A Study Evaluating RO5479599 in Combination With Carboplatin and Paclitaxel in Participants With Advanced or Metastatic Non-Small-Cell Lung Cancer (NSCLC) of Squamous Histology

Phase 1

Terminated

• Conditions: Squamous Non-Small Cell Lung Cancer
• Interventions: Drug: Carboplatin; Drug: Paclitaxel; Drug: RO5479599

• Registration Number: NCT02204345
• Lead Sponsor: Hoffmann-La Roche

Brief Summary

A multi-center Phase Ib/II study of the combination of RO5479599 with carboplatin and paclitaxel once in every 3 week (q3w) regimen to evaluate the safety and tolerability.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-07-24
• Study First Submitted QC: 2014-07-29
• Study First Posted: 2014-07-30
• Study Start: 2014-10
• Primary Completion: 2016-03
• Study Completion: 2016-03
• Status Verified: 2017-01
• Disposition First Submitted: 2017-01-24
• Disposition First Submitted QC: 2017-01-24
• Last Update Submitted: 2017-01-24
• Disposition First Posted: 2017-01-25
• Last Update Posted: 2017-01-25

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

• Participants with the Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
• Locally advanced or metastatic (stage IIIB or IV) squamous NSCLC
• No prior systemic chemotherapy, targeted therapy for metastatic NSCLC
• Evidence of at least one radiologically measurable lesion as per RECIST version 1.1
• Adequate hematological, liver and renal function
• Participants must agree to either remain completely abstinent or to use effective contraceptive methods from screening until 6 months after the last dose of study treatment
• Histologically confirmed squamous NSCLC participants eligible for enrollment must provide archival tumor biopsy tissue or if unavailable must be willing to undergo a fresh pretreatment primary tumor or metastatic biopsy
• Participants with Gilbert's Syndrome will be eligible for the study

Read More

Exclusion Criteria

• Concurrent therapy with any other investigational drug
• History or clinical evidence of central nervous system (CNS) primary tumors or metastases
• Evidence of significant, uncontrolled concomitant diseases, which could affect compliance with the protocol or interpretation of results, including uncontrolled diabetes mellitus and/or significant cardiovascular disease or uncontrolled infection
• Any other diseases, metabolic dysfunction, a physical examination finding or a clinical laboratory finding, giving reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug
• Major surgery or significant traumatic injury less than (<) 28 days prior to the first study treatment infusion (excluding biopsies) or anticipation of the need for major surgery during study treatment
• Pregnant or breast-feeding women
• History of other malignancies that could affect compliance with protocol or interpretation of results. Participants with malignancies diagnosed more than 5 years prior to study day one, adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer are generally eligible

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
RO5479599 + Carboplatin + Paclitaxel	Paclitaxel	RO5479599 800 milligrams (mg) will be administered in the Safety Run-In Phase by intravenous infusion q3w on Day 1 of 3-weekly cycles (each cycle of 21 days) in combination with carboplatin (to produce an area under the curve \[AUC\] of 6 mg/milliliter \[mL\]\*minute) and paclitaxel 200 mg per square meter (mg/m\^2) by intravenous infusion q3w for 4 to 6 cycles. Thereafter, RO5479599 will be continued as a monotherapy (carboplatin and paclitaxel may be continued at the investigator's discretion) until disease progression, death, unacceptable toxicity, withdrawal of consent, or study termination by sponsor, whichever occurs first.
RO5479599 + Carboplatin + Paclitaxel	RO5479599	RO5479599 800 milligrams (mg) will be administered in the Safety Run-In Phase by intravenous infusion q3w on Day 1 of 3-weekly cycles (each cycle of 21 days) in combination with carboplatin (to produce an area under the curve \[AUC\] of 6 mg/milliliter \[mL\]\*minute) and paclitaxel 200 mg per square meter (mg/m\^2) by intravenous infusion q3w for 4 to 6 cycles. Thereafter, RO5479599 will be continued as a monotherapy (carboplatin and paclitaxel may be continued at the investigator's discretion) until disease progression, death, unacceptable toxicity, withdrawal of consent, or study termination by sponsor, whichever occurs first.
RO5479599 + Carboplatin + Paclitaxel	Carboplatin	RO5479599 800 milligrams (mg) will be administered in the Safety Run-In Phase by intravenous infusion q3w on Day 1 of 3-weekly cycles (each cycle of 21 days) in combination with carboplatin (to produce an area under the curve \[AUC\] of 6 mg/milliliter \[mL\]\*minute) and paclitaxel 200 mg per square meter (mg/m\^2) by intravenous infusion q3w for 4 to 6 cycles. Thereafter, RO5479599 will be continued as a monotherapy (carboplatin and paclitaxel may be continued at the investigator's discretion) until disease progression, death, unacceptable toxicity, withdrawal of consent, or study termination by sponsor, whichever occurs first.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Adverse Events	Baseline up to Day 342
Percentage of Participants With Objective Response as Assessed by Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)	Baseline until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurred first (assessed every 6 weeks from baseline [Cycle 1 Day 1] [Cycle length = 21 days] up to Day 342)

