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| ID | Type | Description | Link |
|---|---|---|---|
| 2011-002843-92 | EudraCT Number |
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The purpose of this phase III study is to determine whether Doxorubicin Transdrug (DT) is effective in the treatment of patients suffering from advanced Hepatocellular Carcinoma (HCC) after failure or intolerance to Sorafenib. Patients with HCC with or without cirrhosis and with good liver functions are eligible. Only those who can not benefit from treatment for which efficacy is demonstrated are eligible.
These patients are usually proposed either best standard of care (BSC) or participation to clinical trials. Patients eligible for the RELIVE study will receive either DT at 20 mg/m2 or DT at 30 mg/m2 or the BSC.
Doxorubicin-Transdrugâ„¢ (DT) is a nanoparticle formulation of doxorubicin.In in vitro and in vivo models, DT was shown to overcome the multidrug resistance (MDR) and to be more effective than doxorubicin on both sensitive and resistant tumour models and in particular in the X/myc bi-transgenic MDR murine model of HCC.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Doxorubicin Transdrug (DT) at 20 mg/m2 | Experimental | DT will be infused over 6 hours through the intravenous (IV) route at dose of 20 mg/m2 on Day 1 and will be repeated every 4 weeks until disease progression or unacceptable toxicity |
|
| Doxorubicin Transdrug (DT) at 30 mg/m2 | Experimental | DT will be infused over 6 hours through the IV route at dose of 30 mg/m2 on Day 1 and will be repeated every 4 weeks until disease progression or unacceptable toxicity |
|
| Best Standard of Care | Active Comparator | Patients randomized in the control group will receive treatment according to the investigator's choice, until disease progression or unacceptable toxicity |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Doxorubicin 20 mg/m2 | Drug |
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| |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival (OS) | OS is defined as the time from date of randomization to the date of death from any cause. | Time from date of randomization to the date of death from any cause with initial assessment up to 24 months and follow-up assessment up to 45 months. |
| Measure | Description | Time Frame |
|---|---|---|
| Progression-free Survival (PFS) | PFS is defined as time from the date of randomisation to the date of the first documented progression or death from any cause. PFS determined by independent radiological review according to Response Evaluation Criteria In Solid Tumour (RECIST) 1.1 is determine by at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is considered progression. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) Considered Related to Treatment Categorized by Severity, Withdrawal From Study, or Death | The number of participants experiencing TEAEs considered related to treatment and categorized by severity of all related TEAEs according to National Cancer Institute/Common Toxicity Criteria (NCI-CTCAE) v4.0 and resulting in patient withdrawal from study or death. |
Inclusion Criteria:
Male or non-pregnant, non-breast feeding female;
Aged ≥ 18 years;
Patient with:
Patients with porta hepatis lymph nodes, extrahepatic metastases, or portal/suprahepatic vein thrombosis without extension in inferior/superior vena cava, are eligible;
HCC diagnosed according to the American Association for Study of Liver Diseases (AASLD) and/or European Association for the Study of the Liver (EASL) criteria:
Nodule ≥ 10 mm: one imaging technique among MRI and CT-scan showing typical appearances for HCC defined as arterial enhancement and rapid washout in portal venous or delayed phase;
If appearance not typical for HCC on initial imaging: second contrast enhanced study (CT or MRI) showing typical appearances for HCC defined as arterial enhancement and rapid wash-out in portal venous or delayed phase;
Without cirrhosis or with a non decompensated cirrhosis (Child-Pugh score from A5 to B7 included);
Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1;
Laboratory tests as follows:
Signed and dated written informed consent form.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Philippe Merle, MD | Croix-Rousse Hospital - Lyon-France | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Gabrail Cancer Center | Canton | Ohio | 44718 | United States | ||
| Penn State Hershey Cancer Institute |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30954567 | Derived | Merle P, Blanc JF, Phelip JM, Pelletier G, Bronowicki JP, Touchefeu Y, Pageaux G, Gerolami R, Habersetzer F, Nguyen-Khac E, Casadei-Gardini A, Borbath I, Tran A, Wege H, Saad AS, Colombo M, Abergel A, Richou C, Waked I, Yee NS, Mole A, Attali P, Le Boulicaut J, Vasseur B; RELIVE Investigators. Doxorubicin-loaded nanoparticles for patients with advanced hepatocellular carcinoma after sorafenib treatment failure (RELIVE): a phase 3 randomised controlled trial. Lancet Gastroenterol Hepatol. 2019 Jun;4(6):454-465. doi: 10.1016/S2468-1253(19)30040-8. Epub 2019 Apr 4. |
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Of the 144 patients who failed screening, the most common reason for screen failure was meeting liver function exclusion criteria.
