Clinical Trial 18503

Cancer Type: Thoracic
Interventions:Entrectinib

Study Type: Treatment
Phase of Study: Phase II
Investigators:

  • Christine Chung

Overview

Study Title

STARTRK-2: An Open-Label, Multicenter, Global Phase 2 Basket Study of Entrectinib for the Treatment of Patients with Locally Advanced or Metastatic Solid Tumors that Harbor NTRK1/2/3, ROS1, or ALK Gene Rearrangements

Summary

This study will evaluate the safety (side effects) and antitumor activity of entrectinib in men and women with advanced cancer, based on certain types of DNA defect or damage.

Objective

Primary Objective: To determine the objective response rate (ORR) of entrectinib, as assessed by BICR, in each patient population basket of solid tumors that harbor an NTRK1/2/3, ROS1, or ALK gene rearrangement. Secondary Objectives: To determine the duration of response (DOR), time to response (TTR), and clinical benefit rate (CBR) of entrectinib, as assessed by BICR, in each patient population basket of solid tumors that harbor an NTRK1/2/3, ROS1, or ALK gene rearrangement. To determine the intracranial tumor response of entrectinib and CNS progression-free survival (CNS-PFS) in patients presenting with measurable brain metastases at baseline, as assessed by BICR using RANO-BM. To estimate the progression-free survival (PFS) and overall survival (OS) of patients with solid tumors that harbor anNTRK1/2/3, ROS1, or ALK gene rearrangement treated with entrectinib. To evaluate the safety and tolerability of entrectinib when administered at the RP2D in patients with solid tumors that harbor an NTRK1/2/3, ROS1, or ALK gene rearrangement. To assess the population pharmacokinetics (PK) of entrectinib and to explore correlations between PK, response, and/or safety findings in patients with NTRK1/2/3, ROS1, or ALK gene rearrangements. To evaluate the effect of entrectinib on ventricular repolarization in a subset of patients from selected countries. To assess treatment-related symptoms and general health status using validated instruments of patient reported outcomes.

Inclusion Criteria

  • Histologically- or cytologically-confirmed diagnosis of locally advanced or metastatic solid tumor that harbors an NTRK1/2/3, ROS1, or ALK gene rearrangement - Note: Patients diagnosed with anaplastic large cell lymphoma (ALCL) harboring a gene rearrangement of interest may be eligible provided they meet all other inclusion/exclusion criteria
  • For participants enrolled via local molecular testing, an archival or fresh tumor tissue (unless medically contraindicated) is required to be submitted for independent central molecular testing at Ignyta's CLIA laboratory post-enrollment
  • Measurable or evaluable disease
  • Patients with central nervous system (CNS) involvement, including leptomeningeal carcinomatosis, which is either asymptomatic or previously-treated and controlled, are allowed
  • Prior anticancer therapy is allowed (excluding approved or investigational Trk, ROS1, or ALK inhibitors in patients who have tumors that harbor those respective gene rearrangements) - Note: prior treatment with crizotinib is permitted in ALK- or ROS1-rearranged Non-small Cell Lung Cancer (NSCLC) patients presenting with CNS-only progression
  • At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed after prior chemotherapy or small molecule targeted therapy
  • At least 4 weeks must have elapsed since completion of antibody-directed therapy
  • Prior radiotherapy is allowed if more than 14 days have elapsed since the end of treatment
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 and minimum life expectancy of 4 weeks
  • Adequate organ function as defined per protocol
  • Ability to swallow entrectinib intact
  • Other protocol specified criteria

  • Exclusion Criteria

  • Current participation in another therapeutic clinical trial
  • Prior treatment with approved or investigational Trk, ROS1, or ALK inhibitors in patients who have tumors that harbor those respective gene rearrangements - Note: prior treatment with crizotinib is permitted in ALK- or ROS1-rearranged NSCLC patients presenting with CNS-only progression. Other ALK inhibitors are prohibited.
  • History of other previous cancer that would interfere with the determination of safety or efficacy
  • Incomplete recovery from any surgery
  • History of non-pharmacologically induced prolonged QTc interval
  • History of additional risk factors for torsade de pointes
  • Peripheral neuropathy Grade ≥ 2
  • Known active infections
  • Active gastrointestinal disease or other malabsorption syndromes
  • Known interstitial lung disease, interstitial fibrosis, or history of tyrosine kinase inhibitor-induced pneumonitis
  • Other protocol specified criteria