Squamous Non-Small Cell Lung Cancer
Conditions
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.
Interventions
DRUGCarboplatin
Carboplatin by intravenous infusion q3w for 4-6 cycles and thereafter as per investigator's discretion.
DRUGPaclitaxel
Paclitaxel by intravenous infusion q3w until disease progression, death, unacceptable toxicity or withdrawal of consent.
DRUGRO5479599
RO5479599 will be administered as an intravenous infusion q3w until disease progression, death, unacceptable toxicity or withdrawal of consent.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
| Trough Concentration (Ctrough) of RO5479599 | Pre-dose (Hour 0) on Day 1 of each cycle (cycle length = 21 days) up to EOT (Day 314) |
| 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 |
| 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 |
| 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) |
| 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 Toxicity | At the time of toxicity (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) |
| 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 |
| 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) |
Countries
Canada, Denmark, Spain
Outcome results
None listed