A total of 541 patients were screened, and 397 patients were randomized a 1:1:1 allocation at 69 sites in 11 countries worldwide. The randomization was performed using an interactive web response system (IWRS) with stratification based on region.
Enrollment of first patient was June 15, 2012. Data cutoff was May 28, 2017 (24 months) for initial study and May 10, 2019, for follow-up period (45 months).
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| ID | Title | Description |
|---|---|---|
| FG000 | Doxorubicin Transdrug (DT) at 20 mg/m2 | DT was infused over 6 hours through the intravenous (IV) route at dose of 20 mg/m2 on Day 1 and was repeated every 4 weeks until disease progression or unacceptable toxicity. |
| FG001 | Doxorubicin Transdrug at 30 mg/m2 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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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 | Jul 27, 2017 |
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| Doxorubicin 30 mg/m2 |
| Drug |
|
|
| Best Standard of Care | Drug |
|
|
| Time from date of randomization to date of first documented progression or death from any cause, which ever came first, assessed up to 20 months. |
| Objective Response Rate (ORR) | ORR is defined as percent of patients whose best overall response is complete response (CR) or partial response (PR) during the study treatment period and based on the evaluation of independent radiological review according to RECIST 1.1 for target lesions and assessed by MRI: CR is disappearance of all targets extra nodal lesions and the regression of all nodal lesions to < 10 mm; PR is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; stable disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum of diameters while on study. PD is at least a 20% increase in the sum of diameters of target lesions, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is considered progression. | Time from date of first treatment cycle to date of last cycle of treatment for the full duration of study treatment up to 24 months. |
| Time from date of initial treatment to date of death, disease progression, or participant withdrawal from the study. |
| Number of Participants With Cardiovascular and Respiratory Events Related to Study Drug | The number of participants with cardiovascular and respiratory adverse events (AEs) were assessed according to National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) criteria version 4.0, using the Medical Dictionary for Regulatory Activities (MedDRA). The AE numbers reported are those considered related to treatment. Related AEs are those that are judged unlikely, possibly, probably or definitely related to the study or study drug by the investigator. | Time from date of initial treatment to date of death, disease progression, or patient withdrawal from the study. |
| Number of Participants Experiencing a Reduction of Oxygen Saturation (SaO2) During and After Doxorubicin Transdrug (DT) Infusion | Number of participants experiencing an SaO2 reduction defined as a decrease =< 90% during or after DT infusion until resolution to =>93%. Participants had continuous monitoring of SaO2 saturation with pulse oximeter during 6 hour infusion and up to 24 hour after infusion start. SaO2 measures the amount of oxygen (in percent) bound to hemoglobin in red blood cells. SaO2 saturation was only monitored and reported in the DT infusion group. Reduction in SaO2 could result in modify DT dosing regimen. Decreases in SaO2 are a known and expected occurrence with DT infusions, and close monitoring of SaO2 was specified by the protocol to protect patients from potential respiratory distress during infusions. | Time from start of infusion to resolution of reduction in oxygen saturation. |
| Number of Participants With Clinically Significant Abnormal Change in Respiratory Function | Number of participants with any clinically significant abnormal change in respiratory function test over the study to include carbon monoxide diffusing capacity to measure lung function, forced expiratory volume in 1 second to measure ability to expel air from your lungs, total lung capacity to measure total amount of air in the lungs after taking the deepest breath possible, and vital capacity to measure the greatest volume of air that can be expelled from the lungs after taking the deepest breath possible. Clinically significant abnormal changes in respiratory function was determined by the investigator. | Time from baseline assessment to time of death, disease progression, or withdrawal of patient from the study. |
| Number of Participants Experiencing Clinically Significant Abnormal Electrocardiogram (ECG) Changes From Baseline | Number of participants experiencing clinically significant abnormal ECG changes from baseline over the course of the study. ECG were completed every month before each infusion. ECG will detect changes in heart rhythm. Clinically significant abnormal changes in ECG were determined by the investigator. | Time from baseline assessment to time of death, disease progression, or withdrawal of patient from the study. |
