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

Sponsor
Amgen
Study ID
NCT00508625
Phase
PHASE2
Status
Completed

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • AMG 951 (rhApo2L/TRAIL) — DRUG
    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).
  • Bevacizumab — DRUG
    Bevacizumab is a recombinant humanized version of a murine antibody to vascular endothelial growth factor (VEGF).
  • Carboplatin — DRUG
    Standard platinum based chemotherapy
  • Paclitaxel — DRUG
    Standard taxane chemotherapy

Study Details

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.

Key Dates

First listed
Jul 30, 2007
Start date
Jun 30, 2006
Status verified
Jun 2016
Primary completion
Mar 31, 2009
Completion
Nov 30, 2011

Study Design

Enrollment
213 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Other: 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.
  • 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.
  • 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.
  • Other: A
    40 subjects will receive up to 6 cycles of Carboplatin (AUC = 6.0mg/ml.min) and Paclitaxel (200mg/m2) only
  • 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.

Primary Outcome Measure

Objective response rate (CR and PR) by modified RECIST [ Time Frame: Until disease progression, drug intolerability or withdrawal of consent ]

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