Study Of Entrectinib (Rxdx-101) in Children and Adolescents With Locally Advanced Or Metastatic Solid Or Primary CNS Tumors And/Or Who Have No Satisfactory Treatment Options
This is an open-label, Phase 1/2 multicenter dose escalation study in pediatric patients with relapsed or refractory extracranial solid tumors (Phase 1), with additional expansion cohorts (Phase 2) in patients with primary brain tumors harboring NTRK1/2/3 or ROS1 gene fusions, and extracranial solid tumors harboring NTRK1/2/3 or ROS1 gene fusions.
Eligibility
Sex
ALL
Min age
0 Years
Max age
18 Years
Healthy volunteers
No
Inclusion Criteria:
1. Disease status:
* Phase 1 portion (closed): Participants must have measurable or evaluable disease, as defined by RECIST v1.1
* Phase 2 portion:
* Part B: Participants must have measurable or evaluable disease, as defined by RANO
* Part C (closed): Participants must have measurable or evaluable disease, as defined by RECIST v1.1 ± Curie Scale
* Part D: Participants must have measurable or evaluable disease, as defined by RECIST v1.1
* Part E (closed): Participants must have measurable or evaluable disease, as defined by RECIST v1.1 ± Curie Scale or RANO
2. Tumor type:
* Phase 1 portion:
\* Part A: Relapsed or refractory extracranial solid tumors
* Phase 2 portion
* Part B: Primary brain tumors with NTRK1/2/3 or ROS1 gene fusions; gene fusions are defined as those predicted to translate into a fusion protein with a functional TRKA/B/C or ROS1 kinase domain, without a concomitant second oncodriver as determined by a nucleic acid-based diagnostic testing method
* Part D: Extracranial solid tumors (including NB) with NTRK1/2/3 or ROS1 gene fusions; gene fusions are defined as those predicted to translate into a fusion protein with a functional TRKA/B/C or ROS1 kinase domain, without a concomitant second oncodriver as determined by a nucleic acid-based diagnostic testing method
3. Histologic/molecular diagnosis of malignancy at diagnosis or the time of relapse
4. Archival tumor tissue from diagnosis or, preferably, at relapse
5. Performance status: Lansky or Karnofsky score ≥ 60% and minimum life expectancy of at least 4 weeks
6. Prior therapy: Participants must have a disease that is locally advanced, metastatic, or where surgical resection is likely to result in severe morbidity, and who have no satisfactory treatment options for solid tumors and primary CNS tumors that are neurotrophic tyrosine receptor kinase (NTRK) or ROS1 fusion-positive
7. Participants must have recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to enrollment
8. Adequate organ and neurologic function
9. Females of childbearing potential must have a negative serum pregnancy test during screening and be neither breastfeeding nor intending to become pregnant during study participation. Agreement to remain abstinent or use use combined contraceptive methods prior to study entry, for the duration of study participation and in the following 90 days after discontinuation of study treatment.
10. For male participants with a female partner of childbearing potential or a pregnant female partner: Agreement to remain abstinent or use a condom during the treatment period and for at least 3 months after the last dose of study drug
Exclusion Criteria:
1. Receiving other experimental therapy
2. Known congenital long QT syndrome
3. History of recent (3 months) symptomatic congestive heart failure or ejection fraction ≤50% at screening
4. Known active infections
5. Familial or personal history of congenital bone disorders, bone metabolism alterations or osteopenia
6. Receiving Enzyme Inducing Antiepileptic Drugs (EIAEDs) within 14 days of first dose.
7. Prior treatment with approved or investigational TRK or ROS1 inhibitors
8. Known hypersensitivity to entrectinib or any of the other excipients of the investigational medicinal product
9. Patients with NB with bone marrow space-only disease
10. Incomplete recovery from acute effects of any surgery prior to treatment.
11. Active gastrointestinal disease or other malabsorption syndromes that would impact drug absorption.
12. 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.
Primary outcome measure(s)
Maximum Tolerated Dose (MTD) — Approximately 6 months Assessed by National Cancer Institute Common Terminology for Adverse Events Criteria (NCI CTCAE v4.03)
Recommended Phase 2 Dose (RP2D) of F1 Formulation In Pediatric Participants Able To Swallow Intact Capsules — Approximately 6 months Assessed by NCI CTCAE v4.03
Recommended Phase 2 Dose (RP2D) of F06 Formulation In Pediatric Participants Able To Swallow Intact Capsules — Approximately 6 months Assessed by NCI CTCAE v4.03
Recommended Phase 2 Dose (RP2D) of F06 Formulation In Pediatric In Participants Dosed Via Feeding Tube (Nasogastric Tube Or Gastric Tube) — Approximately 6 months Assessed by NCI CTCAE v4.03
Recommended Phase 2 Dose (RP2D) Of Minitablets/F15 Formulation In Pediatric Participants Unable To Swallow Intact Capsules — Approximately 6 months Assessed by NCI CTCAE v4.03
Cohort B: Objective Response Rate (ORR) — Approximately 6 months Assessed by RANO per the BICR
Cohort D: ORR — Approximately 6 months Assessed by RECIST v1.1 per the BICR
Trial sites (26)
Facility
City
Region
Status
University of California San Diego
La Jolla
California
UCSF Benioff Children's Hospital
San Francisco
California
Children's Hospital Colorado
Aurora
Colorado
Egleston Children's Hospital at Emory University Atlanta
Atlanta
Georgia
University of Chicago
Chicago
Illinois
Johns Hopkins University
Baltimore
Maryland
Dana Farber Cancer Institute
Boston
Massachusetts
Washington University,St. Louis Children's Hospital
St Louis
Missouri
Memorial Sloan Kettering Cancer Center
New York
New York
Nationwide Children's Hospital
Columbus
Ohio
Oregon Health & Science Uni
Portland
Oregon
Children's Hospital of Philadelphia
Philadelphia
Pennsylvania
St. Jude Children'S Research Hospital
Memphis
Tennessee
Texas Children's Cancer and Hematology Center
Houston
Texas
Primary Children's Hospital
Salt Lake City
Utah
The Hospital for Sick Children
Toronto
Ontario
Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Shanghai
Shanghai Municipality
Beijing Children's Hospital, Capital Medical University
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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