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This was an open-label study conducted comparing the toxicity and antitumor activity of ABI-007 (Abraxane®, nab®-paclitaxel) to docetaxel (Taxotere).
This was an open-label, randomized study to compare the following regimens with respect to toxicity and antitumor activity:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ABI-007 300 mg/m^2 q3w | Experimental | ABI-007 300 mg/m^2 administered once every third week (q3w). |
|
| ABI-007 100 mg/m^2 weekly | Experimental | ABI-007 100 mg/m^2 once weekly for 3 weeks followed by 1 week of rest |
|
| ABI-007 150 mg/m^2 weekly | Experimental | ABI-007 150 mg/m^2 once weekly for 3 weeks followed by 1 week of rest |
|
| Docetaxel 100 mg/m^2, q3w | Active Comparator | Docetaxel (Taxotere) 100 mg/m^2 administered once every third week (q3w). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ABI-007 | Drug | ABI-007 administered by intravenous infusion over 30 minutes at one of three different dosing levels (100, 150 or 300 mg/m^2) with a treatment cycle length of either 3 or 4 weeks depending upon treatment arm assignment. |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Showing an Overall Response As Assessed by the Independent Radiology Reader and by the Investigator | Percentage of participants who achieve an objective confirmed complete or partial overall response based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0. A complete response (CR) is the disappearance of all known disease and no new sites or disease related symptoms. A partial response (PR) is >= 30% decrease in the sum of the longest diameters of target lesion. PR was also recorded when all measurable disease has completely disappeared, but a non-measurable component (ie, ascites) is still present but not progressing. Overall response (ORR) = CR+PR. | Day 1 up to 95 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Stable Disease for ≥ 16 Weeks, or Complete or Partial Overall Response | Known as the disease control rate, this outcome measures the percentage of participants with stable disease for 16 weeks or more, or had a confirmed complete or partial response (see outcome #1 for confirmed response definitions). Assessments made by independent radiology and by investigators are reported separately |
| Measure | Description | Time Frame |
|---|---|---|
| Nadir of Myelosuppression (Over All Cycles) as Measured by Absolute Neutrophils (ANC), White Blood Cells (WBC) and Platelet Counts | Maximal degree of myelosuppression is represented by the nadir in absolute neutrophil (ANC), white blood cell (WBC), and platelet measurements over all treatment cycles. | Day 1 up to 125 weeks |
Inclusion Criteria:
Patients had to meet the following criteria to be eligible for the study:
Pathologically confirmed adenocarcinoma of the breast.
No prior chemotherapy for metastatic breast cancer.
Stage IV disease.
Measurable disease (must have been ≥ 2.0 cm, except for pulmonary lesions that were well documented on CT scan that were ≥ 1.0 cm).
At least 3 weeks since prior cytotoxic chemotherapy (patients should have recovered from all acute effects of such therapy.
At least 4 weeks since radiotherapy, with full recovery. The measurable disease was completely outside the radiation portal or there was radiologic or clinical exam proof of progressive disease within the radiation portal.
At least 4 weeks since major surgery, with full recovery.
Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
Age ≥18 years.
Patient had the following blood counts at Baseline:
Patient had the following baseline blood chemistry levels:
Peripheral neuropathy Grade 0 or 1 by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE).
If female of childbearing potential, pregnancy test was negative (within 72 hours of the first dose of study drug).
If fertile, the patient agreed to use an effective method to avoid pregnancy for the duration of the study.
Informed consent had been obtained.
