QUILT-2.013: A Trial of AMG 479 or AMG 102 in Combination With Platinum-based Chemotherapy as First-Line Treatment for Extensive Stage Small Cell Lung Cancer

Study Overview
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Brief Summary
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This trial is titled A Phase 1b/2 trial of AMG 479 or AMG 102 with Platinum-Based Chemotherapy as First-Line Treatment for Extensive Stage Small-Cell Lung Cancer (SCLC). Part 1, the phase 1b portion of this study, is a multicenter, open-label investigation to identify safe dose levels of either AMG 102 or AMG 479 in combination with etoposide plus cisplatin or carboplatin in subjects with previously untreated extensive stage SCLC. Part 2, the phase 2 portion of this study, is a multicenter, double-blind, 3-arm investigation to evaluate overall survival of either AMG 102 or AMG 479 in combination with platinum-based chemotherapy.

Official Title
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Amgen Protocol 20060534 - A Phase 1b/2 Trial of AMG 479 or AMG 102 in Combination With Platinum-based Chemotherapy as First-Line Treatment for Extensive Stage Small Cell Lung Cancer

Conditions
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Lung Cancer, Small Cell Lung Cancer, Solid Tumors, Extensive-stage Small Cell Lung Cancer

Intervention / Treatment
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* Drug: AMG 479
* Drug: Etoposide
* Drug: Placebo
* Drug: AMG 102
* Drug: Carboplatin
* Drug: Cisplatin


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria Histologically or cytologically confirmed SCLC Extensive disease, defined by at least one of the following: No limited disease (ie, no disease confined to the ipsilateral hemithorax, which can be safely encompassed within a tolerable radiation field) Extrathoracic metastases Malignant pericardial or pleural effusion Contralateral hilar adenopathy Measurable or nonmeasurable disease, as defined by modified RECIST Eastern Cooperative Oncology Group (ECOG) status 0 or 1 ≥18 years old Life expectancy (with therapy) ≥3 months Adequate hematologic, hepatic, coagulation, renal, and metabolic function Diabetes, if present, must be controlled, with glycosylated hemoglobin (HbA1C) ≤ 8% and fasting glucose levels ≤160 mg/dL Key Exclusion Criteria Prior chemotherapy, chemoradiation, or investigational agent for SCLC Prior radiotherapy to >25% of the bone marrow Symptomatic or untreated central nervous system metastases (with exceptions) Currently or previously treated with biologic, immunologic or other therapies for SCLC Current serious or nonhealing wound or ulcer History of prior concurrent other malignancy (with exceptions) Thorombosis or vascular ischemic events within the last 12 months such as DVT, PE, TIA or MI Any clinically significant medical condition other than cancer (eg, cardiovascular disease or COPD), which could interfere with the safe delivery of study treatment or risk of toxicity

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ARM B<br>Blinded AMG 102 study drug and carboplatin or cisplatin and etoposide | Drug: Etoposide<br>* Etoposide is administered to subjects<br>Drug: AMG 102<br>* AMG 102 is administered to subjects<br>Drug: Carboplatin<br>* Carboplatin is administered to some subjects in combination<br>Drug: Cisplatin<br>* Cisplatin is administered to some subjects in combination<br>|
| Placebo Comparator: ARM C<br>Blinded placebo and carboplatin or cisplatin and etoposide | Drug: Etoposide<br>* Etoposide is administered to subjects<br>Drug: Placebo<br>* Placebo is administered with Carboplatin and Etoposide<br>Drug: Carboplatin<br>* Carboplatin is administered to some subjects in combination<br>Drug: Cisplatin<br>* Cisplatin is administered to some subjects in combination<br>|
| Active Comparator: ARM A<br>Blinded AMG 479 study drug and carboplatin or cisplatin and etoposide | Drug: AMG 479<br>* AMG 479 is administered to subjects<br>Drug: Etoposide<br>* Etoposide is administered to subjects<br>Drug: Carboplatin<br>* Carboplatin is administered to some subjects in combination<br>Drug: Cisplatin<br>* Cisplatin is administered to some subjects in combination<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 2: To estimate the relative treatment effect of platinum-based chemotherapy and AMG 479, and of platinum-based chemotherapy and AMG 102, compared to platinum-based chemotherapy and placebo as measured by the respective HR for overall survival |  | Length of study | 
| Part 1: The incidence of adverse events and clinical laboratory abnormalities defined as dose limiting toxicities (DLTs). Part 2: Overall survival (OS) |  | Length of study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events and laboratory abnormalities not defined as DLTs. |  | Length of study | 
| Incidence of anti-AMG 479 and anti-AMG 102 antibody formation |  | Length of study | 
| Pharmacokinetics (Cmax and Cmin for AMG 102 and AMG 479) |  | Length of study | 
| ORR, DOR, TTP, PFS and OS rates at 10, 12, 24 and 36 months |  | Length of study | 
| EORTC QLQ-C30 and EORTC QLQ-LC13 scores |  | Length of study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Extensive disease, Extrathoracic metasasis, Malignant pericardial effusion, Malignant pleural effusion, Contralateral hilar adenopathy