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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04094610




Registration number
NCT04094610
Ethics application status
Date submitted
12/09/2019
Date registered
19/09/2019

Titles & IDs
Public title
A Study of Repotrectinib in Pediatric and Young Adult Subjects Harboring ALK, ROS1, OR NTRK1-3 Alterations
Scientific 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
Secondary ID [1] 0 0
CA127-1029
Secondary ID [2] 0 0
CA127-1029
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Locally Advanced Solid Tumors 0 0
Metastatic Solid Tumors 0 0
Lymphoma 0 0
Primary CNS Tumors 0 0
Condition category
Condition code
Cancer 0 0 0 0
Brain
Cancer 0 0 0 0
Children's - Brain

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - Oral repotrectinib (TPX-0005)

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: ROS1 gene fusions or other ROS1 aberrations


Treatment: Drugs: Oral repotrectinib (TPX-0005)
Oral repotrectinib (TPX-0005)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Dose limiting toxicities (DLTs) (Phase 1)
Timepoint [1] 0 0
Within 28 days of the first repotrectinib dose
Primary outcome [2] 0 0
Pediatric Recommended Phase 2 Dose (RP2D) (Phase 1)
Timepoint [2] 0 0
Within 28 days of the last patient dosed in escalation
Primary outcome [3] 0 0
Overall Response Rate (ORR) (Phase 2)
Timepoint [3] 0 0
Two to three years after first dose of repotrectinib
Secondary outcome [1] 0 0
Overall Response Rate (ORR) (Phase 1)
Timepoint [1] 0 0
Approximately three years
Secondary outcome [2] 0 0
Clinical Benefit Rate (CBR) (Phase 1 and Phase 2)
Timepoint [2] 0 0
Approximately three years
Secondary outcome [3] 0 0
Time to response (TTR) (Phase 1 and Phase 2)
Timepoint [3] 0 0
Approximately three years
Secondary outcome [4] 0 0
Duration of response (DOR) (Phase 1 and Phase 2)
Timepoint [4] 0 0
Approximately three years
Secondary outcome [5] 0 0
Intracranial objective response rate (IC-ORR) (Phase 1 and Phase 2)
Timepoint [5] 0 0
Approximately three years
Secondary outcome [6] 0 0
Central Nervous System Progression-Free Survival (CNS-PFS) (Phase 2)
Timepoint [6] 0 0
Approximately three years
Secondary outcome [7] 0 0
Progression-free survival (PFS) (Phase 2)
Timepoint [7] 0 0
Approximately three years
Secondary outcome [8] 0 0
Overall survival (OS) (Phase 2)
Timepoint [8] 0 0
Approximately three years
Secondary outcome [9] 0 0
Maximum concentration of repotrectinib in plasma (Cmax)
Timepoint [9] 0 0
Pre-dose and up to 24 hours post-dose on Day 1 and Day 15 in Cycle 1 (each cycle is 28 days)
Secondary outcome [10] 0 0
Area under the concentration versus time curve of repotrectinib in plasma (AUC)
Timepoint [10] 0 0
Pre-dose and up to 24 hours post-dose on Day 1 and Day 15 in Cycle 1 (each cycle is 28 days)

Eligibility
Key inclusion criteria
Key

1. Documented genetic ROS1 point mutation, fusion, or amplification or NTRK1-3 fusion 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. Phase 1: Age <12 years; Phase 2: Age 12- 25 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 (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 7 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, in the investigator's opinion.
10. Adequate hematologic, renal and hepatic function.

Phase 2

1. Cohort Specific

* 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 advanced solid tumors with ROS1 gene fusions or other ROS1 aberrations (including amplifications and point mutations) with measurable disease.
2. Subjects in Cohorts 1 and 2 must have prospectively confirmed measurable disease by BICR prior to enrollment.

Key
Minimum age
No limit
Maximum age
25 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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 requiring ongoing treatment (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) > 480 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.
8. Any potential allergies to repotrectinib and/or its excipients.

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
12/03/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/09/2027
Actual
Sample size
Target
75
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA
Recruitment hospital [1] 0 0
Local Institution - 6104 - Randwick
Recruitment hospital [2] 0 0
Local Institution - 6103 - Westmead
Recruitment hospital [3] 0 0
Local Institution - 6102 - South Brisbane
Recruitment hospital [4] 0 0
Local Institution - 6101 - Perth
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
0 - Westmead
Recruitment postcode(s) [3] 0 0
4101 - South Brisbane
Recruitment postcode(s) [4] 0 0
6009 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Maine
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Missouri
Country [7] 0 0
United States of America
State/province [7] 0 0
New Jersey
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
Ohio
Country [10] 0 0
United States of America
State/province [10] 0 0
Pennsylvania
Country [11] 0 0
United States of America
State/province [11] 0 0
Tennessee
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
United States of America
State/province [13] 0 0
Virginia
Country [14] 0 0
Canada
State/province [14] 0 0
Alberta
Country [15] 0 0
Denmark
State/province [15] 0 0
Copenhagen
Country [16] 0 0
France
State/province [16] 0 0
Rhone
Country [17] 0 0
France
State/province [17] 0 0
Angers Cedex 1
Country [18] 0 0
France
State/province [18] 0 0
Bordeaux
Country [19] 0 0
France
State/province [19] 0 0
Marseille Cedex 5
Country [20] 0 0
France
State/province [20] 0 0
Nantes
Country [21] 0 0
France
State/province [21] 0 0
Paris
Country [22] 0 0
France
State/province [22] 0 0
Villejuif
Country [23] 0 0
Italy
State/province [23] 0 0
Milano
Country [24] 0 0
Italy
State/province [24] 0 0
Padova
Country [25] 0 0
Italy
State/province [25] 0 0
Rome
Country [26] 0 0
Italy
State/province [26] 0 0
Torino
Country [27] 0 0
Korea, Republic of
State/province [27] 0 0
Seodaemun-gu
Country [28] 0 0
Korea, Republic of
State/province [28] 0 0
Seoul
Country [29] 0 0
Singapore
State/province [29] 0 0
Singapore
Country [30] 0 0
Spain
State/province [30] 0 0
Boadilla Del Monte
Country [31] 0 0
Spain
State/province [31] 0 0
Navarra
Country [32] 0 0
Spain
State/province [32] 0 0
Barcelona
Country [33] 0 0
Spain
State/province [33] 0 0
Madrid
Country [34] 0 0
Spain
State/province [34] 0 0
Valencia
Country [35] 0 0
Taiwan
State/province [35] 0 0
Taipei
Country [36] 0 0
United Kingdom
State/province [36] 0 0
England
Country [37] 0 0
United Kingdom
State/province [37] 0 0
Birmingham
Country [38] 0 0
United Kingdom
State/province [38] 0 0
Cardiff
Country [39] 0 0
United Kingdom
State/province [39] 0 0
Glasgow
Country [40] 0 0
United Kingdom
State/province [40] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Turning Point Therapeutics, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bristol-Myers Squibb
Address 0 0
Bristol-Myers Squibb
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
BMS Study Connect Contact Center www.BMSStudyConnect.com
Address 0 0
Country 0 0
Phone 0 0
855-907-3286
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
There are no plans to share individual participant data with other researchers.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04094610