Exclusion Criteria:
Patients who met any of the following criteria were excluded from the study:
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| Name | Affiliation | Role |
|---|---|---|
| Jose Iglesias, MD | Abraxis BioScience, LLC, a wholly owned subsidiary of Celgene Corporation | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Study Sites in Russia and the Ukraine | Kiev | 01021 | Ukraine |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23563958 | Background | O'Shaughnessy J, Gradishar WJ, Bhar P, Iglesias J. Nab-paclitaxel for first-line treatment of patients with metastatic breast cancer and poor prognostic factors: a retrospective analysis. Breast Cancer Res Treat. 2013 Apr;138(3):829-37. doi: 10.1007/s10549-013-2447-8. Epub 2013 Apr 6. | |
| 19470941 | Result | Gradishar WJ, Krasnojon D, Cheporov S, Makhson AN, Manikhas GM, Clawson A, Bhar P. Significantly longer progression-free survival with nab-paclitaxel compared with docetaxel as first-line therapy for metastatic breast cancer. J Clin Oncol. 2009 Aug 1;27(22):3611-9. doi: 10.1200/JCO.2008.18.5397. Epub 2009 May 26. |
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Three hundred and two patients were enrolled and randomized between November 2005 and June 2006, of which 300 received study drug and were evaluated for response and safety. Data below represents data cut-off 31 March 2008.
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| ID | Title | Description |
|---|---|---|
| FG000 | ABI-007 300 mg/m^2 q3w | ABI-007 300 mg/m^2 administered once every third week (q3w). |
| FG001 | ABI-007 100 mg/m^2 Weekly | ABI-007 100 mg/m^2 once weekly for 3 weeks followed by 1 week of rest |
| FG002 | ABI-007 150 mg/m^2 Weekly | ABI-007 150 mg/m^2 once weekly for 3 weeks followed by 1 week of rest |
| FG003 | Docetaxel 100 mg/m^2 q3w | Docetaxel (Taxotere) 100 mg/m^2 administered once every third week (q3w). |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | ABI-007 300 mg/m^2 q3w | ABI-007 300 mg/m^2 administered once every third week (q3w). |
| BG001 | ABI-007 100 mg/m^2 Weekly | ABI-007 100 mg/m^2 once weekly for 3 weeks followed by 1 week of rest |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage of Participants Showing an Overall Response As Assessed by the Independent Radiology Reader and by the Investigator | Percentage of participants who achieve an objective confirmed complete or partial overall response based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0. A complete response (CR) is the disappearance of all known disease and no new sites or disease related symptoms. A partial response (PR) is >= 30% decrease in the sum of the longest diameters of target lesion. PR was also recorded when all measurable disease has completely disappeared, but a non-measurable component (ie, ascites) is still present but not progressing. Overall response (ORR) = CR+PR. | The treated population consisted of all randomized participants who received at least one dose of study drug | Posted | Nov 2010 | Number | 95% Confidence Interval | percentage of participants | Day 1 up to 95 weeks |
|
Day 1 up to 125 weeks
Treatment-emergent AEs defined as AEs that begin or worsen in grade after the first dose of study drug through 30 days after the last dose of study drug.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | ABI-007 300 mg/m^2 q3w | ABI-007 300 mg/m^2 administered once every third week (q3w). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutropenia | Blood and lymphatic system disorders | MedDRA (6.1) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA (6.1) | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Associate Director, Clinical Trials Disclosure | Celgene Corporation | 1-888-260-1599 | clinicaltrialdisclosure@celgene.com |
Not provided
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000068196 | Albumin-Bound Paclitaxel |
| D000077143 | Docetaxel |
| ID | Term |
|---|---|
| D017239 | Paclitaxel |
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 |
Not provided
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|
| Docetaxel | Drug | Docetaxel dosed q3w at 100 mg/m^2 |
|
|
| Day 1 up to 95 weeks |
