Study of RXDX-105, Potent RET Inhibitor in Patients With Advanced Lung Cancer and Other Solid Tumors
- Registration Number
- NCT01877811
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This is a first-in-human, multicenter, open-label study consisting of 2 phases. Phase 1 is a dose escalation study of RXDX-105 (formerly known as CEP-32496) in patients with advanced solid tumors aimed at defining the recommended Phase 2 dose (RP2D) and schedule for administration. Phase 1b is a dose expansion in approximately 90 patients with advanced solid tumors with specific histologies and/or molecular alterations of interest. Patients in Phase 1b will be treated at the RP2D determined in Phase 1.
- Detailed Description
The primary objective of Phase 1 is to determine the recommended Phase 2 dose (RP2D) of RXDX-105. The primary objective of Phase 1b is to further assess the safety profile and tolerability of RXDX-105 at the RP2D The secondary objective is to evaluate the antitumor activity of RXDX-105 at the RP2D, as assessed by objective response rate (ORR) (complete response \[CR\] or partial response \[PR\]) using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) in patients with advanced solid tumors with RET or BRAF mutations or rearrangements.
The RP2D has been determined and Phase 1 portion of the study is now closed to new patient enrollment.
Phase 1 b is open and enrolling patients with solid tumors harboring a RET rearrangement or mutation, or a BRAF rearrangement or mutation. Additionally, patients with Squamous NSCLC and lung adenocarcinomas with other alterations than RET or BRAF such as KRAS mutations, etc. will also be enrolled. Approximately 90 patients will be enrolled in Phase 1b.
Each phase of this study will consist of a 28-day screening period. Patients will be treated in 28-day treatment cycles until documented radiographic progression, unacceptable toxicity, withdrawal of consent, or protocol specified parameters to stop treatment. Patients in Phase 1 and 1b will be followed for 6 months after the last dose of study treatment.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 143
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description RXDX-105 RXDX-105 -
- Primary Outcome Measures
Name Time Method Phase 1: Dose Limiting Toxicities Approximately 12 months From signing of the informed consent up to approximately 12 months
Phase 1: Occurrence of Adverse Events Approximately 12 months From signing of the informed consent up to approximately 12 months
Phase 1b: Occurrence of Adverse Events Approximately 12 months To further assess the safety profile and tolerability of RXDX-105 at the RP2D
- Secondary Outcome Measures
Name Time Method Phase 1: Terminal elimination half-life (t1/2) Day 1 to Day 16 Phase 1: Area under the plasma drug concentration versus time curve from time 0 to the last measureable drug concentration (AUC0-t) Day 1 to Day 16 Phase 1: Terminal elimination rate constant (λz) Day 1 to Day 16 Phase 1: Apparent clearance of study drug from plasma (CL/F) Day 1 to Day 16 Phase 1b: Objective Response Rate Approximately 12 months Objective response rate is defined as the proportion of patients with advanced solid tumors achieving best overall response of complete response (CR), or partial response (PR), as assessed using RECIST v1.1
Phase 1b: Duration of Objective Response Approximately 12 months The duration of objective response is defined as the time interval from the date of first documented response (CR or PR) to disease progression or death, whichever occurs first
Phase 1b: Clinical Benefit Rate Approximately 12 months Clinical benefit rate is defined as the proportion of patients achieving a complete response (CR), partial response (PR) or stable disease (SD) for 6 months
Phase 1: Maximum observed plasma drug concentration (Cmax) Day 1 to Day 16 Phase 1: Time of maximum observed plasma drug concentration (tmax) Day 1 to Day 16 Phase 1: Area under the plasma drug concentration versus time curve from time 0 to infinity (AUC0-∞) Day 1 to Day 16 Phase 1: Area under the plasma drug concentration versus time curve from time 0 to 24 hours after study drug administration (AUC0-24) Day 1 to Day 16
Trial Locations
- Locations (14)
Lombardi Comprehensive Cancer Center, Georgetown
🇺🇸Washington, District of Columbia, United States
City of Hope
🇺🇸Duarte, California, United States
University Cancer & Blood Center, LLC
🇺🇸Athens, Georgia, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
University of California San Diego Moores Cancer Center
🇺🇸San Diego, California, United States
Florida Cancer Center
🇺🇸Sarasota, Florida, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Karmanos Cancer Center
🇺🇸Detroit, Michigan, United States
Massachusetts General Hospital/Beth Israel Deaconess Med. Ctr./Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
University of Washington, Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
University of California Irvine College of Medicine
🇺🇸Irvine, California, United States
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States