RECRUITING

A Study of Repotrectinib (TPX-0005) in Patients With Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 Rearrangements

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Conditions

Locally Advanced Solid TumorsMetastatic Solid TumorsALKROS1NTRKSarcomaLung NeoplasmsCarcinoma, NSCLNSCLCNon Small Cell LungThyroid DiseaseColonic NeoplasmsThyroid NeoplasmsCarcinoma, NeuroendocrineRespiratory Tract NeoplasmsThoracic NeoplasmsNeoplasms by SiteNeoplasmsLung DiseaseRespiratory Tract DiseaseCarcinoma, BronchogenicBronchial NeoplasmsEndocrine System DiseaseColorectol NeoplasmsIntestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsGastrointestinal DiseaseColonic DiseaseIntestinal DiseaseEndocrine Gland NeoplasmsHead and Neck NeoplasmsNeuroendocrine TumorsNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeAdenocarcinomaNon Small Cell Lung CancerSolid TumorsRearrangementsTRIDENT-1TKITKI naiveTKI pretreatedAnti-tumor activityRepotrectinibAdvanced Solid Malignancies

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

Phase 1 dose escalation will determine the first cycle dose-limiting toxicities (DLTs), the maximum tolerated dose (MTD), the biologically effective dose and recommended Phase 2 dose (RP2D) of repotrectinib given to adult subjects with advanced solid malignancies harboring an ALK, ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement. Midazolam DDI substudy will examine effect of of repotrectinib on CYP3A induction. Phase 2 will determine the confirmed Overall Response Rate (ORR) as assessed by Blinded Independent Central Review (BICR) of repotrectinib in each subject population expansion cohort of advanced solid tumors that harbor a ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement. The secondary objective will include the duration of response (DOR), time to response (TTR), progression-free survival (PFS), overall survival (OS) and clinical benefit rate (CBR) of repotrectinib in each expansion cohort of advanced solid tumors that harbor a ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement.

Official Title

A Phase 1/2, Open-Label, Multi-Center, First-in-Human Study of the Safety, Tolerability, Pharmacokinetics, and Anti-Tumor Activity of TPX-0005 in Patients With Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 Rearrangements (TRIDENT-1)

Quick Facts

Study Start:2017-03-07
Study Completion:2028-02-29
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT03093116

