A Study of AMG 951 [rhApo2L/TRAIL] in Subjects With Previously Untreated Non-Small Cell Lung Cancer (NSCLC) Treated With Chemotherapy +/- Bevacizumab

This study has been completed.
Sponsor:
Collaborator:
Genentech
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT00508625
First received: July 26, 2007
Last updated: October 29, 2012
Last verified: October 2012
  Purpose

This is a phase 2 multicenter, open label, randomized study of AMG 951 (rhApo2L/TRAIL) in subjects with previously untreated stage IIIb/IV NSCLC treated with chemotherapy with or without bevacizumab.

Subjects will be assigned to a set of treatment groups depending on their eligibility to receive bevacizumab. Subjects with squamous NSCLC and/or CNS metastases will not be eligible to receive bevacizumab and will be assigned to either cohort A or B (provided all other eligibility criteria are met). Subjects who are eligible to receive bevacizumab will be assigned to cohort C, D or E. Cohorts are defined as follows:

Subjects with squamous NSCLC or CNS mets:

Cohort A: Chemotherapy alone Cohort B: Chemotherapy plus 8 mg/kg AMG 951 for 5 days

Subjects without squamous NSCLC and without CNS mets:

Cohort C: Chemotherapy and bevacizumab Cohort D: Chemotherapy, bevacizumab plus 8 mg/kg AMG 951 for 5 days Cohort E: Chemotherapy, bevacizumab plus up to 20 mg/kg AMG 951 for 2 days Approximately forty subjects will be recruited to each cohort.


Condition Intervention Phase
Non-Small Cell Lung Cancer
Drug: AMG 951 (rhApo2L/TRAIL)
Drug: Bevacizumab
Drug: Carboplatin
Drug: Paclitaxel
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter, Open Label, Randomized Study of AMG 951 in Subjects With Previously Untreated Stage IIIb/IV Non-Small Cell Lung Cancer (NSCLC) Treated With Chemotherapy With or Without Bevacizumab

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Objective response rate (CR and PR) by modified RECIST [ Time Frame: Until disease progression, drug intolerability or withdrawal of consent ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression free survival [ Time Frame: Until disease progression, drug intolerability or withdrawal of consent ] [ Designated as safety issue: No ]
  • Time to response [ Time Frame: Until disease progression, drug intolerability or withdrawal of consent ] [ Designated as safety issue: No ]
  • Duration of response [ Time Frame: Until disease progression, drug intolerability or withdrawal of consent ] [ Designated as safety issue: No ]
  • Time to progression [ Time Frame: Until disease progression, drug intolerability or withdrawal of consent ] [ Designated as safety issue: No ]
  • Overall response rate (complete, partial or stable response) [ Time Frame: Until disease progression, drug intolerability or withdrawal of consent ] [ Designated as safety issue: No ]
  • Overall Survival [ Time Frame: Until disease progression, drug intolerability or withdrawal of consent ] [ Designated as safety issue: No ]

