We are experiencing 4 week turn-around time in review of submissions and resubmissions. We recommend commencing this process concurrently with your ethics submission and allowing at least 8 weeks for registration to be completed from date of first submission. We currently do not have the capacity to expedite reviews.

Note also there are delays to review of updates. We appreciate your patience.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

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




Registration number
NCT04094610
Ethics application status
Date submitted
12/09/2019
Date registered
19/09/2019
Date last updated
20/01/2021

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
TPX-0005-07
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
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: ALK/ROS1/NTRK alterations or fusions in tumors and ALCL


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) - Define the 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) - To determine the pediatric 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) - To determine the confirmed ORR of repotrectinib (TPX-0005) as assessed by Blinded Independent Central Review (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) - To determine the overall response rate (ORR) by Blinded Independent Central Review (BICR) (Phase 1)
Timepoint [1] 0 0
Approximately three years
Secondary outcome [2] 0 0
Clinical Benefit Rate (CBR) (Phase 1 and Phase 2) - To determine the CBR of repotrectinib (TPX-0005) (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) - To determine the TTR of reprotrectinib (TPX-005) (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) - To determine the DOR of repotrectinib (TPX-0005) (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) - To determine the IC-ORR of repotrectinib (TPX-005) (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) - CNS-PFS in subjects with measurable brain metastases (Phase 2)
Timepoint [6] 0 0
Approximately three years
Secondary outcome [7] 0 0
Progression-free survival (PFS) (Phase 2) - To determine the PFS (Phase 2)
Timepoint [7] 0 0
Approximately three years
Secondary outcome [8] 0 0
Overall survival (OS) (Phase 2) - To determine the OS (Phase 2)
Timepoint [8] 0 0
Approximately three years
Secondary outcome [9] 0 0
Maximum concentration of repotrectinib in plasma (Cmax) - To determine the 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) - To determine the 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 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

1. Age 12 to <25 years

2. 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 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
Minimum age
No limit
Maximum age
25 Years
Gender
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 (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.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
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/Phase 2
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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA
Recruitment hospital [1] 0 0
Sydney Children's Hospital - Sydney
Recruitment hospital [2] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [3] 0 0
Queensland Children's Hospital - South Brisbane
Recruitment hospital [4] 0 0
Perth Children's Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
2031 - Sydney
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
4101 - South Brisbane
Recruitment postcode(s) [4] 0 0
6009 - Nedlands
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
Texas
Country [12] 0 0
Canada
State/province [12] 0 0
Alberta
Country [13] 0 0
Korea, Republic of
State/province [13] 0 0
Seoul
Country [14] 0 0
Singapore
State/province [14] 0 0
Singapore
Country [15] 0 0
Taiwan
State/province [15] 0 0
Taipei City
Country [16] 0 0
Taiwan
State/province [16] 0 0
Taipei

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

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/show/NCT04094610
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Zachary Zimmerman, M.D.
Address 0 0
Turning Point Therapeutics
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Zachary Zimmerman, M.D.
Address 0 0
Country 0 0
Phone 0 0
(858) 276-0005
Fax 0 0
Email 0 0
clinical@tptherapeutics.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04094610