| Number of Participants Experiencing Clinically Significant Changes in Left Ventricular Ejection Fraction (LVEF) and the Severity of the Event | Number of participants that experienced a change from baseline in LVEF with severity of LVEF noted as follows: Normal: 100 - 50%, 0 - 9% drop from baseline resting ejection fraction (EF), Grade 2 = 50 - 40%, 10 - 19% drop from baseline resting EF; Grade 3 = 39 - 20%, >20% drop from baseline; Grade 4 = <20%. LVEF was monitored every other month. LVEF measures how much blood the left ventricle of the heart pumps out with each contraction and is used to assess the severity of left ventricle dysfunction in the heart. Clinical significance changes were determined by the investigator. | Time from baseline assessment to time of death, disease progression, or withdrawal of patient from the study. |
| Hershey |
| Pennsylvania |
| 17033 |
| United States |
| Allegheny General Hospital | Pittsburgh | Pennsylvania | 15212 | United States |
| Krankenhaus der Elisabethinen Linz GmbH | Linz | 4020 | Austria |
| Medical University Vienna | Vienna | 1090 | Austria |
| CHU Brugmann | Brussels | 1020 | Belgium |
| UCL Saint-Luc | Brussels | 1200 | Belgium |
| CHU Sart Tilman | Liège | 4000 | Belgium |
| CHU UCL Mont-Godinne Dinant | Yvoir | Belgium |
| Medical Oncology department /Mansoura University Hospitals | Al Mansurah | 35516 | Egypt |
| Clinical Research Center/ Alexandria university hospital | Alexandria | Egypt |
| Oncology Department, Medical Research Institute, Alexandria University | Alexandria | Egypt |
| Medical Oncology department /Ain Shams University Hospitals | Cairo | Egypt |
| National hepatology and tropical medicine research institute | Cairo | Egypt |
| National Liver Institute / Menoufyia University | Menofia | 32700 | Egypt |
| Hospital Amiens | Amiens | 80054 | France |
| Hospital Jean Minjoz | Besançon | 25000 | France |
| Hospital Saint André | Bordeaux | 33075 | France |
| Centre hospitalier P Oudot | Bourgoin | 38302 | France |
| Hospital Estaing | Clermont-Ferrand | 63003 | France |
| Centre Hospitalier Beaujon | Clichy | 92110 | France |
| Hospital Henri-Mondor | Créteil | 94010 | France |
| Centre Jean-François Leclerc | Dijon | 21079 | France |
| CHU | Dijon | France |
| Hospital Grenoble | La Tronche | 38700 | France |
| CHU Dupuytren | Limoges | 87042 | France |
| Hospital Croix Rousse | Lyon | 69317 | France |
| Hospital La Timone | Marseille | 13005 | France |
| Hospital Saint Eloi | Montpellier | 34295 | France |
| Hospital Brabois | Nancy | 54511 | France |
| Hospital Hotel Dieu | Nantes | 44093 | France |
| CHU - Hôpital Archet | Nice | France |
| Hospital La Source | Orléans | 45067 | France |
| Hospital Pitié-Salpetriere | Paris | 75013 | France |
| Hospital Tenon | Paris | 75020 | France |
| Hospital Saint Jean | Perpignan | 66046 | France |
| CHU de Rouen- Hôpital Charles Nicolle | Rouen | 76031 | France |
| IC LOIRE | Saint-Etienne | France |
| Hospital Civil | Strasbourg | 67091 | France |
| Hospital Paul Brousse | Villejuif | 94804 | France |
| Universitätsklinikum Freiburg | Freiburg im Breisgau | 79106 | Germany |
| Universitätsklinikum Halle (Saale) | Halle | 06120 | Germany |
| Universitätsklinikum Hamburg-Eppendorf | Hamburg | 20246 | Germany |
| Universität Leipzig AöR | Leipzig | 04103 | Germany |
| Klinikum rechts der Isar der TU Munchen II | München | 81675 | Germany |
| Semmelweis Egyetem Radiológiai és Onkoterápiás Klinika | Budapest | 1082 | Hungary |
| EgyesÃtett Szent István és Szent László Kórház - RendelÅ‘intézet | Budapest | 1097 | Hungary |
| Debreceni Egyetem Orvos- és Egészségtudományi Centrum Onkológiai Intézet | Debrecen | 4032 | Hungary |
| Szegedi Tudományegyetem Onkoterápiás Klinika | Szeged | 6720 | Hungary |
| Irccs Centro Di Riferimento Oncologico (Cro) | Aviano | 33081 | Italy |
| Ospedale Civile e degli Infermi | Faenza | 48018 | Italy |
| Ausl 12 Livorno Ospedale Unico della Versilia | Lido di Camaiore | 55041 | Italy |
| IRST Istituto Romagnolo Ricerca e Cura dei Tumori | Meldola | 47014 | Italy |
| Granda Osp. Magg. Policlinico | Milan | 20122 | Italy |
| Azienda Ospedaliera Policlinico di Modena | Modena | 41124 | Italy |
| A.O. Ospedale Maggiore della Carità | Novara | 28100 | Italy |
| Rimini | 47900 | Italy |
| Ain Wazein Hospital | El Chouf | Lebanon |
| Hospital General Universitario de Alicante | Alicante | 03010 | Spain |
| Hospital Universitario Virgen de la Arrixaca | El Palmar Murcia | 30120 | Spain |
| Complejo Hospitalario de Jaen | Jaén | 23006 | Spain |
| Hospital General Universario Gregorio Maranon | Madrid | 28007 | Spain |
| Hospital Universitario Ramón y Cajal | Madrid | 28034 | Spain |
| Hospital Universitario Madrid Sanchinarro | Madrid | 28050 | Spain |
| Hospital Carlos Haya | Málaga | 29010 | Spain |
| Hospital Universario Son Espaces | Palma de Mallorca | 07010 | Spain |
| Hospital Universitario Marques de Valdecilla | Santander | 39008 | Spain |
| Hospital Universitario RÃo Hortega | Valladolid | 47012 | Spain |
| Hacettepe University Medical Faculty | Ankara | Turkey (Türkiye) |
| Ege Univeristy Medical Faculty, | Izmir | Turkey (Türkiye) |
DT was infused over 6 hours through the IV route at dose of 30 mg/m2 on Day 1 and was repeated every 4 weeks until disease progression or unacceptable toxicity. |
| FG002 | Best Standard of Care | Patients randomized in the control group received treatment according to the investigator's choice, until disease progression or unacceptable toxicity. |
| COMPLETED |
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| NOT COMPLETED |
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Intent-to-Treat population: all randomized patients.
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| ID | Title | Description |
|---|---|---|