| Kaplan-Meier Estimates for Progression-free Survival (PFS) | PFS was defined as the time from the date of randomization to the start of disease progression (PD) or patient death (any cause), whichever occurred first. Patients without disease progression were censored at the last time the patient was known to be progression-free. Patients who initiated new anticancer therapy prior to documented progression or death were censored at the start of new therapy. Disease progression was assessed separately by investigators and by an independent radiologist. Both assessments are offered. Response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 (Therasse, 2000). PD for target lesions is defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum of the longest diameters recorded since the treatment started; or the appearance of one or more new lesions; or the unequivocal progression of a non-target lesion. | Day 1 up to 95 weeks |
| Kaplan-Meier Estimates for Duration of Response Based on Independent Radiology Assessment of Response and Progression | Duration of response was measured as the progression-free survival on patients with confirmed response. The independent radiology assessment is offered here. Response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 (Therasse, 2000) and is defined in outcome #1. Progression-free survival is defined in outcome #3. | Day 1 - 95 weeks |
| Kaplan-Meier Estimates for Duration of Response Based on Investigator Assessment of Response and Progression | Duration of response was measured as the progression-free survival on patients with confirmed response. The investigator assessment is offered here. Response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 (Therasse, 2000) and is defined in outcome #1. Progression-free survival is defined in outcome #3. | Day 1 - 95 weeks |
| Kaplan-Meier Estimate for Overall Survival (OS) | Participant survival was defined as the date of randomization to the date of death. Participants that were alive at the time of analysis were censored at the last known time that the participant was alive. The final analysis of mature overall survival was conducted after 2 years of follow-up (data cutoff date 31 Jan 2010). | Day 1 to 221 weeks |
| Participants With Treatment-Emergent, Treatment-Related Adverse Events | Summary of participants who had treatment-emergent that were treatment-related in the opinion of the investigator, and summarized in a variety of categories. The National Cancer Institute (NCI)'s Common Terminology Criteria for AEs (CTCAE) was used to grade AE severity: severity grade 3= severe and undesirable AE. Severity grade 4= life-threatening or disabling AE. Severity grade 5 = death. | Day 1 up to 125 weeks |
| Nadir of Myelosuppression (Over All Cycles) as Measured by Hemoglobin (Hb) Counts |
Maximal degree of myelosuppression is represented by the nadir in hemoglobin (Hb) measurements over all treatment cycles. |
| Day 1 up to 125 weeks |
| 22728026 | Result | Gradishar WJ, Krasnojon D, Cheporov S, Makhson AN, Manikhas GM, Clawson A, Bhar P, McGuire JR, Iglesias J. Phase II trial of nab-paclitaxel compared with docetaxel as first-line chemotherapy in patients with metastatic breast cancer: final analysis of overall survival. Clin Breast Cancer. 2012 Oct;12(5):313-21. doi: 10.1016/j.clbc.2012.05.001. Epub 2012 Jun 23. |
| Unacceptable toxicity |
|
| Adverse Event |
|
| Physician Decision |
|
| Lost to Follow-up |
|
| Withdrawal by Subject |
|
| BG002 | ABI-007 150 mg/m^2 | ABI-007 150 mg/m^2 once weekly for 3 weeks followed by 1 week of rest. |
| BG003 | Docetaxel 100 mg/m^2 q3w | Docetaxel (Taxotere) 100 mg/m^2 administered once every third week (q3w). |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Age, Customized | Number | Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | Participants |
|
| Weight | Mean | Standard Deviation | Kg |
|
| Eastern Cooperative Oncology Group (ECOG) Performance Status | A scale used to assess the progress of disease in a patient, how the disease affects the daily living abilities of the patient, and determine appropriate treatment and prognosis. | Number | participants |
|
| Menopausal Status | Number | Participants |
|
| Physician Assessment of Sensory Neuropathy | The physician assessed sensory neuropathy using the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) of "Neurology -- Neuropathy - Sensory". The scale is 0=normal and 1=asymptomatic; loss of deep tendon reflexes or paresthesia (including tingling) but not interfering with function. | Number | Participants |
|
| Time from Primary Diagnosis and from First Metastasis/Relapse to Study Entry | Median | Full Range | Years |
|
