Open Label Phase Ib/II, Multicenter Study of the Combination of RO5479599 With Carboplatin and Paclitaxel in Patients With Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) of Squamous Histology Who Have Not Received Prior Chemotherapy or Targeted Therapy for NSCLC
Trial Snapshot
- Phase
- Phase 1
- Status
- Terminated
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 12
- Primary Endpoint
- Percentage of Participants With Adverse Events
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
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
Arms & Interventions
RO5479599 + Carboplatin + 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.
Intervention: Carboplatin (Drug)
RO5479599 + Carboplatin + 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.
Intervention: Paclitaxel (Drug)
RO5479599 + Carboplatin + 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.
Intervention: RO5479599 (Drug)
Outcomes
Primary Outcomes
Percentage of Participants With Adverse Events
Time Frame: 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)
Time Frame: 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 Outcomes
- 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))