A Study of RO5083945 in Combination With Cisplatin and Gemcitabine or Carboplatin and Paclitaxel in Patients With Advanced or Recurrent Non-Small Cell Lung Cancer of Squamous Histology Who Have Not Received Prior Chemotherapy for The Metastatic Disease

A MULTICENTER, OPEN-LABEL PHASE IB STUDY OF RO5083945 IN COMBINATION WITH CISPLATIN AND GEMCITABINE OR CARBOPLATIN AND PACLITAXEL IN PATIENTS WITH ADVANCED OR RECURRENT NON SMALL CELL LUNG CANCER OF SQUAMOUS HISTOLOGY WHO HAVE NOT RECEIVED PRIOR CHEMOTHERAPY FOR THE METASTATIC DISEASE.

This open-label, multicenter, non-randomized, dose-escalating phase Ib study with an expansion cohort will determine the recommended Phase II dose and schedule to investigate safety, tolerability, and activity of RO5083945 in combination with cisplatin and gemcitabine or carboplatin and paclitaxel in patients with advanced or recurrent non-small cell lung cancer of squamous histology who have not received prior chemotherapy for the metastatic disease. Cohorts of patients will receive escalating doses of RO5083945 in combination with up to 6 cycles of cisplatin and gemcitabine or carboplatin and paclitaxel. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.

Study Overview

• Status: Withdrawn
• Conditions: Non-Squamous Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: RO5083945; Drug: carboplatin; Drug: paclitaxel; Drug: cisplatin; Drug: gemcitabine

• Study Type: Interventional
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients, >/= 18 years of age
• Locally advanced (stage IIIB, excluding patients who are candidates for chemo-radiotherapy or radical thoracic radiotherapy), metastatic (stage IV) or recurrent squamous non-small cell lung cancer (NSCLC)
• Histologically documented squamous NSCLC. Mixed tumors should be categorized according to the predominant cell type
• Histological tumor tissue sample from initial diagnosis or new tumor biopsy representative of the disease
• Patients who have received adjuvant chemotherapy are eligible if the last administration of the prior adjuvant regimen occurred at least 3 months prior to enrollment
• At least one measurable disease lesion as per RECIST 1.1 criteria
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Adequate hematological, liver and renal function
• Females of childbearing potential must commit to using a reliable and appropriate method of contraception until at least 3 months after the end of the last dose of study treatment

Exclusion Criteria:

• Prior chemotherapy (excluding neoadjuvant/adjuvant chemotherapy/chemo-radiotherapy) or treatment with another systemic anti-cancer agent (e.g. monoclonal antibody, tyrosine kinase inhibitor)
• Radiotherapy within the last 4 weeks prior to first dosing, except for limited field palliative radiotherapy for bone pain relief
• Treatment with any other investigational agent within 30 days prior to starting study treatment or participation in another clinical trial (e.g. CTC blood collection) within 7 days prior to starting study treatment
• Historical or clinical evidence of central nervous system (CNS) metastases (except for previously treated CNS metastases in patients that are asymptomatic, have had no evidence of active CNS metastases for >/= 3 months prior to first dose and have had no requirement for steroids or enzyme-inducing anticonvulsants in the last 14 days)
• Recent history of poorly controlled hypertension (systolic >180 mmHg or diastolic >100 mmHg)
• Severe uncontrolled illness, including poorly controlled diabetes mellitus and active or uncontrolled infection
• Hypersensitivity to the active substance or to any excipients or to any of the study drugs including premedication (corticosteroids, anti-histamine, paracetamol)
• Pregnant or breastfeeding women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RO5083945 + carboplatin + paclitaxel	Drug: RO5083945; multiple ascending doses; Drug: carboplatin; up to 6 cycles; Drug: paclitaxel; up to 6 cycles
Experimental: RO5083945 + cisplatin +gemcitabine	Drug: RO5083945; multiple ascending doses; Drug: cisplatin; up to 6 cycles; Drug: gemcitabine; up to 6 cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum tolerated dose in combination with cisplatin and gemcitabine or carboplatin and paclitaxel	approximately 1.5 years
Recommended phase II dose (RP2D) of RO5083945 in combination with cisplatin and gemcitabine or carboplatin and paclitaxel	approximately 1.5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety: Incidence of adverse events	approximately 1.5 years
Pharmacokinetics: Serum concentrations of RO5083945 in combination with cisplatin and gemcitabine or carboplatin and paclitaxel	up to 18 weeks
Pharmacokinetics: Effect of RO5083945 on serum concentrations of cisplatin	up to 18 weeks
Pharmacokinetics: Effect of RO5083945 on serum concentrations of gemcitabine	up to 18 weeks
Pharmacokinetics: Effect of RO5083945 on serum concentrations of carboplatin	up to 18 weeks
Pharmacokinetics: Effect of RO5083945 on serum concentrations of paclitaxel	up to 18 weeks
Preliminary evidence of antitumor activity: Objective response rate (complete response, partial response and stable disease)	approximately 1.5 years
Duration of response	approximately 1.5 years
Biomarker assessments : Immune effector cells/EGFR markers	up to 18 weeks

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: July 1, 2014
• Primary Completion (Anticipated): February 1, 2016
• Study Completion (Anticipated): February 1, 2016

Study Registration Dates

• First Submitted: October 1, 2012
• First Submitted That Met QC Criteria: October 5, 2012
• First Posted (Estimate): October 8, 2012

Study Record Updates

• Last Update Posted (Estimate): November 4, 2016
• Last Update Submitted That Met QC Criteria: November 3, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neoplastic Processes; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Gemcitabine; Carboplatin; Paclitaxel; Cisplatin
• Other Study ID Numbers: BP28577; 2012-003376-39 (EudraCT Number)