| Current Site of Metastasis/Relapse | Patients may have multiple sites of metastasis/relapse. | Number | Participants |
|
| Dominant Current Site of Metastasis/Relapse | Number | Participants |
|
| Stage at Primary Diagnosis | Invasive breast cancer stages:
| Number | participants |
|
| Number of Lesions (Target + Non-Target) | Target lesions were selected on the basis of their size (those with the longest diameter) and their suitability for accurate repeat measurements (either by imaging techniques or clinically). | Number | Participants |
|
ABI-007 300 mg/m^2 administered once every third week (q3w). |
| OG001 | ABI-007 100 mg/m^2 Weekly | ABI-007 100 mg/m^2 once weekly for 3 weeks followed by 1 week of rest |
| OG002 | ABI-007 150 mg/m^2 Weekly | ABI-007 150 mg/m^2 once weekly for 3 weeks followed by 1 week of rest |
| OG003 | Docetaxel 100 mg/m^2 q3w | Docetaxel (Taxotere) 100 mg/m^2 administered once every third week (q3w). |
|
|
|
| Secondary | Percentage of Participants With Stable Disease for ≥ 16 Weeks, or Complete or Partial Overall Response | Known as the disease control rate, this outcome measures the percentage of participants with stable disease for 16 weeks or more, or had a confirmed complete or partial response (see outcome #1 for confirmed response definitions). Assessments made by independent radiology and by investigators are reported separately | The treated population consisted of all randomized participants who received at least one dose of study drug | Posted | Nov 2010 | Number | 95% Confidence Interval | percentage of participants | Day 1 up to 95 weeks |
|
|
|
|
| Secondary | Kaplan-Meier Estimates for Progression-free Survival (PFS) | PFS was defined as the time from the date of randomization to the start of disease progression (PD) or patient death (any cause), whichever occurred first. Patients without disease progression were censored at the last time the patient was known to be progression-free. Patients who initiated new anticancer therapy prior to documented progression or death were censored at the start of new therapy. Disease progression was assessed separately by investigators and by an independent radiologist. Both assessments are offered. Response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 (Therasse, 2000). PD for target lesions is defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum of the longest diameters recorded since the treatment started; or the appearance of one or more new lesions; or the unequivocal progression of a non-target lesion. | The treated population consisted of all randomized participants who received at least one dose of study drug | Posted | Nov 2010 | Median | 95% Confidence Interval | months | Day 1 up to 95 weeks |
|
|
|
|
| Secondary | Kaplan-Meier Estimates for Duration of Response Based on Independent Radiology Assessment of Response and Progression | Duration of response was measured as the progression-free survival on patients with confirmed response. The independent radiology assessment is offered here. Response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 (Therasse, 2000) and is defined in outcome #1. Progression-free survival is defined in outcome #3. | Patients with a confirmed CR or PR were included in this analysis. Patients who did not progress or die were censored at the last known time when patient was progression free. Patients who initiated other anticancer therapy prior to progression were censored at the time when new anticancer therapy was initiated. | Posted | Nov 2010 | Median | 95% Confidence Interval | months | Day 1 - 95 weeks |
|
|
|
|
| Secondary | Kaplan-Meier Estimates for Duration of Response Based on Investigator Assessment of Response and Progression | Duration of response was measured as the progression-free survival on patients with confirmed response. The investigator assessment is offered here. Response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 (Therasse, 2000) and is defined in outcome #1. Progression-free survival is defined in outcome #3. | Patients with a confirmed CR or PR were included in this analysis. Patients who did not progress or die were censored at the last known time when patient was progression free. Patients who initiated other anticancer therapy prior to progression were censored at the time when new anticancer therapy was initiated. | Posted | Median | 95% Confidence Interval | months | Day 1 - 95 weeks |
|
|
|
|
