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

NCT00508625 | Completed Phase 2

• 1 other identifier: 20050190
• Study Type: interventional
• Target: 213
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Objective response rate (CR and PR) by modified RECIST

  Until disease progression, drug intolerability or withdrawal of consent

Secondary Outcomes (6)

• Progression free survival

  Until disease progression, drug intolerability or withdrawal of consent

• Time to response

  Until disease progression, drug intolerability or withdrawal of consent

• Duration of response

  Until disease progression, drug intolerability or withdrawal of consent

• Time to progression

  Until disease progression, drug intolerability or withdrawal of consent

• Overall response rate (complete, partial or stable response)

  Until disease progression, drug intolerability or withdrawal of consent

Study Arms (5)

C

OTHER

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; Drug: Carboplatin; Drug: Paclitaxel

E

EXPERIMENTAL

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); Drug: Bevacizumab; Drug: Carboplatin; Drug: Paclitaxel

B

EXPERIMENTAL

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); Drug: Carboplatin; Drug: Paclitaxel

A

OTHER

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

Drug: Carboplatin; Drug: Paclitaxel

D

EXPERIMENTAL

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); Drug: Bevacizumab; Drug: Carboplatin; Drug: Paclitaxel

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).

Also known as: Dulanermin

B; D; E

Bevacizumab DRUG

Bevacizumab is a recombinant humanized version of a murine antibody to vascular endothelial growth factor (VEGF).

Also known as: Avastin

C; D; E

Carboplatin DRUG

Standard platinum based chemotherapy

A; B; C; D; E

Paclitaxel DRUG

Standard taxane chemotherapy

A; B; C; D; E

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Amgen: lead
• Genentech, Inc.: collaborator

Related Publications (1)

• Besse B, Planchard D, Veillard AS, Taillade L, Khayat D, Ducourtieux M, Pignon JP, Lumbroso J, Lafontaine C, Mathiot C, Soria JC. Phase 2 study of frontline bortezomib in patients with advanced non-small cell lung cancer. Lung Cancer. 2012 Apr;76(1):78-83. doi: 10.1016/j.lungcan.2011.09.006. Epub 2011 Dec 18.

  PMID: 22186627 DERIVED

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

TNFSF10 protein, human; Bevacizumab; Carboplatin; Paclitaxel

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2007
• First Posted: July 30, 2007
• Study Start: June 1, 2006
• Primary Completion: March 1, 2009
• Study Completion: November 1, 2011
• Last Updated: June 14, 2016

Record last verified: 2016-06