| BG000 | Doxorubicin Transdrug (DT) at 20 mg/m2 | DT was infused over 6 hours through the intravenous (IV) route at dose of 20 mg/m2 on Day 1 and was repeated every 4 weeks until disease progression or unacceptable toxicity. |
| BG001 | Doxorubicin Transdrug at 30 mg/m2 | DT was infused over 6 hours through the IV route at dose of 30 mg/m2 on Day 1 and was repeated every 4 weeks until disease progression or unacceptable toxicity. |
| BG002 | Best Standard of Care | Patients randomized in the control group received treatment according to the investigator's choice, until disease progression or unacceptable toxicity. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| Alcohol Consumption | Count of Participants | Participants |
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| Child Pugh Class | The Child-Pugh score is determined by scoring five clinical measures of liver disease: encephalopathy, ascites, albumin, total bilirubin, prothrombin time rate. A score of 1, 2, or 3 is given to each measure, with 3 being the most severe. The total score is used to assign the Child-Pugh class as follows: Class A: 5-6 points (least severe liver disease) Class B: 7-9 points (moderately severe liver disease) Class C: 10-15 points (most severe liver disease) | Count of Participants | Participants |
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| Previous Hepatocellular Carcinoma (HCC) Treatments | Prior treatment for HCC is collected at baseline as part of the medical history for surgery and the following drugs and therapy: sorafenib, hormone therapy, tyrosine kinase inhibitor, investigational drug, cytotoxic chemotherapy, and other anticancer therapy. Patients may have received treatment in more than one of these categories. | Count of Participants | Participants |
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| Medical History Active | Active medical history of patient at time of baseline assessment is collected. Presenting all active medical history that occurred at an incidence of >=10% of the patients in at least one of the treatment groups is presented for all groups. Patients may fall into more than one of these categories. | Count of Participants | Participants |
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| HCC History-Cirrhosis | Count of Participants | Participants |
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| HCC History - Cyto Histology | Used American Association for the Study of Liver Diseases (AASLD)/European Association for the Study of the Liver (EASL) Criteria | Count of Participants | Participants |
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| HCC History - Macroscopic Vascular Invasion | Multiple selection possible for vascular invasion. | Count of Participants | Participants |
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| HCC History - Extra Hepatic Spread - Porta Hepatic Lymph Nodes | Count of Participants | Participants |
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| HCC History - Extra Hepatic Spread - Distant Metastases | Count of Participants | Participants |
| ||||||||||||||||
| HCC History - Aetiology of Underlying Liver Disease | Percentages are based on the number of patients in the respective group. Patients could have more than one aetiology of underlying liver disease and may be counted in more than one category. | Count of Participants | Participants |
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| HCC History - Nodule in the Liver | Count of Participants | Participants |
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| HCC History - Disease Duration | Disease duration is calculated at study entry in months as the screening visit date - cancer diagnosis date. | Mean | Standard Deviation | months |
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| 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 | Overall Survival (OS) | OS is defined as the time from date of randomization to the date of death from any cause. | Intent-to-treat (ITT) Population: All randomized patients. The DT at 20 mg/m2 and 30 mg/m2 are combined into DT pooled experimental group for comparison with the BSC group. The primary analysis per protocol is DT pooled versus BSC and not individual DT groups. | Posted | Median | 95% Confidence Interval | months | Time from date of randomization to the date of death from any cause with initial assessment up to 24 months and follow-up assessment up to 45 months. |
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| Secondary | Progression-free Survival (PFS) | PFS is defined as time from the date of randomisation to the date of the first documented progression or death from any cause. PFS determined by independent radiological review according to Response Evaluation Criteria In Solid Tumour (RECIST) 1.1 is determine by at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is considered progression. | ITT population: All randomized patients. The DT at 20 mg/m2 and 30 mg/m2 are combined into DT pooled experimental group for comparison with the BSC group. The primary analysis is DT pooled versus BSC. This was only analyzed for the initial study. | Posted | Median | 95% Confidence Interval | months | Time from date of randomization to date of first documented progression or death from any cause, which ever came first, assessed up to 20 months. |