| Secondary | Kaplan-Meier Estimate for Overall Survival (OS) | Participant survival was defined as the date of randomization to the date of death. Participants that were alive at the time of analysis were censored at the last known time that the participant was alive. The final analysis of mature overall survival was conducted after 2 years of follow-up (data cutoff date 31 Jan 2010). | The treated population consisted of all randomized participants who received at least one dose of study drug | Posted | Median | 95% Confidence Interval | months | Day 1 to 221 weeks |
|
|
|
|
| Other Pre-specified | Nadir of Myelosuppression (Over All Cycles) as Measured by Absolute Neutrophils (ANC), White Blood Cells (WBC) and Platelet Counts | Maximal degree of myelosuppression is represented by the nadir in absolute neutrophil (ANC), white blood cell (WBC), and platelet measurements over all treatment cycles. | The treated population consisted of all randomized participants who received at least one dose of study drug, and had blood tests performed following treatment. Three participants dropped out after a single dose so have no post-treatment lab values. | Posted | Nov 2010 | Mean | Standard Deviation | 10^9/L | Day 1 up to 125 weeks |
|
|
|
| Secondary | Participants With Treatment-Emergent, Treatment-Related Adverse Events | Summary of participants who had treatment-emergent that were treatment-related in the opinion of the investigator, and summarized in a variety of categories. The National Cancer Institute (NCI)'s Common Terminology Criteria for AEs (CTCAE) was used to grade AE severity: severity grade 3= severe and undesirable AE. Severity grade 4= life-threatening or disabling AE. Severity grade 5 = death. | The treated population consisted of all randomized participants who received at least one dose of study drug | Posted | Nov 2010 | Number | participants | Day 1 up to 125 weeks |
|
|
|
| Other Pre-specified | Nadir of Myelosuppression (Over All Cycles) as Measured by Hemoglobin (Hb) Counts | Maximal degree of myelosuppression is represented by the nadir in hemoglobin (Hb) measurements over all treatment cycles. | The treated population consisted of all randomized participants who received at least one dose of study drug, and had blood tests performed following treatment. Three participants dropped out after a single dose so have no post-treatment lab values. | Posted | Nov 2010 | Mean | Standard Deviation | g/L | Day 1 up to 125 weeks |
|
|
|
| 14 |
| 76 |
| 75 |
| 76 |
| EG001 | ABI-007 100 mg/m^2 Weekly | ABI-007 100 mg/m^2 once weekly for 3 weeks followed by 1 week of rest | 12 | 76 | 75 | 76 |
| EG002 | ABI-007 150 mg/m^2 Weekly | ABI-007 150 mg/m^2 once weekly for 3 weeks followed by 1 week of rest | 11 | 74 | 73 | 74 |
| EG003 | Docetaxel 100 mg/m^2 q3w | Docetaxel (Taxotere) 100 mg/m^2 administered once every third week (q3w). | 56 | 74 | 73 | 74 |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA (6.1) | Systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA (6.1) | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (6.1) | Systematic Assessment |
|
| Bowel peristalsis increased | Gastrointestinal disorders | MedDRA (6.1) | Systematic Assessment |
|
| Colitis | Gastrointestinal disorders | MedDRA (6.1) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (6.1) | Systematic Assessment |
|
| Gastritis | Gastrointestinal disorders | MedDRA (6.1) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (6.1) | Systematic Assessment |
|
| Erysipelas | Infections and infestations | MedDRA (6.1) | Systematic Assessment |
|
| Chronic sinusitis | Infections and infestations | MedDRA (6.1) | Systematic Assessment |
|
| Cardiopulmonary failure | Cardiac disorders | MedDRA (6.1) | Systematic Assessment |
|
| Body temperature increased | Investigations | MedDRA (6.1) | Systematic Assessment |
|
| Liver function test abnormal | Investigations | MedDRA (6.1) | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA (6.1) | Systematic Assessment |
|
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA (6.1) | Systematic Assessment |
|
| Lymphocele | Vascular disorders | MedDRA (6.1) | Systematic Assessment |
|
| Thrombophlebitis | Vascular disorders | MedDRA (6.1) | Systematic Assessment |
|
| Optic ischaemic neuropathy | Eye disorders | MedDRA (6.1) | Systematic Assessment |
|
| Inflammation localised | General disorders | MedDRA (6.1) | Systematic Assessment |
|
| Jaundice | Hepatobiliary disorders | MedDRA (6.1) | Systematic Assessment |
|
