Study of RXDX-101 in Children With Recurrent or Refractory Solid Tumors and Primary CNS Tumors

This is a 4-part, open-label, Phase 1/1b, dose escalation study in pediatric patients with relapsed refractory solid tumors; 2) primary CNS tumors; 3) neuroblastoma; and 4) non-neuroblastoma, extracranial solid tumors with NTRK1/2/3, ROS1 or ALK gene rearrangements. The study is designed to explore the safety, maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D), pharmacokinetics, and antitumor activity of entrectinib.

Conducting Institutions:

Dana-Farber Cancer Institute, Children's Hospital Boston

Overall PI:

Site-responsible Investigators:

Contacts:

Eligibility Criteria

Inclusion Criteria:

  1. Ability to swallow capsules

  2. Body surface area (BSA): Subjects must have a body surface area ≥ 0.45 m2 at the time
     of the study enrollment

  3. Disease status: Subjects must have measurable or evaluable disease, by RECIST v1.1 ±
     Curie Scale Criteria

  4. Tumor type:

     Part A: Relapsed or refractory extracranial solid tumors Part B: Relapsed or
     refractory primary CNS tumors Part C: Relapsed or refractory neuroblastoma Part D:
     Relapsed or refractory non-neuroblastoma, extracranial solid tumors with NTRK1/2/3,
     ROS1, or ALK gene rearrangements documented by a CLIA-approved lab prior to
     enrollment

  5. Histologic/molecular diagnosis of malignancy at diagnosis or the time of relapse

  6. Archival tumor tissue from diagnosis or, preferably, at relapse

  7. Age: Male or female age ≥ 2 years and < 22 years

  8. Performance status: Lansky or Karnofsky score ≥ 60%

  9. Patient's cancer must have relapsed after or failed to respond to frontline curative
     therapy or there must not be other potentially curative treatment options available

 10. Adequate organ and neurologic function

 11. Females of child bearing potential must have a negative serum pregnancy test within
     14 days prior to entrectinib dosing

Exclusion Criteria:

  1. Receiving other experimental therapy

  2. Known congenital long QT syndrome

  3. Known active infections

  4. Receiving Enzyme Inducing Antiepileptic Drugs (EIAEDs) within 14 days of first dose.

  5. Incomplete recovery from acute effects of any surgery prior to treatment.

  6. Active gastrointestinal disease or other malabsorption syndromes that would impact
     drug absorption.

  7. Other severe acute or chronic medical or psychiatric condition or lab abnormality
     that may increase the risk associated with study participation, drug administration
     or may interfere with the interpretation of study results.