Clinical trial NCT02204345: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Squamous Non-Small Cell Lung Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2014-07-30
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants With Adverse Events
timeFrame: Baseline up to Day 342
measure: Percentage of Participants With Objective Response as Assessed by Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
timeFrame: 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:
measure: Progression-free Survival (PFS) as Assessed Using RECIST v1.1
timeFrame: 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)
measure: Overall survival (OS)
timeFrame: 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)
measure: Percentage of Participants With Disease Control as Assessed by Investigator Using RECIST v1.1
timeFrame: 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)
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of RO5479599
timeFrame: 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
measure: Maximum Observed Plasma Concentration (Cmax) of RO5479599
timeFrame: 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
measure: Trough Concentration (Ctrough) of RO5479599
timeFrame: Pre-dose (Hour 0) on Day 1 of each cycle (cycle length = 21 days) up to EOT (Day 314)
measure: Total Clearance (CL) of RO5479599
timeFrame: 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
measure: Volume of Distribution at Steady State (Vss) of RO5479599
timeFrame: 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
measure: Accumulation Ratio (Rac) of RO5479599
timeFrame: 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
measure: Terminal Elimination Half-life (t 1/2) of RO5479599
timeFrame: 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
measure: Concentration of RO5479599 at the Time of Tumor Progression (Cprog)
timeFrame: At tumor progression (any time between Baseline and Day 342)
measure: Concentration of RO5479599 at the Time of Tumor Response (Complete Response or Partial Response)
timeFrame: At the time of tumor response (anytime between baseline and Day 342)
measure: Concentration of RO5479599 at the Time of Toxicity
timeFrame: At the time of toxicity (anytime between baseline and Day 342)
measure: Concentration of RO5479599 at the Time of Infusion-related Reactions (IRRs) or Hypersensitivity Reaction
timeFrame: At the time of IRRs or Hypersensitivity Reaction (anytime between baseline and Day 342)
Other outcomes:
Locations:
city: Toronto
country: Canada
state: Ontario
city: København Ø
country: Denmark
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Valencia
country: Spain
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: