 days after all treatment discontinuation (end of treatment visit), regardless of whether it is considered related to a medication. |
|
| Left ventricular systolic dysfunction | Cardiac disorders | NCI CTCAE v4.0 | Systematic Assessment | Adverse events were collected from the first dose of trial medication until 28 days after all treatment discontinuation (end of treatment visit), regardless of whether it is considered related to a medication. |
|
| Sinus brachycardia | Cardiac disorders | NCI CTCAE v4.0 | Systematic Assessment | Adverse events were collected from the first dose of trial medication until 28 days after all treatment discontinuation (end of treatment visit), regardless of whether it is considered related to a medication. |
|
| Supraventricular tachycardia | Cardiac disorders | NCI CTCAE v4.0 | Systematic Assessment | Adverse events were collected from the first dose of trial medication until 28 days after all treatment discontinuation (end of treatment visit), regardless of whether it is considered related to a medication. |
|
| Ventricular arrhythmia | Cardiac disorders | NCI CTCAE v4.0 | Systematic Assessment | Adverse events were collected from the first dose of trial medication until 28 days after all treatment discontinuation (end of treatment visit), regardless of whether it is considered related to a medication. |
|
| Optic nerve disorder | Nervous system disorders | NCI CTCAE v4.0 | Systematic Assessment | Adverse events were collected from the first dose of trial medication until 28 days after all treatment discontinuation (end of treatment visit), regardless of whether it is considered related to a medication. |
|
| Thrombocytopenia | Blood and lymphatic system disorders | NCI CTCAE v4.0 | Systematic Assessment | Adverse events were collected from the first dose of trial medication until 28 days after all treatment discontinuation (end of treatment visit), regardless of whether it is considered related to a medication. |
|
| Neutrophil count decreased | Blood and lymphatic system disorders | NCI CTCAE v4.0 | Systematic Assessment | Adverse events were collected from the first dose of trial medication until 28 days after all treatment discontinuation (end of treatment visit), regardless of whether it is considered related to a medication. |
|
| Asparate aminotransferase increased | Immune system disorders | NCI CTCAE v4.0 | Systematic Assessment | Adverse events were collected from the first dose of trial medication until 28 days after all treatment discontinuation (end of treatment visit), regardless of whether it is considered related to a medication. |
|
| Aortic valve disease | Cardiac disorders | NCI CTCAE v4.0 | Systematic Assessment |
|
| Atrial flutter | Cardiac disorders | NCI CTCAE v4.0 | Systematic Assessment |
|
| Cataract | Eye disorders | NCI CTCAE v4.0 | Systematic Assessment |
|
| Ascites | Gastrointestinal disorders | NCI CTCAE v4.0 | Systematic Assessment |
|
| Sudden death, not otherwise specified | General disorders | NCI CTCAE v4.0 | Systematic Assessment |
|
| Fracture | Injury, poisoning and procedural complications | NCI CTCAE v4.0 | Systematic Assessment |
|
| Hip fracture | Injury, poisoning and procedural complications | NCI CTCAE v4.0 | Systematic Assessment |
|
| Alkaline phosphatase increased | Investigations | NCI CTCAE v4.0 | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | NCI CTCAE v4.0 | Systematic Assessment |
|
| GGT increased | Investigations | NCI CTCAE v4.0 | Systematic Assessment |
|
| Hyperglycemia | Metabolism and nutrition disorders | NCI CTCAE v4.0 | Systematic Assessment |
|
| Hyponatremia | Metabolism and nutrition disorders | NCI CTCAE v4.0 | Systematic Assessment |
|
| Depressed level of consciousness | Nervous system disorders | NCI CTCAE v4.0 | Systematic Assessment |
|
| Facial nerve disorder | Nervous system disorders | NCI CTCAE v4.0 | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | NCI CTCAE v4.0 | Systematic Assessment |
|
| Pulmonary edema | Respiratory, thoracic and mediastinal disorders | NCI CTCAE v4.0 | Systematic Assessment |
|
| Respiratory, thoracic and mediastinal disorders - Other, specify | Respiratory, thoracic and mediastinal disorders | NCI CTCAE v4.0 | Systematic Assessment |
|
| Hypotension | Vascular disorders | NCI CTCAE v4.0 | Systematic Assessment |
|
Not provided
Not provided
| D017437 |
| Skin and Connective Tissue Diseases |
| D009385 | Neoplastic Processes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006844 |
| Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D005472 | Fluorouracil |
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D003853 | Deoxyribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D014748 | Vinca Alkaloids |
| D046948 | Secologanin Tryptamine Alkaloids |
| D026121 | Indole Alkaloids |
| D000470 | Alkaloids |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D054836 | Indolizidines |
| D007212 | Indolizines |
| Stable disease (SD)/non-complete response (CR)/non-progressive disease (PD) |
|
| Progressive disease (PD) |
|
| Not evaluable (NE) |
|