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:12 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:CHILD, ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. 1. Histologically or cytologically confirmed diagnosis of locally advanced, or metastatic solid tumor (including primary CNS tumors) (Stage IV, American Joint Committee on Cancer v.7) that harbors an ALK, ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement by protocol specified tests.
  2. 2. ECOG PS 0-1.
  3. 3. Age ≥18 (or age ≥ 20 of age as required by local regulation).
  4. 4. Capability to swallow capsules intact (without chewing, crushing, or opening).
  5. 5. At least 1 measurable target lesion according to RECIST version 1.1. CNS-only measurable disease as defined by RECIST version 1.1 is allowed.
  6. 6. Prior cytotoxic chemotherapy is allowed.
  7. 7. Prior immunotherapy is allowed.
  8. 8. 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.
  9. 9. Patients with asymptomatic CNS metastases (treated or untreated) and/or asymptomatic leptomeningeal carcinomatosis are eligible to enroll if they satisfy the protocol specified criteria.
  10. 10. Baseline laboratory values fulfilling the following requirements:Absolute neutrophils count (ANC) ≥1500/mm3 (1.5 × 109/L); Platelets (PLTs) ≥100,000/mm3 (100 × 109/L); Hemoglobin ≥ 9.0 g/dL transfusions are allowed; Serum creatinine or creatinine clearance Within normal limits or \> 40 mL/min; Total serum bilirubin \< 1.5 × ULN; Liver transaminases (ASTs/ALTs) \< 2.5 × ULN; \< 5 × ULN if liver metastases are present Alkaline phosphatase (ALP); \< 2.5 × ULN; \< 5 × ULN if liver and/or bone metastasis are present; Serum calcium, magnesium, and potassium Normal or CTCAE grade ≤ 1 with or without supplementation
  11. 11. Life expectancy ≥ 3 months.
  12. 1. Histologically or cytologically confirmed diagnosis of locally advanced, or metastatic solid tumor (including primary CNS tumors) that harbors a ROS1, or NTRK1-3 gene fusion.
  13. 2. Subject must have a documented ROS1 or NTRK1-3 gene fusion determined by tissue-based local testing using either:
  14. 1. a next-generation sequencing (NGS) or quantitative polymerase chain reaction (qPCR) test will be accepted to determine molecular eligibility.
  15. 2. a fluorescence in situ hybridization (FISH) test AND prospective confirmation of fusion status by a central diagnostic laboratory test selected by the Sponsor PRIOR to enrollment will be accepted to determine molecular eligibility.
  16. * Adequate tumor tissue must be sent to the Sponsor designated central diagnostic laboratory for prospective confirmation by a central diagnostic laboratory test selected by the Sponsor PRIOR to enrollment.
  17. 3. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
  18. 4. Age ≥12 (or age ≥ 20 as required by local regulation).
  19. 5. Willing and able to provide written institutional review board (IRB)/institutional ethics committee-approved Informed Consent or an Assent signed by a parent or legal guardian for subjects age 12 to 17.
  20. 6. At least 1 measurable target lesion according to RECIST (v1.1) prospectively confirmed by Blinded Independent Central Radiology Review (BICR), selected by Sponsor, PRIOR to enrollment. Subjects with CNS-only measurable disease ≥10 mm as defined by RECIST (v1.1) are eligible.
  21. 7. Subjects with advanced solid tumors harboring ROS1, NTRK1, NTRK2, or NTRK3 rearrangement will be assigned into 6 distinct expansion (EXP) cohorts provided all inclusion and exclusion criteria are met.
  22. 8. Subjects with asymptomatic CNS metastases (treated or untreated) and/or asymptomatic leptomeningeal carcinomatosis are eligible to enroll if they satisfy the protocol specified criteria.
  23. 9. Baseline laboratory values fulfilling the following requirements:Absolute neutrophils count (ANC) ≥1500/mm3 (1.5 × 109/L); Platelets (PLTs) ≥100,000/mm3 (100 × 109/L); Hemoglobin ≥ 9.0 g/dL transfusions are allowed; Serum creatinine or creatinine clearance \> 40 mL/min; Total serum bilirubin \< 1.5 × ULN; Liver transaminases (ASTs/ALTs) \< 2.5 × ULN; \< 5 × ULN if liver metastases are present Alkaline phosphatase (ALP); \< 2.5 × ULN; \< 5 × ULN if liver and/or bone metastasis are present; Serum calcium, magnesium, and potassium Normal or CTCAE grade ≤ 1 with or without supplementation
  24. 10. Life expectancy ≥ 3 months.
  25. 1. Concurrent participation in another therapeutic clinical trial.
  26. 2. Symptomatic brain metastases or leptomeningeal involvement.
  27. 3. History of previous cancer, except for squamous cell or basal-cell carcinoma of the skin, or any in situ carcinoma that has been completely resected, requiring therapy within the previous 2 years.
  28. 4. Major surgery within 4 weeks of start of repotrectinib treatment. Radiation therapy (except palliative to relieve bone pain) within 2 weeks of study entry. Palliative radiation (≤10 fractions) must have been completed at least 48 hours prior to study entry
  29. 5. Clinically significant cardiovascular disease (either active or within 6 months prior to enrollment): myocardial infarction, unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (New York Heart Association Classification Class ≥ II), cerebrovascular accident or transient ischemic attack, symptomatic bradycardia, requirement for anti-arrhythmic medication. Ongoing cardiac dysrhythmias of NCI CTCAE grade ≥2
  30. 6. Any of the following cardiac criteria:
  31. 7. Known active infections (bacterial, fungal, viral including HIV positivity).
  32. 8. Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would impact drug absorption.
  33. 9. Peripheral neuropathy of CTCAE ≥grade 2.
  34. 10. History of extensive, disseminated, bilateral, or presence of CTCAE grade 3 or 4 interstitial fibrosis or interstitial lung disease including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis, and pulmonary fibrosis. Subjects with history of prior radiation pneumonitis are not excluded.
  1. Pregnancy or breastfeeding
  2. Severe psychiatric disorders
  3. Active substance abuse
  4. Unstable medical conditions
  5. Inability to comply with study requirements

Contacts and Locations

Study Contact

BMS Study Connect Contact Center www.BMSStudyConnect.com
CONTACT
855-907-3286
Clinical.Trials@bms.com
First line of the email MUST contain the NCT# and Site #.
CONTACT

Principal Investigator

Bristol-Myers Squibb
STUDY_DIRECTOR
Bristol-Myers Squibb

Study Locations (Sites)