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| Secondary | Objective Response Rate (ORR) | ORR is defined as percent of patients whose best overall response is complete response (CR) or partial response (PR) during the study treatment period and based on the evaluation of independent radiological review according to RECIST 1.1 for target lesions and assessed by MRI: CR is disappearance of all targets extra nodal lesions and the regression of all nodal lesions to < 10 mm; PR is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; stable disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum of diameters while on study. PD is at least a 20% increase in the sum of diameters of target lesions, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is considered progression. | ITT population: all randomized patients. The DT at 20 mg/m2 and 30 mg/m2 are combined into DT pooled experimental group for comparison with the BSC group. The primary analysis is the DT pooled versus BCS. This was only analyzed for the initial study. | Posted | Count of Participants | Participants | Time from date of first treatment cycle to date of last cycle of treatment for the full duration of study treatment up to 24 months. |
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| Other Pre-specified | Number of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) Considered Related to Treatment Categorized by Severity, Withdrawal From Study, or Death | The number of participants experiencing TEAEs considered related to treatment and categorized by severity of all related TEAEs according to National Cancer Institute/Common Toxicity Criteria (NCI-CTCAE) v4.0 and resulting in patient withdrawal from study or death. | Safety Population: All patients receiving at least one infusion for DT groups and all patients for BSC group whatever treatment they received. | Posted | Count of Participants | Participants | Time from date of initial treatment to date of death, disease progression, or participant withdrawal from the study. |
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| Other Pre-specified | Number of Participants With Cardiovascular and Respiratory Events Related to Study Drug | The number of participants with cardiovascular and respiratory adverse events (AEs) were assessed according to National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) criteria version 4.0, using the Medical Dictionary for Regulatory Activities (MedDRA). The AE numbers reported are those considered related to treatment. Related AEs are those that are judged unlikely, possibly, probably or definitely related to the study or study drug by the investigator. | Safety Population: All patients receiving at least one infusion for DT groups and all patients for BSC group whatever treatment they received. | Posted | Count of Participants | Participants | Time from date of initial treatment to date of death, disease progression, or patient withdrawal from the study. |
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| Other Pre-specified | Number of Participants Experiencing a Reduction of Oxygen Saturation (SaO2) During and After Doxorubicin Transdrug (DT) Infusion | Number of participants experiencing an SaO2 reduction defined as a decrease =< 90% during or after DT infusion until resolution to =>93%. Participants had continuous monitoring of SaO2 saturation with pulse oximeter during 6 hour infusion and up to 24 hour after infusion start. SaO2 measures the amount of oxygen (in percent) bound to hemoglobin in red blood cells. SaO2 saturation was only monitored and reported in the DT infusion group. Reduction in SaO2 could result in modify DT dosing regimen. Decreases in SaO2 are a known and expected occurrence with DT infusions, and close monitoring of SaO2 was specified by the protocol to protect patients from potential respiratory distress during infusions. | Safety population: All patients receiving at least one infusion for DT groups. | Posted | Count of Participants | Participants | Time from start of infusion to resolution of reduction in oxygen saturation. |
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| Other Pre-specified | Number of Participants With Clinically Significant Abnormal Change in Respiratory Function | Number of participants with any clinically significant abnormal change in respiratory function test over the study to include carbon monoxide diffusing capacity to measure lung function, forced expiratory volume in 1 second to measure ability to expel air from your lungs, total lung capacity to measure total amount of air in the lungs after taking the deepest breath possible, and vital capacity to measure the greatest volume of air that can be expelled from the lungs after taking the deepest breath possible. Clinically significant abnormal changes in respiratory function was determined by the investigator. | Safety Population: All patients receiving at least one infusion for DT groups and all patients for BSC group whatever treatment they received. | Posted | Count of Participants | Participants | Time from baseline assessment to time of death, disease progression, or withdrawal of patient from the study. |
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| Other Pre-specified | Number of Participants Experiencing Clinically Significant Abnormal Electrocardiogram (ECG) Changes From Baseline | Number of participants experiencing clinically significant abnormal ECG changes from baseline over the course of the study. ECG were completed every month before each infusion. ECG will detect changes in heart rhythm. Clinically significant abnormal changes in ECG were determined by the investigator. | Safety Population: All patients receiving at least one infusion for DT groups and all patients for BSC group whatever treatment they received. | Posted | Count of Participants | Participants | Time from baseline assessment to time of death, disease progression, or withdrawal of patient from the study. |