Secondary Outcome Measures

Name	Time	Method
Maximum Observed Plasma Concentration (Cmax) of RO5479599	Pre-dose (Hour 0) and at end of infusion (infusion duration=approximately 2 hours) on Day 1 of each cycle (cycle length= 21 days) up to EOT (Day 314); 3-6, 24, 72, 168, 264, 336, 432, 480 hours post-dose on Day 1 of Cycle 1,4; at Day 342
Total Clearance (CL) of RO5479599	Pre-dose (Hour 0) and at end of infusion (infusion duration=approximately 2 hours) on Day 1 of each cycle (cycle length= 21 days) up to EOT (Day 314); 3-6, 24, 72, 168, 264, 336, 432, 480 hours post-dose on Day 1 of Cycle 1,4; at Day 342
Concentration of RO5479599 at the Time of Toxicity	At the time of toxicity (anytime between baseline and Day 342)
Progression-free Survival (PFS) as Assessed Using RECIST v1.1	Baseline until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurred first (assessed every 6 weeks from baseline [Cycle 1 Day 1] [Cycle length = 21 days] up to Day 342)
Overall survival (OS)	Baseline until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurred first (assessed every 6 weeks from baseline [Cycle 1 Day 1] [Cycle length = 21 days] up to Day 342)
Percentage of Participants With Disease Control as Assessed by Investigator Using RECIST v1.1	Baseline until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurred first (assessed every 6 weeks from baseline [Cycle 1 Day 1] [Cycle length = 21 days] up to Day 342)
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of RO5479599	Pre-dose(Hour 0); at end of infusion (infusion duration=approximately 2 hours) on Day 1 of each cycle (cycle length= 21 days) up to end of treatment (EOT, Day 314); 3-6, 24, 72, 168, 264, 336, 432, 480 hours post-dose on Day 1 of Cycle 1,4; at Day 342
Volume of Distribution at Steady State (Vss) of RO5479599	Pre-dose (Hour 0) and at end of infusion (infusion duration=approximately 2 hours) on Day 1 of each cycle (cycle length= 21 days) up to EOT (Day 314); 3-6, 24, 72, 168, 264, 336, 432, 480 hours post-dose on Day 1 of Cycle 1,4; at Day 342
Trough Concentration (Ctrough) of RO5479599	Pre-dose (Hour 0) on Day 1 of each cycle (cycle length = 21 days) up to EOT (Day 314)
Accumulation Ratio (Rac) of RO5479599	Pre-dose(Hour 0); at end of infusion (infusion duration=approximately 2 hours) on Day 1 of each cycle (cycle length= 21 days) up to end of treatment (EOT, Day 314); 3-6, 24, 72, 168, 264, 336, 432, 480 hours post-dose on Day 1 of Cycle 1,4; at Day 342
Terminal Elimination Half-life (t 1/2) of RO5479599	Pre-dose(Hour 0); at end of infusion (infusion duration=approximately 2 hours) on Day 1 of each cycle (cycle length= 21 days) up to end of treatment (EOT, Day 314); 3-6, 24, 72, 168, 264, 336, 432, 480 hours post-dose on Day 1 of Cycle 1,4; at Day 342
Concentration of RO5479599 at the Time of Tumor Progression (Cprog)	At tumor progression (any time between Baseline and Day 342)
Concentration of RO5479599 at the Time of Tumor Response (Complete Response or Partial Response)	At the time of tumor response (anytime between baseline and Day 342)
Concentration of RO5479599 at the Time of Infusion-related Reactions (IRRs) or Hypersensitivity Reaction	At the time of IRRs or Hypersensitivity Reaction (anytime between baseline and Day 342)