City Of Hope
Duarte, California, 91010
United States
Adventist Health Glendale
Glendale, California, 91206
United States
UC San Diego Health
La Jolla, California, 92093
United States
Pacific Shores Medical Group
Long Beach, California, 90813
United States
Local Institution - 1001
Orange, California, 92868
United States
UC Irvine Medical Center
Orange, California, 92868
United States
St Joseph Heritage Healthcare
Santa Rosa, California, 95403
United States
Local Institution - 1003
Aurora, Colorado, 80045
United States
University Of Colorado Denver
Aurora, Colorado, 80045
United States
Georgetown University Medical Center - Lombardi Comprehensive Cancer Center
Washington, District of Columbia, 20007
United States
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Washington, District of Columbia, 20016
United States
Memorial Healthcare System
Hollywood, Florida, 33021
United States
Moffitt Cancer Center
Tampa, Florida, 33612
United States
University Cancer and Blood Center
Athens, Georgia, 30607
United States
Colombus Regional Research Institute
Columbus, Georgia, 31904
United States
University of Chicago
Chicago, Illinois, 60637
United States
Illinois Cancer Care
Peoria, Illinois, 61615
United States
University of Maryland Medical Center
Baltimore, Maryland, 21210
United States
Massachusetts General Hospital,
Boston, Massachusetts, 02114
United States
Local Institution - 1004
Boston, Massachusetts, 02214
United States
Dana Farber Cancer Institute.
Boston, Massachusetts, 02215
United States
University Of Michigan
Ann Arbor, Michigan, 48109
United States
Karmanos Cancer Institute
Detroit, Michigan, 48201
United States
Henry Ford Transplant Institute
Detroit, Michigan, 48202-2608
United States
Regions Hospital - Cancer Care Center
Saint Paul, Minnesota, 55101
United States
Central Care Cancer Center
Bolivar, Missouri, 65613
United States
Washington University Infusion Center Pharmacy
Saint Louis, Missouri, 63110
United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08901
United States
Laura & Isaac Perlmutter Cancer Center
New York, New York, 10016
United States
Local Institution - 1002
New York, New York, 10065
United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
United States
Southeastern Medical Oncology Center
Goldsboro, North Carolina, 27534
United States
Gabrail Cancer Center
Canton, Ohio, 44718
United States
Trihealth Cancer Institute
Cincinnati, Ohio, 45220
United States
Cleveland Clinic Main Campus
Cleveland, Ohio, 44195
United States
The Ohio State University Wexner Medical Center
Columbus, Ohio, 43210
United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111-2497
United States
Baptist Memorial Hospital Baptist Cancer Center
Memphis, Tennessee, 38120
United States
UT Southwestern Medical Center
Dallas, Texas, 75390
United States
MD Anderson Cancer Center
Houston, Texas, 77030
United States
Oncology Consultants, P.A.
Houston, Texas, 77030
United States
Lumi Research
Kingwood, Texas, 77339
United States
Virginia Cancer Specialists, PC
Fairfax, Virginia, 22031
United States
University of Washington-Seattle Cancer Care Alliance
Seattle, Washington, 98109
United States
ThedaCare
Appleton, Wisconsin, 54911
United States

Collaborators and Investigators

Sponsor: Turning Point Therapeutics, Inc.

  • Bristol-Myers Squibb, STUDY_DIRECTOR, Bristol-Myers Squibb

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2017-03-07
Study Completion Date2028-02-29

Study Record Updates

Study Start Date2017-03-07
Study Completion Date2028-02-29

Terms related to this study

Keywords Provided by Researchers

  • ALK
  • ROS1
  • NTRK
  • Sarcoma
  • Lung Neoplasms
  • Carcinoma, NSCL
  • NSCLC
  • Non Small Cell Lung
  • Thyroid Disease
  • Colonic Neoplasms
  • Thyroid Neoplasms
  • Carcinoma, Neuroendocrine
  • Respiratory Tract Neoplasms
  • Thoracic Neoplasms
  • Neoplasms by Site
  • Neoplasms
  • Lung Disease
  • Respiratory Tract Disease
  • Carcinoma, Bronchogenic
  • Bronchial Neoplasms
  • Endocrine System Disease
  • Colorectol Neoplasms
  • Intestinal Neoplasms
  • Gastrointestinal Neoplasms
  • Digestive System Neoplasms
  • Gastrointestinal Disease
  • Colonic Disease
  • Intestinal Disease
  • Endocrine Gland Neoplasms
  • Head and Neck Neoplasms
  • Neuroendocrine Tumors
  • Neuroectodermal Tumors
  • Neoplasms, Germ Cell and Embryonal
  • Neoplasms by Histologic Type
  • Adenocarcinoma
  • Non Small Cell Lung Cancer
  • Solid Tumors
  • Rearrangements
  • TRIDENT-1
  • TKI
  • TKI naive
  • TKI pretreated
  • Anti-tumor activity
  • Repotrectinib
  • Advanced Solid Malignancies

Additional Relevant MeSH Terms

  • Locally Advanced Solid Tumors
  • Metastatic Solid Tumors