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| Other Pre-specified | Number of Participants Experiencing Clinically Significant Changes in Left Ventricular Ejection Fraction (LVEF) and the Severity of the Event | Number of participants that experienced a change from baseline in LVEF with severity of LVEF noted as follows: Normal: 100 - 50%, 0 - 9% drop from baseline resting ejection fraction (EF), Grade 2 = 50 - 40%, 10 - 19% drop from baseline resting EF; Grade 3 = 39 - 20%, >20% drop from baseline; Grade 4 = <20%. LVEF was monitored every other month. LVEF measures how much blood the left ventricle of the heart pumps out with each contraction and is used to assess the severity of left ventricle dysfunction in the heart. Clinical significance changes were determined by the investigator. | Safety Population: All patients receiving at least one infusion for DT groups and all patients for BSC group whatever treatment they received. | Posted | Count of Participants | Participants | Time from baseline assessment to time of death, disease progression, or withdrawal of patient from the study. |
|
Adverse events (AEs) were collected until 1 month after last treatment. Treatment continued until patient experienced disease progression, aggravation of liver dysfunction, death, serious AE (SAE), or intolerable AE; or the patient withdrew consent or was withdrawn from study by investigator for reasons listed in the protocol. Median treatment durations were 1.9, 2.7, and 2.4 months in the Doxorubicin Transdrug (DT) 20 mg/m2, DT 30 mg/m2, and best standard of care (BSC) groups, respectively.
The incidence and severity of all AEs and SAEs were assessed according to National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) criteria version 4.0, using the Medical Dictionary for Regulatory Activities (MedDRA). The cutoff for AE reporting was May 28, 2017.
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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 | Doxorubicin Transdrug (DT) at 20 mg/m2 | DT was infused over 6 hours through the intravenous (IV) route at dose of 20 mg/m2 on Day 1 and was repeated every 4 weeks until disease progression or unacceptable toxicity. | 118 | 122 | 37 | 122 | 110 | 122 |
| EG001 | Doxorubicin Transdrug at 30 mg/m2 | DT was infused over 6 hours through the IV route at dose of 30 mg/m2 on Day 1 and was repeated every 4 weeks until disease progression or unacceptable toxicity. | 119 | 120 | 37 | 120 | 112 | 120 |
| EG002 | Best Standard of Care | Patients randomized in the control group received treatment according to the investigator's choice, until disease progression or unacceptable toxicity. | 113 | 134 | 48 | 134 | 97 | 134 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Catheter site infection | Infections and infestations | MedDRA (19.0) | Non-systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (19.0) | Non-systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA (19.0) | Non-systematic Assessment |
| |
| Endocarditis | Infections and infestations | MedDRA (19.0) | Non-systematic Assessment |
| |
| Escherichia sepsis | Infections and infestations | MedDRA (19.0) | Non-systematic Assessment |
| |
| Liver abscess | Infections and infestations | MedDRA (19.0) | Non-systematic Assessment |
| |
| Lower respiratory tract infection | Infections and infestations | MedDRA (19.0) | Non-systematic Assessment |
| |
| Lung infection | Infections and infestations | MedDRA (19.0) | Non-systematic Assessment |
| |
| Septic shock | Infections and infestations | MedDRA (19.0) | Non-systematic Assessment |
| |
| Staphylococcal sepsis | Infections and infestations | MedDRA (19.0) | Non-systematic Assessment |
| |
| Subcutaneous abscess | Infections and infestations | MedDRA (19.0) | Non-systematic Assessment |
| |
| Ascites | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Peritoneal haemorrhage | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Melaena | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| General physical health deterioration | General disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Chills | General disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Mucosal inflammation | General disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Oedema | General disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Acute pulmonary oedema | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Bronchopneumopathy | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Interstitial lung disease | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Restrictive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Atrioventricular block complete | Cardiac disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Atrioventricular block second degree | Cardiac disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Cardiac failure | Cardiac disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Ischaemic cardiomyopathy | Cardiac disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Hepatic encephalopathy | Hepatobiliary disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Oxygen saturation decreased | Investigations | MedDRA (19.0) | Non-systematic Assessment |
| |
