A Study of Onartuzumab (MetMAb) in Combination With Bevacizumab (Avastin) Plus Platinum And Paclitaxel or With Pemetrexed Plus Platinum in Patients With Non-Squamous Non-Small Cell Lung Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Genentech
ClinicalTrials.gov Identifier:
NCT01496742
First received: December 19, 2011
Last updated: April 14, 2014
Last verified: April 2014
  Purpose

This multicenter, randomized, double-blind, placebo-controlled study will evaluate the efficacy and safety of RO5490258 (MetMab) in combination with either of two backbone chemotherapy regimens in the first-line setting in patients with incurable Stage IIIB or IV non-squamous non-small cell lung cancer. In Cohort 1, patients will be randomized to receive 4 cycles of bevacizumab (Avastin) 15 mg/kg iv, paclitaxel 200 mg/m2 iv, platinum (cisplatin/carboplatin) iv plus either MetMab 15 mg/kg iv or placebo on Day 1 of each 21-day cycle. In Cohort 2, patients will be randomized to receive pemetrexed 500 mg/m2 iv, platinum (cisplatin/carboplatin) iv plus either MetMAb 15 mg/m2 iv or placebo on Day 1 of each 21-day cycle. Patients who have not progressed after 4 cycles will be offered maintenance therapy with their assigned treatment of bevacizumab plus either MetMAb or placebo (Cohort 1) or pemetrexed plus either MetMAb or placebo (Cohort 2). Anticipated time on st! udy treatment is until disease progression or unacceptable toxicity occurs.


Condition Intervention Phase
Non-Small Cell Lung Cancer
Drug: RO5490258
Drug: bevacizumab [Avastin]
Drug: pemetrexed
Drug: Placebo
Drug: cisplatin/carboplatin
Drug: paclitaxel
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Phase II, Multicenter, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Metmab Vs. Placebo in Combination With Either Bevacizumab + Platinum + Paclitaxel or Pemetrexed + Platinum in Patients With Untreated Stage IIIb or IV Non-Squamous NSCLC

Resource links provided by NLM:


Further study details as provided by Genentech:

Primary Outcome Measures:
  • Progression-free survival (tumor assessments according to RECIST criteria) [ Time Frame: up to approximately 23 months ] [ Designated as safety issue: No ]
  • Progression-free survival: Subgroup of patients with Met diagnostic positive tumors [ Time Frame: up to approximately 23 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: up to approximately 23 months ] [ Designated as safety issue: No ]
  • Overall response rate (tumor assessments according to RECIST criteria) [ Time Frame: up to approximately 23 months ] [ Designated as safety issue: No ]
  • Duration of response (time from first documented objective response to disease progression) [ Time Frame: up to approximately 23 months ] [ Designated as safety issue: No ]
  • Disease control rate (rate of partial response plus complete response plus stable disease for at least 6 weeks) [ Time Frame: up to approximately 23 months ] [ Designated as safety issue: No ]
  • Safety: Incidence of adverse events [ Time Frame: up to approximately 23 months ] [ Designated as safety issue: No ]
  • Pharmacokinetics: serum concentration (Cmin/Cmax) [ Time Frame: Pre- and post-dose on Day 1 of Cycles 1, 2 and 4 and at study termination ] [ Designated as safety issue: No ]
  • Serum concentrations of bevacizumab/paclitaxel/pemetrexed/platinum in combination with MetMAb [ Time Frame: Pre- and post-dose on Day 1 of Cycles 1 and 4 ] [ Designated as safety issue: No ]
  • Serum levels of anti-therapeutic antibodies (MetMAb ATAs) [ Time Frame: Pre-dose Day 1 of Cycles 1, 2 and 4 ] [ Designated as safety issue: No ]

Enrollment: 259
Study Start Date: April 2012
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bevacizumab+MetMAb Drug: RO5490258
15 mg/kg iv, Day 1 of each 21-day cycle
Drug: bevacizumab [Avastin]
15 mg/kg iv, Day 1 of each 21-day cycle
Drug: cisplatin/carboplatin
standard dose iv, Day 1 of each 21-day cycle, 4 cycles
Drug: paclitaxel
200 mg/m2 iv, Day 1 of each 21-day cycle, 4 cycles
Active Comparator: Bevacizumab+Placebo Drug: bevacizumab [Avastin]
15 mg/kg iv, Day 1 of each 21-day cycle
Drug: Placebo
Matching RO5490258 (MetMAb) placebo iv, Day 1 of each 21-day cycle
Drug: cisplatin/carboplatin
standard dose iv, Day 1 of each 21-day cycle, 4 cycles
Drug: paclitaxel
200 mg/m2 iv, Day 1 of each 21-day cycle, 4 cycles
Experimental: Pemetrexed+MetMAb Drug: RO5490258
15 mg/kg iv, Day 1 of each 21-day cycle
Drug: pemetrexed
500 mg/m2, Day 1 of each 21-day cycle
Drug: cisplatin/carboplatin
standard dose iv, Day 1 of each 21-day cycle, 4 cycles
Active Comparator: Pemetrexed+Placebo Drug: pemetrexed
500 mg/m2, Day 1 of each 21-day cycle
Drug: Placebo
Matching RO5490258 (MetMAb) placebo iv, Day 1 of each 21-day cycle
Drug: cisplatin/carboplatin
standard dose iv, Day 1 of each 21-day cycle, 4 cycles

  Eligibility

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

Inclusion Criteria:

  • Adult patients, >/= 18 years of age
  • Histologically or cytologically confirmed Stage IIIB or Stage IV non-squamous non-small cell lung cancer (NSCLC)
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • For patients who received prior adjuvant chemotherapy: a treatment-free interval of at least 12 months since last chemotherapy cycle
  • Adequate tissue for central IHC assay of Met receptor, and EGFR testing if EGFR status is unknown
  • Radiographic evidence of disease

Exclusion Criteria:

  • Prior systemic treatment for Stage IIIB or IV non-squamous NSCLC
  • Evidence of mixed NSCLC with a predominance of the squamous cell type
  • Prior exposure to experimental treatment targeting either the HGF or Met pathway
  • Patients with tumors confirmed to have EGFR-activating mutations who are suitable for anti-EGFR therapy (e.g. gefitinib or erlotinib), as determined by the investigator
  • Known central nervous system (CNS) disease, other than stable, treated brain metastases
  • History of another malignancy in the previous 3 years, except for history of in situ cancer or basal or squamous cell skin cancer
  • Uncontrolled diabetes
  • Pregnant or lactating women
  • Impaired bone marrow, liver or renal function (as defined by protocol)
  • Significant history of cardiovascular disease
  • Positive for HIV infection
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01496742

  Show 87 Study Locations
Sponsors and Collaborators
Genentech
Investigators
Study Director: Clinical Trials Genentech
  More Information

No publications provided

Responsible Party: Genentech
ClinicalTrials.gov Identifier: NCT01496742     History of Changes
Other Study ID Numbers: GO27821, 2011-003719-42
Study First Received: December 19, 2011
Last Updated: April 14, 2014
Health Authority: United States: Food and Drug Administration

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
Pemetrexed
Bevacizumab
Cisplatin
Carboplatin
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Folic Acid Antagonists
Antimetabolites, Antineoplastic
Antimetabolites
Angiogenesis Inhibitors

ClinicalTrials.gov processed this record on April 17, 2014