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

Non-Squamous Non-Small Cell Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01496742
• Other study ID #: GO27821
• Secondary ID: 2011-003719-42
• Status: Completed
• Phase: Phase 2
• First received: December 19, 2011
• Last updated: September 21, 2016
• Start date: April 2012
• Est. completion date: November 2015

Study information

• Verified date: September 2016
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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 study treatment is until disease progression or unacceptable toxicity occurs.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 259
• Est. completion date: November 2015
• Est. primary completion date: November 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 or chemoradiotherapy: a treatment-free interval of at least 12 months since last chemotherapy or chemoradiotherapy cycle

• Adequate tissue for central immunohistochemical (IHC) assay of Met receptor, and epidermal growth factor receptor (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 hepatocyte growth factor (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, unless that treatment is unavailable or refused by the patient

• 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 that was treated surgically with curative intent, localized prostate cancer that has been treated surgically with curative intent, 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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Squamous Non-Small Cell Lung Cancer

Intervention

Drug:
• Placebo
Matching RO5490258 (MetMAb) placebo iv, Day 1 of each 21-day cycle
• RO5490258
15 mg/kg iv, Day 1 of each 21-day cycle
• bevacizumab [Avastin]
15 mg/kg iv, Day 1 of each 21-day cycle
• cisplatin/carboplatin
standard dose iv, Day 1 of each 21-day cycle, 4 cycles
• paclitaxel
200 mg/m2 iv, Day 1 of each 21-day cycle, 4 cycles
• pemetrexed
500 mg/m2, Day 1 of each 21-day cycle

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Countries where clinical trial is conducted

United States,  Argentina,  France,  Germany,  Israel,  Italy,  Latvia,  Malaysia,  Mexico,  Philippines,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival (tumor assessments according to RECIST criteria)		up to approximately 23 months	No
Primary	Progression-free survival: Subgroup of patients with Met diagnostic positive tumors		up to approximately 23 months	No
Secondary	Overall survival		up to approximately 23 months	No
Secondary	Overall response rate (tumor assessments according to RECIST criteria)		up to approximately 23 months	No
Secondary	Duration of response (time from first documented objective response to disease progression)		up to approximately 23 months	No
Secondary	Disease control rate (rate of partial response plus complete response plus stable disease for at least 6 weeks)		up to approximately 23 months	No
Secondary	Safety: Incidence of adverse events		up to approximately 23 months	No
Secondary	Pharmacokinetics: serum concentration (Cmin/Cmax)		Pre- and post-dose on Day 1 of Cycles 1, 2 and 4 and at study termination	No
Secondary	Serum concentrations of bevacizumab/paclitaxel/pemetrexed/platinum in combination with MetMAb		Pre- and post-dose on Day 1 of Cycles 1 and 4	No
Secondary	Serum levels of anti-therapeutic antibodies (MetMAb ATAs)		Pre-dose Day 1 of Cycles 1, 2 and 4	No