| N-terminal prohormone brain natriuretic peptide increased | Investigations | MedDRA (19.0) | Non-systematic Assessment |
| |
| Respiratory rate decreased | Investigations | MedDRA (19.0) | Non-systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Proteinuria | Renal and urinary disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Drug hypersensitivity | Immune system disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Osteitis | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Tumour haemorrhage | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (19.0) | Non-systematic Assessment |
| |
| Oesophageal varices haemorrhage | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Upper gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Haematemesis | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Peptic ulcer haemorrhage | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Retroperitoneal haematoma | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Asthenia | General disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Pain | General disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Complications associated with device | General disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Generalised oedema | General disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Hypothermia | General disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Multiple organ dysfunction syndrome | General disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Hepatic failure | Hepatobiliary disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Hepatorenal syndrome | Hepatobiliary disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Portal vein thrombosis | Hepatobiliary disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Biliary dilatation | Hepatobiliary disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Cholelithiasis | Hepatobiliary disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Coma hepatic | Hepatobiliary disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Jaundice | Hepatobiliary disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Peritonitis | Infections and infestations | MedDRA (19.0) | Non-systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (19.0) | Non-systematic Assessment |
| |
| Campylobacter infection | Infections and infestations | MedDRA (19.0) | Non-systematic Assessment |
| |
| Enterobacter pneumonia | Infections and infestations | MedDRA (19.0) | Non-systematic Assessment |
| |
| Erysipelas | Infections and infestations | MedDRA (19.0) | Non-systematic Assessment |
| |
| Peritonitis bacterial | Infections and infestations | MedDRA (19.0) | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Lung disorder | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Malignant neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (19.0) | Non-systematic Assessment |
| |
| Lung neoplasm malignant | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (19.0) | Non-systematic Assessment |
| |
| Metastases to adrenals | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (19.0) | Non-systematic Assessment |
| |
| Metastases to bone | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (19.0) | Non-systematic Assessment |
| |
| Metastases to central nervous system | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (19.0) | Non-systematic Assessment |
| |
| Neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (19.0) | Non-systematic Assessment |
| |
| Peritumoural oedema | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (19.0) | Non-systematic Assessment |
| |
| Squamous cell carcinoma of lung | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (19.0) | Non-systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Trismus | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Supraventricular tachycardia | Cardiac disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Atrial thrombosis | Cardiac disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Arterial occlusive disease | Vascular disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Superior vena cava syndrome | Vascular disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Vena cava thrombosis | Vascular disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Femur fracture | Injury, poisoning and procedural complications | MedDRA (19.0) | Non-systematic Assessment |
| |
| Lumbar vertebral fracture | Injury, poisoning and procedural complications | MedDRA (19.0) | Non-systematic Assessment |
| |
| Post procedural bile leak | Injury, poisoning and procedural complications | MedDRA (19.0) | Non-systematic Assessment |
| |
| Spinal fracture | Injury, poisoning and procedural complications | MedDRA (19.0) | Non-systematic Assessment |
| |
| Completed suicide | Psychiatric disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Mental status changes | Psychiatric disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Cerebral haematoma | Nervous system disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Neuralgia | Nervous system disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Skin ulcer | Skin and subcutaneous tissue disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Venous ulcer pain | Skin and subcutaneous tissue disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Impaired quality of life | Social circumstances | MedDRA (19.0) | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Asthenia | General disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Neuropathy peripheral | Nervous system disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Decreased Appetite | Metabolism and nutrition disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Mucosal inflammation | General disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA (19.0) | Non-systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA (19.0) | Non-systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA (19.0) | Non-systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA (19.0) | Non-systematic Assessment |
