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.
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
Drug | Synonyms | Arms |
---|
Entrectinib | RXDX-101 | ALK- or ROS1-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
Name | Type | Description | Interventions |
---|
NTRK1/2/3-rearranged NSCLC | Experimental | Oral entrectinib (RXDX-101) | |
ROS1-rearranged NSCLC | Experimental | Oral entrectinib (RXDX-101) | |
ALK- or ROS1-rearranged NSCLC | Experimental | with CNS-only progression previously treated with crizotinib (NOTE: The ALK-rearranged portion of this arm is now closed to enrollment.)
Oral entrectinib (RXDX-101) | |
NTRK/1/2/3-rearranged mCRC | Experimental | Oral entrectinib (RXDX-101) | |
ROS1-rearranged mCRC | Experimental | Oral entrectinib (RXDX-101) | |
ALK-rearranged mCRC | Experimental | Oral entrectinib (RXDX-101) | |
NTRK1/2/3-rearranged other solid tumor | Experimental | Oral entrectinib (RXDX-101) | |
ROS1-rearranged other solid tumor | Experimental | Oral entrectinib (RXDX-101) | |
ALK-rearranged other solid tumor | Experimental | Oral entrectinib (RXDX-101) | |
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
- 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
- Familial or personal history of congenital bone disorders, or bone metabolism
alterations
- Incomplete recovery from any surgery
- History of recent (within the past 3 months) symptomatic congestive heart failure or
ejection fraction ≤50% observed during screening for the study
- History of non-pharmacologically induced prolonged QTc interval
- History of additional risk factors for torsades 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 |
Measure: | Population PK |
Time Frame: | Approximately 24 months |
Safety Issue: | |
Description: | Assessed by Kaplan-Meier method |
Measure: | Adverse Events |
Time Frame: | Approximately 36 months |
Safety Issue: | |
Description: | Type, incidence, severity, timing, seriousness, and relatedness of adverse events and laboratory abnormalities, graded by the NCI CTCAE |
Measure: | Quality of Life |
Time Frame: | Approximately 24 months |
Safety Issue: | |
Description: | Assessed with the European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30) and the Euro-QoL Group EQ-5D. NSCLC and mCRC patients will complete the lung cancer and colorectal cancer specific modules, QLQ-LC13 and QLQ-CR29, respectively |
Measure: | Bone Growth and Bone Mineral Density |
Time Frame: | Approximately 30 months |
Safety Issue: | |
Description: | Assessed with DHA scans |
Measure: | Bone Biomarkers |
Time Frame: | Approximately 30 months |
Safety Issue: | |
Description: | Measured by blood |
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
Last Updated
August 30, 2021