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Basket Study of Entrectinib (RXDX-101) for the Treatment of Patients With Solid Tumors Harboring NTRK 1/2/3 (Trk A/B/C), ROS1, or ALK Gene Rearrangements (Fusions)

NCT02568267

Description:

This is an open-label, multicenter, global Phase 2 basket study of entrectinib (RXDX-101) for the treatment of patients with solid tumors that harbor an NTRK1/2/3, ROS1, or ALK gene fusion. Patients will be assigned to different baskets according to tumor type and gene fusion.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Basket Study of Entrectinib (RXDX-101) for the Treatment of Patients With Solid Tumors Harboring NTRK 1/2/3 (Trk A/B/C), ROS1, or ALK Gene Rearrangements (Fusions)
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: RXDX-101-02
  • SECONDARY ID: 2015‐003385‐84
  • SECONDARY ID: GO40782
  • NCT ID: NCT02568267

Conditions

  • Breast Cancer
  • Cholangiocarcinoma
  • Colorectal Cancer
  • Head and Neck Neoplasms
  • Lymphoma, Large-Cell, Anaplastic
  • Melanoma
  • Neuroendocrine Tumors
  • Non-Small Cell Lung Cancer
  • Ovarian Cancer
  • Pancreatic Cancer
  • Papillary Thyroid Cancer
  • Primary Brain Tumors
  • Renal Cell Carcinoma
  • Sarcomas
  • Salivary Gland Cancers
  • Adult Solid Tumor

Interventions

DrugSynonymsArms
EntrectinibRXDX-101NTRK1/2/3-rearranged NSCLC

Purpose

This is an open-label, multicenter, global Phase 2 basket study of entrectinib (RXDX-101) for the treatment of patients with solid tumors that harbor an NTRK1/2/3, ROS1, or ALK gene fusion. Patients will be assigned to different baskets according to tumor type and gene fusion.

Trial Arms

NameTypeDescriptionInterventions
NTRK1/2/3-rearranged NSCLCExperimentalOral entrectinib (RXDX-101)
  • Entrectinib
ROS1-rearranged NSCLCExperimentalOral entrectinib (RXDX-101)
  • Entrectinib
ALK- or ROS1-rearranged NSCLCExperimentalwith CNS-only progression previously treated with crizotinib Oral entrectinib (RXDX-101)
  • Entrectinib
NTRK/1/2/3-rearranged mCRCExperimentalOral entrectinib (RXDX-101)
  • Entrectinib
ROS1-rearranged mCRCExperimentalOral entrectinib (RXDX-101)
  • Entrectinib
ALK-rearranged mCRCExperimentalOral entrectinib (RXDX-101)
  • Entrectinib
NTRK1/2/3-rearranged other solid tumorExperimentalOral entrectinib (RXDX-101)
  • Entrectinib
ROS1-rearranged other solid tumorExperimentalOral entrectinib (RXDX-101)
  • Entrectinib
ALK-rearranged other solid tumorExperimentalOral entrectinib (RXDX-101)
  • Entrectinib

Eligibility Criteria

        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 patients 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 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 only in ALK- or ROS1-rearranged
             NSCLC patients presenting with CNS-only progression. Other ALK inhibitors are
             prohibited.

          -  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 only 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate
Time Frame:Approximately 24 months
Safety Issue:
Description:Assessed by blinded independent central review (BICR) using RECIST v1.1

Secondary Outcome Measures

Measure:Duration of Response
Time Frame:Approximately 24 months
Safety Issue:
Description:Assessed by blinded independent central review (BICR) using RECIST v1.1
Measure:Time to Response
Time Frame:Approximately 24 months
Safety Issue:
Description:Assessed by blinded independent central review (BICR) using RECIST v1.1
Measure:Clinical Benefit Rate
Time Frame:Approximately 24 months
Safety Issue:
Description:Assessed by blinded independent central review (BICR) using RECIST v1.1
Measure:Intracranial Tumor Response
Time Frame:Approximately 24 months
Safety Issue:
Description:Assessed by blinded independent central review (BICR) using RANO or RANO-BM, as applicable
Measure:CNS Progression-free Survival
Time Frame:Approximately 24 months
Safety Issue:
Description:Assessed by blinded independent central review (BICR) using RANO or RANO-BM, as applicable
Measure:Progression-free Survival
Time Frame:Approximately 30 months
Safety Issue:
Description:Assessed by Kaplan-Meier method
Measure:Overall Survival
Time Frame:Approximately 36 months
Safety Issue:
Description:Assessed by Kaplan-Meier method

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Hoffmann-La Roche

Trial Keywords

  • Entrectinib
  • RXDX-101
  • TrkA
  • TrkB
  • TrkC
  • NTRK1
  • NTRK2
  • NTRK3
  • ROS1
  • ALK
  • Trk Fusions
  • NTRK Gene Rearrangements
  • ROS1 Fusions
  • ROS1 Gene Rearrangements
  • ALK Fusions
  • ALK Gene Rearrangements
  • Basket study
  • Non-small cell lung cancer
  • Colorectal cancer
  • Salivary gland cancers
  • Primary brain tumors
  • Melanoma
  • Sarcomas
  • Papillary thyroid cancer
  • Renal cell cancer
  • Pancreatic cancer
  • Breast cancer
  • Cholangiocarcinoma
  • Head & Neck cancers
  • Ovarian cancer
  • Neuroendocrine tumors
  • Anaplastic Large Cell Lymphoma

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