| |
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Jaundice | Hepatobiliary disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA (19.0) | Non-systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Olivier De Beaumont; Chief Medical Officer | ONXEO | +33 (0) 1 45 58 95 33 | o.debeaumont@onxeo.com |
| Nov 12, 2020 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D006528 | Carcinoma, Hepatocellular |
| ID | Term |
|---|---|
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008113 | Liver Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D004066 | Digestive System Diseases |
| D008107 | Liver Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D004317 | Doxorubicin |
| ID | Term |
|---|---|
| D003630 | Daunorubicin |
| D018943 | Anthracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
Not provided
Not provided
| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|
| Black |
|
| Asian |
|
| Other |
|
| Hispanic or Latino |
|
| Native Hawaiian or Other Pacific Islander |
|
| North African |
|
| American Indian or Alaska Native |
|
| Unknown |
|
| Europe |
|
| Middle East |
|
| Active Alcohol Consumption |
|
| Child Pugh B |
|
| Child Pugh C |
|
| Loco-regional Treatment |
|
| Radiotherapy |
|
| Sorafenib |
|
| Other Systemic Anticancer Therapy |
|
| Type 2 Diabetes Mellitus |
|
| Diabetes Mellitus |
|
| Hypercholestrolaemia |
|
| Varices Oesophageal |
|
| Chronic Obstructive Pulmonary Disease |
|
| Thrombocytopenia |
|
| No |
|
| Unknown |
|
| No |
|
| Macroscopic Portal Vein or Portal Branch Vascular Invasion - No |
|
| Supra-hepatic Vascular Invasion Vein - Yes |
|
| Supra-hepatic Vascular Invasion Vein - No |
|
| Vascular Invasion (Portal and/or Supra Hepatic) - Yes |
|
| Vascular Invasion (Portal and/or Supra Hepatic) - No |
|
| No |
|
| Unknown |
|
| No |
|
| Unknown |
|
| Hepatitis C Virus |
|
| Nonalcoholic Steatohepatitis |
|
| Unknown |
|
| Hepatitis B Virus |
|
| Other |
|
| Hemochromatosis |
|
| Autoimmune |
|
| Primary Biliary Cirrhosis |
|
| Multiple Nodules |
|
| Infiltrate HCC |
|
| Unknown |
|
| OS up to 45 Months |
|
The hazard ratio was controlled for the overall type I error rate at 5% (2-sided) corresponding to 95% confidence interval (CI) and type II error rate as 15%. |
| Superiority |
| Follow-up 45 month assessment: the primary aim was to demonstrate the superiority of DT pooled (20 mg/m2 and 30 mg/m2) compared to BSC treatment and not individual DT groups per protocol. OS was estimated using the Kaplan-Meier method. The comparison of treatment groups (pooled DT groups versus BSC group) was performed using a non-stratified log-rank test as the primary analysis. The Cox model and Wilcoxon test was used for sensitivity analysis. | Log Rank | Log rank test is used after checking the proportional hazards (PH) assumption is valid. The Wilcoxon test is used when the PH assumption fails. | 0.796 | Treatment comparison of DT pooled with BCS used non-stratified Log-rank test at significance level p=0.05. | Hazard Ratio (HR) | 1.00 | 2-Sided | 95 | The hazard ratio was controlled for the overall type I error rate at 5% (2-sided) corresponding to 95% confidence interval (CI) and type II error rate as 15%. | Superiority |
| OG002 | Doxorubicin Transdrug Pooled | The DT 20 mg/m2 and 30 mg/m2 treatment group were pooled together for PFS comparison to BCS. |
| OG003 | Best Standard of Care | Patients randomized in the control group received treatment according to the investigator's choice, until disease progression or unacceptable toxicity. |
|
|
|
| OG001 |
| Doxorubicin Transdrug at 30 mg/m2 |
DT will be infused over 6 hours through the IV route at dose of 30 mg/m2 on Day 1 and will be repeated every 4 weeks until disease progression or unacceptable toxicity Doxorubicin |
| OG002 | Doxorubicin Transdrug Pooled | The DT 20 mg/m2 and 30 mg/m2 treatment group were pooled together for ORR comparison to BCS. |
| OG003 | Best Standard of Care | Patients randomized in the control group will receive treatment according to the investigator's choice, until disease progression or unacceptable toxicity Best Standard of Care |
|
|
|
Patients randomized in the control group received treatment according to the investigator's choice, until disease progression or unacceptable toxicity.
|
|
| Best Standard of Care (BSC) |
Patients randomized in the control group received treatment according to the investigator's choice, until disease progression or unacceptable toxicity. |
|
|
|
|
| OG002 | Best Standard of Care (BSC) | Patients randomized in the control group received treatment according to the investigator's choice, until disease progression or unacceptable toxicity. |
|
|
Patients randomized in the control group received treatment according to the investigator's choice, until disease progression or unacceptable toxicity.
|
|
| OG002 | Best Standard of Care (BSC) | Patients randomized in the control group received treatment according to the investigator's choice, until disease progression or unacceptable toxicity. |
|
|