| Hypersensitivity | Immune system disorders | MedDRA (6.1) | Systematic Assessment |
|
| Convulsion | Nervous system disorders | MedDRA (6.1) | Systematic Assessment |
|
| Urinary retention | Renal and urinary disorders | MedDRA (6.1) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (6.1) | Systematic Assessment |
|
| Neuropathy | Nervous system disorders | MedDRA (6.1) | Systematic Assessment |
|
| Neuropathy peripheral | Nervous system disorders | MedDRA (6.1) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (6.1) | Systematic Assessment |
|
| Hypoaesthesia | Nervous system disorders | MedDRA (6.1) | Systematic Assessment |
|
| Peripheral motor neuropathy | Nervous system disorders | MedDRA (6.1) | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA (6.1) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (6.1) | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA (6.1) | Systematic Assessment |
|
| Nail disorder | Skin and subcutaneous tissue disorders | MedDRA (6.1) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (6.1) | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (6.1) | Systematic Assessment |
|
| Skin hyperpigmentation | Skin and subcutaneous tissue disorders | MedDRA (6.1) | Systematic Assessment |
|
| Skin toxicity | Skin and subcutaneous tissue disorders | MedDRA (6.1) | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA (6.1) | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA (6.1) | Systematic Assessment |
|
| Performance status decreased | General disorders | MedDRA (6.1) | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA (6.1) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (6.1) | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA (6.1) | Systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | MedDRA (6.1) | Systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA (6.1) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (6.1) | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (6.1) | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (6.1) | Systematic Assessment |
|
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA (6.1) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (6.1) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (6.1) | Systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA (6.1) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (6.1) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (6.1) | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (6.1) | Systematic Assessment |
|
| Respiratory tract infection viral | Infections and infestations | MedDRA (6.1) | Systematic Assessment |
|
| Respiratory tract infection | Infections and infestations | MedDRA (6.1) | Systematic Assessment |
|
| Gamma glutamyl transferase increased | Investigations | MedDRA (6.1) | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA (6.1) | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA (6.1) | Systematic Assessment |
|
| Body temperature increased | Investigations | MedDRA (6.1) | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (6.1) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (6.1) | Systematic Assessment |
|
| Hyperaemia | Vascular disorders | MedDRA (6.1) | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA (6.1) | Systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | MedDRA (6.1) | Systematic Assessment |
|
Publications of this multicenter trial should include input from INVESTIGATORS, his/her colleagues, and SPONSOR personnel. Such input should be reflected in publication authorship, and agreement regarding order of authors should be established before writing a manuscript. Subsequent to the multicenter publication or one year after completion of the study, whichever occurs first, an investigator and/or his/her colleagues may publish the results of INVESTIGATOR's part of the study independently.
| D017437 |
| Skin and Connective Tissue Diseases |
| Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D000418 | Albumins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| Investigator Assessed Disease Control |
|
| Cochran-Mantel-Haenszel |
CMH test was stratified by study site. |
| 0.009 |
| Superiority or Other (legacy) |
| Independent assessed DCR | Cochran-Mantel-Haenszel | CMH test was stratified by study site. | 0.017 | Superiority or Other (legacy) |
| Independent assessed DCR | Cochran-Mantel-Haenszel | CMH test was stratified by study site. | >0.05 | Superiority or Other (legacy) |
