A Study of RO5083945 in Combination With Chemotherapy Versus Chemotherapy Alone in Patients With Advanced or Recurrent Non-Small Cell Lung Cancer

A Randomized, Multicenter, Open-label Phase Ib/II Study of RO5083945 in Combination With Cisplatin and Gemcitabine/Pemetrexed Versus Cisplatin and Gemcitabine/Pemetrexed in Patients With Advanced or Recurrent Non Small Cell Lung Cancer Who Have Not Received Prior Chemotherapy

This open label, 2-part study will evaluate the safety and efficacy of RO5083945 in combination with standard chemotherapy in patients with advanced or recurrent non-small cell lung cancer who have not received prior chemotherapy. In Part 1 patients will receive RO5083945 intravenously and standard chemotherapy (cisplatin plus either gemcitabine or pemetrexed) for up to 6 cycles of 3 weeks and then RO5083945 until disease progression. In Part 2 patients will be randomized to receive either RO5083945 in combination with standard chemotherapy or chemotherapy alone for up to 6 cycles. In the absence of disease progression, patients receiving RO503945 can continue treatment with RO5083945 as monotherapy.

Study Overview

• Status: Completed
• Conditions: Non-Squamous Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: RO5083945; Drug: cisplatin; Drug: pemetrexed; Drug: gemcitabine

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Charleroi, Belgium, B6000
  • Leuven, Belgium, 3000
  • Liège, Belgium, 4000
• France
  • Caen, France, 14033
  • Marseille, France, 13915
  • Saint Herblain, France, 44805
  • Toulouse, France, 31400
• Germany
  • Bad Berka, Germany, 99437
  • Gauting, Germany, 82131
  • Grosshansdorf, Germany, 22927
  • Heidelberg, Germany, 69126
  • Köln, Germany, 51109
  • Mainz, Germany, 55131
  • Mannheim, Germany, 68167
• Italy
  • Lombardia
    • Milan, Lombardia, Italy, 20132
    • Milano, Lombardia, Italy, 20162
  • Marche
    • Ancona, Marche, Italy
  • Toscana
    • Lido Di Camaiore, Toscana, Italy, 55043
    • Livorno, Toscana, Italy, 57100
  • Umbria
    • Perugia, Umbria, Italy, 06156
• Poland
  • Lodz, Poland, 93-509
  • Otwock, Poland, 05-400
  • Warszawa, Poland, 02-781
• Spain
  • Barcelona, Spain, 08003
  • Barcelona, Spain, 08035
  • Madrid, Spain, 28040
  • Madrid, Spain, 28046
  • Madrid, Spain, 28041
  • Madrid, Spain, 28050
  • Malaga, Spain, 29010
  • Sevilla, Spain, 41013
• United Kingdom
  • London, United Kingdom, SE1 9RT

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
• Advanced (IIIb), metastatic (IV) or recurrent non-small cell lung cancer
• At least 1 measurable disease lesion as per RECIST criteria
• Confirmed presence of EGFR in tumor tissue
• ECOG performance status 0-1
• Adequate hematological, renal and liver function

Exclusion Criteria:

• Prior chemotherapy or treatment with another systemic anti-cancer agent
• Radiotherapy within the last 4 weeks, except for limited field palliative radiotherapy for bone pain relief
• Symptomatic or active CNS metastases
• Recent history of poorly controlled hypertension (systolic >180mmHg or diastolic >100mmHg)
• Requirement for steroids > 40 mg prednisolone

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A non-squamous	Drug: RO5083945; intravenously, until disease progression; Drug: cisplatin; standard treatment, up to 6 cycles; Drug: pemetrexed; standard treatment, up to 6 cycles
Experimental: A squamous	Drug: RO5083945; intravenously, until disease progression; Drug: cisplatin; standard treatment, up to 6 cycles; Drug: gemcitabine; standard treatment, up to 6 cycles
Active Comparator: B non-squamous	Drug: cisplatin; standard treatment, up to 6 cycles; Drug: pemetrexed; standard treatment, up to 6 cycles
Active Comparator: B squamous	Drug: cisplatin; standard treatment, up to 6 cycles; Drug: gemcitabine; standard treatment, up to 6 cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Part 2: Progression-free survival, according to RECIST criteria by CT/MRI	23 months
Part 1: Adverse event profile: adverse events, ECG, hematology, urinalysis, human anti-human antibodies (HAHA)	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics of RO5083945 (AUC, Cmax and Cmin) in combination with cisplatin and gemcitabine/pemetrexed	multiple sampling cycles 1-6 (18 weeks)
Duration of response, according to RECIST criteria by CT/MRI	from response to disease progression
Clinical benefit rate (complete response, partial response or stable disease for >/=6 weeks), according to RECIST criteria by CT/MRI	23 months
Overall survival	23 months
Overall response rate (ORR), according to RECIST criteria by CT/MRI	23 months

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: August 19, 2010
• First Submitted That Met QC Criteria: August 19, 2010
• First Posted (Estimate): August 20, 2010

Study Record Updates

• Last Update Posted (Estimate): January 1, 2016
• Last Update Submitted That Met QC Criteria: December 31, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Folic Acid Antagonists; Gemcitabine; Pemetrexed
• Other Study ID Numbers: BP22349; 2010-018945-72