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)

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