Summary

Eligibility
for people ages up to 25 years (full criteria)
Location
at UCLA
Dates
study started
estimated completion
Principal Investigator
by Noah Federman (ucla)

Description

Summary

Phase 1 will evaluate the safety and tolerability at different dose levels of repotrectinib in pediatric and young adult subjects with advanced or metastatic malignancies harboring anaplastic lymphoma kinase (ALK), receptor tyrosine kinase encoded by the gene ROS1 (ROS1), or neurotrophic receptor kinase genes encoding TRK kinase family (NTRK1-3) alterations to estimate the Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) and select the Pediatric Recommended Phase 2 Dose (RP2D). Phase 2 will determine the anti-tumor activity of repotrectinib in pediatric subjects with advanced or metastatic malignancies harboring ALK, ROS1, or NTRK1-3 alterations.

Official Title

A Phase 1/2, Open-Label, Safety, Tolerability, Pharmacokinetics, and Anti-Tumor Activity Study of Repotrectinib in Pediatric and Young Adult Subjects With Advanced or Metastatic Malignancies Harboring ALK, ROS1, NTRK1-3 Alterations

Details

Enrollment of subjects into Phase 1 will proceed concurrently by age as follows: - Subjects <12 years old will initially be enrolled in the Phase 1 part to determine the pediatric RP2D for this age group; once the pediatric RP2D is determined, subjects age <12 years old may be enrolled into the Phase 2 part of the study. - Subjects 12 to 25 years old will be directly enrolled into the Phase 2 part concurrent with Phase 1 enrollment. Phase 1: Approximately 12 pediatric subjects with locally advanced or metastatic solid tumors, including a primary central nervous system (CNS) tumor, or anaplastic large cell lymphoma (ALCL), with disease progression or who are non-responsive or intolerant to available therapies and for which no standard or available curative therapy exists. Phase 2: Subjects will be enrolled in one of 3 cohorts as follows: Cohort 1: approximately 10-20 subjects with solid tumors characterized by NTRK fusion, TRK tyrosine kinase inhibitor (TKI)-naïve, and centrally confirmed measurable disease at baseline. Cohort 2: approximately 23 subjects with solid tumors characterized by NTRK fusion, TRK TKI-pretreated, and centrally confirmed measurable disease at baseline. Cohort 3: approximately 20 subjects with solid tumors or ALCL characterized by other ALK/ROS1/NTRK alterations or NTRK fusions without centrally confirmed measurable disease not otherwise eligible for Cohort 1 or 2.

Keywords

Locally Advanced Solid Tumors Metastatic Solid Tumors Lymphoma Primary CNS Tumors ALK ROS1 NTRK1-3 Primary CNS tumor anaplastic large cell lymphoma metastatic solid tumor advanced solid tumor sarcoma infantile fibrosarcoma glioblastoma soft tissue schwannoma solitary fibrous tumor glioma inflammatory myofibroblastic tumor pediatric Neoplasms Central Nervous System Neoplasms Oral repotrectinib (TPX-0005) Repotrectinib (TPX-0005)

Eligibility

You can join if…

Open to people ages up to 25 years

  1. Documented genetic ALK, ROS1, or NTRK1-3 alteration (point mutation, fusion, amplification) as identified by local testing in a Clinical Laboratory Improvement Amendments (CLIA) laboratory in the US or equivalently accredited diagnostic lab outside the United States (US) is required.
  2. Age <12 years.
  3. Prior cytotoxic chemotherapy is allowed.
  4. Prior immunotherapy is allowed.
  5. Resolution of all acute toxic effects (excluding alopecia) of any prior anti-cancer therapy to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Grade less than or equal to 1.
  6. All subjects must have measurable disease by RECIST v1.1 or Response Assessment in Neuro-Oncology Criteria (RANO) criteria at time of enrollment.
  7. Subjects with a primary CNS tumor or CNS metastases must be neurologically stable on a stable or decreasing dose of steroids for at least 14 days prior to enrollment.
  8. Subjects must have a Lansky (< 16 years) or Karnofsky (≥ 16 years) score of at least
  9. .
  10. Life expectancy greater than or equal to 12 weeks.
  11. . Adequate hematologic, renal and hepatic function.

Phase 2 Inclusion Criteria:

  1. Age 12 to <25 years
  2. Cohort Specific Inclusion Criteria:
  3. Cohort 1: Subjects with NTRK fusion gene positive (NTRK+) advanced solid tumors (including primary CNS tumors), that are tropomyosin receptor kinase (TRK) TKI naïve;
  4. Cohort 2: subjects with NTRK+ advanced solid tumors (including primary CNS tumors), that are TRK TKI pre-treated;
  5. Cohort 3: subjects with tumors or ALCL characterized by other ALK/ROS1/NTRK alterations or NTRK fusions without centrally confirmed measurable disease or not otherwise eligible for Cohort 1 or 2.
  6. Subjects in Cohorts 1 and 2 must have prospectively confirmed measurable disease by BICR prior to enrollment.

You CAN'T join if...

(Phase 1 and Phase 2):

  1. Subjects with neuroblastoma with only bone marrow disease evaluable by bone marrow aspiration only.
  2. Major surgery within 14 days (2 weeks) of start of repotrectinib treatment. Central venous access (Broviac, Mediport, etc.) placement does not meet criteria for major surgery.
  3. Known active infections (bacterial, fungal, viral including HIV positivity).
  4. Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would impact drug absorption.
  5. Any of the following cardiac criteria:
  6. Mean resting corrected QT interval (ECG interval measured from the onset of the QRS complex to the end of the T wave) for heart rate (QTc) > 470 msec obtained from three ECGs, using the screening clinic ECG machine-derived QTc value
  7. Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block, PR interval > 250 msec)
  8. Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, congenital long QT syndrome, family history of long QT syndrome, or any concomitant medication known to prolong the QT interval
  9. Peripheral neuropathy of CTCAE ≥grade 2.
  10. Subjects being treated with or anticipating the need for treatment with strong CYP3A4 inhibitors or inducers.

Locations

  • University of California, Los Angeles accepting new patients
    Los Angeles California 90095 United States
  • Children's Hospital Los Angeles accepting new patients
    Los Angeles California 90027 United States

Lead Scientist at UC Cancer

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Turning Point Therapeutics, Inc.
ID
NCT04094610
Phase
Phase 1/2
Study Type
Interventional
Last Updated