| Independent assessed DCR | Cochran-Mantel-Haenszel | CMH test was stratified by study site. | >0.05 | Superiority or Other (legacy) |
| Independent assessed DCR | Cochran-Mantel-Haenszel | CMH test was stratified by study site. | >0.05 | Superiority or Other (legacy) |
| Independent assessed DCR | Cochran-Mantel-Haenszel | CMH test was stratified by study site. | 0.085 | Superiority or Other (legacy) |
| Investigator assessed disease control rate (DCR), ie, SD >= 16 weeks, or CR or PR | Cochran-Mantel-Haenszel | CMH test was stratified by study site. | 0.007 | A step-down approach was used to compare treatment regimens. First an overall "test of treatment difference" (a 3-degree-of -freedom test) was performed. Pairwise comparison was performed only if this test was significant. | Superiority or Other (legacy) |
| Investigator assessed DCR | Cochran-Mantel-Haenszel | CMH test was stratified by study site. | >0.05 | 95 | Superiority or Other (legacy) |
| Investigator assessed DCR | Cochran-Mantel-Haenszel | CMH test was stratified by study site. | 0.009 | Superiority or Other (legacy) |
| Investigator assessed DCR | Cochran-Mantel-Haenszel | CMH test was stratified by study site. | 0.005 | 2-Sided | Superiority or Other (legacy) |
| Investigator assessed DCR | Cochran-Mantel-Haenszel | CMH test was stratified by study site. | >0.05 | Superiority or Other (legacy) |
| Investigator assessed DCR | Cochran-Mantel-Haenszel | CMH test was stratified by study site. | 0.098 | 95 | Superiority or Other (legacy) |
| Investigator assessed DCR | Cochran-Mantel-Haenszel | CMH test was stratified by study site. | 0.014 | 95 | Superiority or Other (legacy) |
| Investigator Assessment for PFS |
|
Independent assessment |
| Log Rank |
| 0.0524 |
| Hazard Ratio (HR) |
| 0.607 |
| Superiority or Other (legacy) |
| Independent assessment | Log Rank | 0.0065 | Hazard Ratio (HR) | 0.495 | Superiority or Other (legacy) |
| Independent assessment | Log Rank | >0.05 | Superiority or Other (legacy) |
| Independent assessment | Log Rank | >0.05 | Superiority or Other (legacy) |
| Independent assessment | Log Rank | >0.05 | Superiority or Other (legacy) |
| Independent assessment | Log Rank | >0.05 | Superiority or Other (legacy) |
| Investigator assessment | Log Rank | 0.008 | A step-down approach was used to compare treatment regimens. First an overall "test of treatment difference" (a 3-degree-of -freedom test) was performed. Pairwise comparisons was performed only if this test was significant. | Superiority or Other (legacy) |
| Investigator assessment | Log Rank | >0.05 | Superiority or Other (legacy) |
| Investigator assessment | Log Rank | >0.05 | Superiority or Other (legacy) |
| Investigator assessment | Log Rank | 0.012 | Hazard Ratio (HR) | 0.568 | Superiority or Other (legacy) |
| Investigator assessment | Log Rank | 0.001 | Hazard Ratio (HR) | 1.972 | Superiority or Other (legacy) |
| Investigator assessment | Log Rank | 0.076 | Hazard Ratio (HR) | 0.702 | Superiority or Other (legacy) |
| Investigator assessment | Log Rank | >0.05 | Superiority or Other (legacy) |
Investigator assessment |
| Log Rank |
| 0.022 |
| Superiority or Other (legacy) |
| Investigator assessment | Log Rank | >0.05 | Superiority or Other (legacy) |
| Investigator assessment | Log Rank | >0.05 | Superiority or Other (legacy) |
| Investigator assessment | Log Rank | 0.005 | Superiority or Other (legacy) |
| Investigator assessment | Log Rank | >0.05 | Superiority or Other (legacy) |
| Investigator assessment | Log Rank | >0.05 | Superiority or Other (legacy) |
| Log Rank |
| >0.05 |
| 95 |
| Superiority or Other (legacy) |
| Log Rank | >0.05 | 95 | Superiority or Other (legacy) |
| Log Rank | >0.05 | 95 | Superiority or Other (legacy) |
| Log Rank | 0.069 | Hazard Ratio (HR) | 0.686 | 95 | Superiority or Other (legacy) |
| Log Rank | >0.05 | 95 | Superiority or Other (legacy) |
| Log Rank | 0.008 | Hazard Ratio (HR) | 1.740 | 95 | Superiority or Other (legacy) |
| WBC |
|
| Platelet |
|
| >=1 treatment-related AE |
|
| >=1 serious AE |
|
| >=1 treatment-related serious AE |
|
| >=1 severe (grade 3-5) treatment-related AE |
|
| Grade 3-5 Neutropenia |
|
| Grade 3-5 Febrile neutropenia |
|
| Grade 3-5 Sensory neuropathy |
|
| >=1 AE with outcome of death |
|
| >=1 treatment-related AE with outcome of death |
|
| >=1 treatment-related AE drug discontinued |
|
| >=1 treatment-related AE drug dosage reduced |
|
| >=1 treatment-related AE drug interrupted |
|