Adult Solid Tumor, 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, Salivary Gland Cancers, Sarcomas
Conditions
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
Brief summary
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.
Interventions
DRUGEntrectinib
TrkA/B/C, ROS1, and ALK inhibitor
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | Approximately 24 months | Assessed by blinded independent central review (BICR) using RECIST v1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response | Approximately 24 months | Assessed by blinded independent central review (BICR) using RECIST v1.1 |
| Time to Response | Approximately 24 months | Assessed by blinded independent central review (BICR) using RECIST v1.1 |
| Clinical Benefit Rate | Approximately 24 months | Assessed by blinded independent central review (BICR) using RECIST v1.1 |
| Intracranial Tumor Response | Approximately 24 months | Assessed by blinded independent central review (BICR) using RANO or RANO-BM, as applicable |
| CNS Progression-free Survival | Approximately 24 months | Assessed by blinded independent central review (BICR) using RANO or RANO-BM, as applicable |
| Progression-free Survival | Approximately 30 months | Assessed by Kaplan-Meier method |
| Overall Survival | Approximately 36 months | Assessed by Kaplan-Meier method |
| Population PK | Approximately 24 months | Assessed by Kaplan-Meier method |
| Adverse Events | Approximately 36 months | Type, incidence, severity, timing, seriousness, and relatedness of adverse events and laboratory abnormalities, graded by the NCI CTCAE |
| Quality of Life | Approximately 24 months | 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 |
| Bone Growth and Bone Mineral Density | Approximately 30 months | Assessed with DHA scans |
| Bone Biomarkers | Approximately 30 months | Measured by blood |
Countries
Australia, Belgium, China, France, Germany, Hong Kong, Italy, Japan, Netherlands, Poland, Singapore, South Korea, Spain, Taiwan, United Kingdom, United States
Contacts
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Outcome results
None listed