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A Study of Repotrectinib in Pediatric and Young Adult Subjects Harboring ALK, ROS1, OR NTRK1-3 Alterations

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages N/A - 25 Years
Gender All
More Inclusion & Exclusion Criteria

Key

Inclusion Criteria:

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 50. 9. Life expectancy greater than or equal to 12 weeks. 10. Adequate hematologic, renal and hepatic function. Phase 2

Inclusion Criteria:

1. Age 12 to <25 years. 2. Cohort Specific

Inclusion Criteria:

  • - Cohort 1: Subjects with NTRK fusion gene positive (NTRK+) advanced solid tumors (including primary CNS tumors), that are tropomyosin receptor kinase (TRK) TKI naïve; - Cohort 2: subjects with NTRK+ advanced solid tumors (including primary CNS tumors), that are TRK TKI pre-treated; - 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.
3. Subjects in Cohorts 1 and 2 must have prospectively confirmed measurable disease by BICR prior to enrollment. Key Exclusion Criteria (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:
  • - 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.
  • - 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) - 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.
6. Peripheral neuropathy of CTCAE ≥grade 2. 7. Subjects being treated with or anticipating the need for treatment with strong CYP3A4 inhibitors or inducers.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT04094610
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1/Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Turning Point Therapeutics, Inc.
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Zachary Zimmerman, M.D.
Principal Investigator Affiliation Turning Point Therapeutics
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Industry
Overall Status Recruiting
Countries Australia, Canada, Korea, Republic of, Singapore, Taiwan, United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Locally Advanced Solid Tumors, Metastatic Solid Tumors, Lymphoma, Primary CNS Tumors
Additional 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.

Arms & Interventions

Arms

Experimental: Repotrectinib (TPX-0005)

Phase 1 Oral repotrectinib (TPX-0005): Safety and tolerability at different dose levels Phase 2 Oral repotrectinib (TPX-0005): 3 cohorts Cohort 1: TKI-naive NTRK fusion Cohort 2: Prior TKI NTRK fusion Cohort 3: ALK/ROS1/NTRK alterations or fusions in tumors and ALCL

Interventions

Drug: - Oral repotrectinib (TPX-0005)

Oral repotrectinib (TPX-0005)

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Children's Hospital Los Angeles, Los Angeles, California

Status

Recruiting

Address

Children's Hospital Los Angeles

Los Angeles, California, 90027

University of California, Los Angeles, Los Angeles, California

Status

Recruiting

Address

University of California, Los Angeles

Los Angeles, California, 90095

Children's Hospital Colorado, Aurora, Colorado

Status

Recruiting

Address

Children's Hospital Colorado

Aurora, Colorado, 80045

Arnold Palmer Hospital for Children, Orlando, Florida

Status

Recruiting

Address

Arnold Palmer Hospital for Children

Orlando, Florida, 32806

Maine Children's Cancer Program, Scarborough, Maine

Status

Recruiting

Address

Maine Children's Cancer Program

Scarborough, Maine, 04074

Dana-Farber Cancer Institute, Boston, Massachusetts

Status

Recruiting

Address

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215

Washington University School of Medicine, Saint Louis, Missouri

Status

Recruiting

Address

Washington University School of Medicine

Saint Louis, Missouri, 63110

Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey

Status

Recruiting

Address

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901

Memorial Sloan Kettering Cancer Center, New York, New York

Status

Recruiting

Address

Memorial Sloan Kettering Cancer Center

New York, New York, 10065

Cleveland Clinic, Cleveland, Ohio

Status

Recruiting

Address

Cleveland Clinic

Cleveland, Ohio, 44195

Hershey, Pennsylvania

Status

Recruiting

Address

Penn State Children's Hospital at Penn State Health Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033

Dallas, Texas

Status

Recruiting

Address

The University of Texas Southwestern Medical Center, Children's Medical Center of Dallas

Dallas, Texas, 75235

MD Anderson Cancer Center, Houston, Texas

Status

Recruiting

Address

MD Anderson Cancer Center

Houston, Texas, 77030

International Sites

Sydney Children's Hospital, Sydney, New South Wales, Australia

Status

Recruiting

Address

Sydney Children's Hospital

Sydney, New South Wales, 2031

The Children's Hospital at Westmead, Westmead, New South Wales, Australia

Status

Recruiting

Address

The Children's Hospital at Westmead

Westmead, New South Wales, 2145

Queensland Children's Hospital, South Brisbane, Queensland, Australia

Status

Recruiting

Address

Queensland Children's Hospital

South Brisbane, Queensland, 4101

Perth Children's Hospital, Nedlands, Western Australia, Australia

Status

Recruiting

Address

Perth Children's Hospital

Nedlands, Western Australia, 6009

Stollery Children's Hospital, Edmonton, Alberta, Canada

Status

Recruiting

Address

Stollery Children's Hospital

Edmonton, Alberta, T6G 2B7

Seoul National University Hospital, Seoul, Korea, Republic of

Status

Recruiting

Address

Seoul National University Hospital

Seoul, , 03080

Seoul, Korea, Republic of

Status

Recruiting

Address

Yonsei University Health System, Severance Hospital

Seoul, , 03722

Asan Medical Center, Seoul, Korea, Republic of

Status

Recruiting

Address

Asan Medical Center

Seoul, , 05505

Samsung Medical Center, Seoul, Korea, Republic of

Status

Recruiting

Address

Samsung Medical Center

Seoul, , 06351

National University Hospital, Singapore, Singapore

Status

Recruiting

Address

National University Hospital

Singapore, , 119074

KK Women's and Children's Hospital, Singapore, Singapore

Status

Recruiting

Address

KK Women's and Children's Hospital

Singapore, , 229899

National Taiwan University Hospital, Taipei City, Taiwan

Status

Recruiting

Address

National Taiwan University Hospital

Taipei City, , 100225

Taipei Medical University Hospital, Taipei, Taiwan

Status

Recruiting

Address

Taipei Medical University Hospital

Taipei, , 11031