Enrollment: 213
Study Start Date: November 2007
Study Completion Date: February 2012
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
C
40 subjects will receive up to 6 cycles of carboplatin (AUC=6.0mg/ml.min) and paclitaxel (200mg/m2) on day 1 of each 21 day cycle plus Bevacizumab (15mg/kg) on day 1 of each 21 day cycle until disease progression, study drug intolerability or withdrawal of consent.
Drug: Bevacizumab
Bevacizumab is a recombinant humanized version of a murine antibody to vascular endothelial growth factor (VEGF). It is given at a dose of 15mg/kg on day 1 of a 21 day cycle until disease progression, drug intolerability, withdrawal of consent or end of study.
Other Name: Avastin
Drug: Carboplatin
Standard chemotherapy given at a dose of AUC=6.0mg/ml.min on day 1 of a 21 day cycle for up to a maximum of 6 cycles
Drug: Paclitaxel
Standard chemotherapy given at a dose of 200mg/m2 on day 1 of a 21 day cycle for up to a maximum of 6 cycles.
Experimental: E
40 subjects will receive up to 6 cycles of carboplatin (AUC=6.0mg/ml.min) and paclitaxel (200mg/m2) on day 1 of each 21 day cycle plus Bevacizumab (15mg/kg) on day 1 and AMG 951 (rhApo2L/TRAIL) (20mg/kg) on days 1-2 per 21 day cycle until disease progression, study drug intolerability or withdrawal of consent.
Drug: AMG 951 (rhApo2L/TRAIL)
AMG 951 is recombinant human Apo2Ligand/Tumor necrosis factor related apoptosis inducing ligand (rhApo2L/TRAIL) that triggers apoptosis through activation of death receptor 4 (DR4) and death receptor 5 (DR5). It is given at a dose of either 8mg/kg for 5 days or 20mg/kg for 2 days per 21 day cycle until disease progression, drug intolerability, withdrawal of consent, or end of study.
Drug: Bevacizumab
Bevacizumab is a recombinant humanized version of a murine antibody to vascular endothelial growth factor (VEGF). It is given at a dose of 15mg/kg on day 1 of a 21 day cycle until disease progression, drug intolerability, withdrawal of consent or end of study.
Other Name: Avastin
Drug: Carboplatin
Standard chemotherapy given at a dose of AUC=6.0mg/ml.min on day 1 of a 21 day cycle for up to a maximum of 6 cycles
Drug: Paclitaxel
Standard chemotherapy given at a dose of 200mg/m2 on day 1 of a 21 day cycle for up to a maximum of 6 cycles.
Experimental: B
40 subjects will receive up to 6 cycles of carboplatin (AUC=6.0mg/ml.min) and paclitaxel (200mg/m2) on day 1 of each 21 day cycle plus AMG 951 (rhApo2L/TRAIL) (8mg/kg) for 5 days per 21 days cycle until disease progression, study drug intolerability or withdrawal of consent.
Drug: AMG 951 (rhApo2L/TRAIL)
AMG 951 is recombinant human Apo2Ligand/Tumor necrosis factor related apoptosis inducing ligand (rhApo2L/TRAIL) that triggers apoptosis through activation of death receptor 4 (DR4) and death receptor 5 (DR5). It is given at a dose of either 8mg/kg for 5 days or 20mg/kg for 2 days per 21 day cycle until disease progression, drug intolerability, withdrawal of consent, or end of study.
Drug: Carboplatin
Standard chemotherapy given at a dose of AUC=6.0mg/ml.min on day 1 of a 21 day cycle for up to a maximum of 6 cycles
Drug: Paclitaxel
Standard chemotherapy given at a dose of 200mg/m2 on day 1 of a 21 day cycle for up to a maximum of 6 cycles.
A
40 subjects will receive up to 6 cycles of Carboplatin (AUC = 6.0mg/ml.min) and Paclitaxel (200mg/m2) only
Drug: Carboplatin
Standard chemotherapy given at a dose of AUC=6.0mg/ml.min on day 1 of a 21 day cycle for up to a maximum of 6 cycles
Drug: Paclitaxel
Standard chemotherapy given at a dose of 200mg/m2 on day 1 of a 21 day cycle for up to a maximum of 6 cycles.
Experimental: D
40 subjects will receive up to 6 cycles of carboplatin (AUC=6.0mg/ml.min) and paclitaxel (200mg/m2) on day 1 of each 21 day cycle plus Bevacizumab (15mg/kg) on day 1 and AMG 951 (rhApo2L/TRAIL) (8mg/kg) on days 1-5 per 21 day cycle until disease progression, study drug intolerability or withdrawal of consent.
Drug: AMG 951 (rhApo2L/TRAIL)
AMG 951 is recombinant human Apo2Ligand/Tumor necrosis factor related apoptosis inducing ligand (rhApo2L/TRAIL) that triggers apoptosis through activation of death receptor 4 (DR4) and death receptor 5 (DR5). It is given at a dose of either 8mg/kg for 5 days or 20mg/kg for 2 days per 21 day cycle until disease progression, drug intolerability, withdrawal of consent, or end of study.
Drug: Bevacizumab
Bevacizumab is a recombinant humanized version of a murine antibody to vascular endothelial growth factor (VEGF). It is given at a dose of 15mg/kg on day 1 of a 21 day cycle until disease progression, drug intolerability, withdrawal of consent or end of study.
Other Name: Avastin
Drug: Carboplatin
Standard chemotherapy given at a dose of AUC=6.0mg/ml.min on day 1 of a 21 day cycle for up to a maximum of 6 cycles
Drug: Paclitaxel
Standard chemotherapy given at a dose of 200mg/m2 on day 1 of a 21 day cycle for up to a maximum of 6 cycles.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed Non-Small Cell Lung Cancer (NSCLC). Mixed tumors will be categorized by the predominant cell type unless small cell elements are present in which case the patient is ineligible. Cytologic or histologic elements can be established on metastatic tumor aspirates or biopsy.
  • Subjects must have advanced NSCLC defined as stage IIIb with malignant pleural effusion or Stage IV or recurrent disease. Subjects with unmeasurable but evaluable disease can be included in the phase 1b study, but disease must be measurable to be included in the phase 2 study
  • Planning to receive up to 6 cycles of chemotherapy
  • ECOG performance status of 0 or 1
  • Life expectancy greater than 3 months
  • ≥18 years old
  • Subjects must sign and date a written Independent Ethics Committee (IEC)-approved Informed Consent Form
  • INR ≤ 1.2 and PTT ≤ ULN within 1 week prior to enrollment

Exclusion Criteria:

