Active, not recruiting
Phase 2
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)
Condition(s) studied
Breast CancerCholangiocarcinomaColorectal CancerHead and Neck NeoplasmsLymphoma, Large-Cell, AnaplasticMelanomaNeuroendocrine TumorsNon-Small Cell Lung CancerOvarian CancerPancreatic CancerPapillary Thyroid CancerPrimary Brain TumorsRenal Cell CarcinomaSarcomasSalivary Gland CancersAdult Solid Tumor
Investigational drug(s) / intervention(s)
Entrectinib
Entrectinib: TrkA/B/C, ROS1, and ALK inhibitor
Study 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.
Eligibility
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
Primary outcome measure(s)
- Objective Response Rate — Approximately 24 months
Assessed by blinded independent central review (BICR) using RECIST v1.1
Trial sites (120)
| Facility | City | Region | Status |
| Dignity Health St Joseph's Hospital and Medical Center |
Phoenix |
Arizona |
|
| Mayo Clinic |
Phoenix |
Arizona |
|
| City of Hope Cancer Center |
Duarte |
California |
|
| City of Hope Duarte - Comprehensive Cancer Center, Investigational Drug Services |
Duarte |
California |
|
| Scripps Clinic |
La Jolla |
California |
|
| University of California San Diego Moores Cancer Center |
La Jolla |
California |
|
| Southern California Kaiser Permanente |
Los Angeles |
California |
|
| Univ Of California Irvine College Of Medicine |
Orange |
California |
|
| UCSF Mount Zion Medical Ctr |
San Francisco |
California |
|
| UCSF Mission Bay |
San Francisco |
California |
|
| Sarcoma Oncology Center |
Santa Monica |
California |
|
| Sarcoma Oncology Research Center LLC |
Santa Monica |
California |
|
| University of Colorado Cancer Center |
Aurora |
Colorado |
|
| Yale University |
New Haven |
Connecticut |
|
| Georgetown University Medical Center Lombardi Cancer Center |
Washington D.C. |
District of Columbia |
|
| Florida Cancer Specialists - Sarasota |
Sarasota |
Florida |
|
| H. Lee Moffitt Cancer Center and Research Inst. |
Tampa |
Florida |
|
| Moffitt Cancer Center |
Tampa |
Florida |
|
| University Cancer & Blood Center, LLC |
Athens |
Georgia |
|
| Winship Cancer Institute |
Atlanta |
Georgia |
|
| Southeastern Regional Medical Center, Inc. |
Newnan |
Georgia |
|
| Northwestern University |
Chicago |
Illinois |
|
| Advocate Medical Group - Park Ridge, Luther Lane - Oncology |
Park Ridge |
Illinois |
|
| Midwestern Regional Medical Center |
Zion |
Illinois |
|
| Weinberg Cancer Institution at Franklin Square |
Baltimore |
Maryland |
|
| Massachusetts General Hosp CAR |
Boston |
Massachusetts |
|
| Massachusetts General Hospital |
Boston |
Massachusetts |
|
| Beth Israel Deaconess Medical Center |
Boston |
Massachusetts |
|
| Dana Farber Cancer Institute |
Boston |
Massachusetts |
|
| Karmanos Cancer Center |
Detroit |
Michigan |
|
| Henry Ford Hospital |
Detroit |
Michigan |
|
| Regents of the University of Minnesota |
Minneapolis |
Minnesota |
|
| Washington University |
St Louis |
Missouri |
|
| Comprehensive Cancer Centers of Nevada (CCCN) - Central Valley |
Las Vegas |
Nevada |
|
| North Shore Hem Onc Associates |
East Setauket |
New York |
|
| Memorial Sloan Kettering Cancer Center |
New York |
New York |
|
| Atrium Health Levine Cancer Institute |
Charlotte |
North Carolina |
|
| Levine Cancer Institute |
Charlotte |
North Carolina |
|
| Duke Cancer Institute |
Durham |
North Carolina |
|
| Ohio State University |
Columbus |
Ohio |
|
+ 80 more sites — see the full list on the official registry below.