Disease Related

  • Prior malignancy other than NSCLC (except in situ basal cell carcinoma or in situ cervical cancer), unless have been treated with curative intent with no evidence of disease for > 3 years
  • Untreated or unstable central nervous system (CNS) metastases. Subjects with treated and stably controlled CNS metastases are eligible for cohorts A and B of the phase 2 part of the study if definitive therapy has been administered (surgery and/or radiation therapy), there is no planned treatment for brain metastases, and the subject is clinically stable and is off corticosteroids or on a stable dose of corticosteroids for at least 2 weeks prior to enrollment
  • Myocardial infarction, or unstable or uncontrolled disease or condition related to or impacting cardiac function (e.g., unstable angina, congestive heart failure [New York Heart Association > class II]) within 1 year of enrollment
  • Uncontrolled hypertension defined as: systolic blood pressure > 150 mm Hg OR diastolic blood pressure > 100 mm Hg (antihypertensive therapy to achieve these parameters is allowable)
  • History of arterial thrombosis, pulmonary embolus, deep vein thrombosis or hemorrhagic disorders within 1 year of enrollment
  • Recent major surgical procedure within 28 days of enrollment
  • Subjects must not have serious non-healing wound ulcer, or bone fracture within 21 days prior to enrollment
  • Persistent history of gross hemoptysis (defined as bright red blood of a ½ teaspoon or more) related to subject's NSCLC
  • Known (documented in medical notes) HIV infection
  • Active infection on day of enrollment
  • Known to be hepatitis C positive OR hepatitis B surface antigen positive
  • Subjects with Gilbert's syndrome

Laboratory

  • Absolute neutrophil count (ANC) < 1.5 x 10*9 /L (without granulocyte-colony stimulating factor support within 2 weeks of enrollment)
  • Platelet count < 100 x 10*9 /L (without transfusion within 2 weeks of enrollment)
  • Hemoglobin < 9 g/dL (subjects may be transfused or receive erythropoietic treatment to meet criterion)
  • Urine protein quantitative value of > 1+ on dipstick or > 30 mg/dL in urinalysis. If quantitative protein is < 500 mg in 24-hour urine collection then subject can be included
  • Significant liver dysfunction as defined by aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 x upper limits of normal (ULN)
  • Alkaline phosphatase > 2.5 x ULN, or alkaline phosphatase > 5 x ULN in the presence of bone or liver metastasis
  • Total bilirubin > 1.5 x ULN
  • Calculated creatinine clearance < 50 mL/min.
  • Hypercalcemia (serum calcium > 12.0 mg/dL or symptomatic)

Medications

  • Prior chemotherapy (except for adjuvant chemotherapy, provided the last dose of adjuvant therapy was received at least one year prior to enrollment), hormonal therapy, radiotherapy (except palliative radiotherapy for bone metastases or radiation therapy for CNS metastases) or immunotherapy for treatment of advanced NSCLC
  • Prior drug treatment or therapy with investigational agents for NSCLC
  • Therapeutic anticoagulation treatment. Prophylactic anticoagulation of venous access devices (eg, with low-dose warfarin [1-2mg/day] or low-dose heparin) is allowed providing INR ≤ 1.2 and PTT is ≤ ULN within 1 week prior to enrollment
  • Chronic daily treatment with aspirin (> 325 mg/day) or non-steroidal anti-inflammatory agents known to inhibit platelet function. Treatment with dipyridamole, ticlopidine, clopidogrel and/or cilostazol is also not allowed.

General Exclusions

  • Participation in clinical trials or undergoing other investigational procedures within 30 days before study enrollment
  • Subject is evidently pregnant (e.g. positive HCG test) or is breast feeding
  • Woman or man with partner of childbearing potential not consenting to use adequate contraceptive precautions i.e. double barrier contraceptive methods (eg diaphragm plus condom), or abstinence during the course of the study and for 6 months after the last study drug administration for women, and 1 month for men.
  • Subject has known sensitivity to any of the products to be administered during the study.
  • Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or comply with study procedures.
  • Any condition which in the investigator's opinion makes the subject unsuitable for study participation
  • Subjects enrolled and dosed in phase 1b will be excluded from phase 2

Exclusion criteria for phase 1b and bevacizumab treatment (cohorts C, D and E) in phase 2

  • Subjects with central nervous system tumor involvement
  • Subjects with squamous NSCLC
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00508625

Sponsors and Collaborators
Amgen
Genentech
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
No publications provided by Amgen

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00508625     History of Changes
Other Study ID Numbers: 20050190
Study First Received: July 26, 2007
Last Updated: October 29, 2012
Health Authority: Belgium: Federal Public Service (FPS) Health, Food Chain Safety and Environment
Czech Republic: State Institute for Drug Control
Finland: Lääkelaitos
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Paul_Ehrlich-Institut Bundesamt fur Sera und Impfstoffe
Hungary: National Institute of Pharmacy
Ireland: Irish Medicines Board
Italy: Local Ethics Committees
Italy: Ministry of Health
Netherlands: CCMO (Centrale Commissie Mensgebonden Onderzoek): Central Committee Human Bound Research
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Slovakia: Ministry of Health
Spain: Agencia Española de Medicamentos y Productos Sanitarios
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Bevacizumab
Carboplatin
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on July 28, 2014