A Study of Repotrectinib in Combination with Chemotherapy in Children and Young Adults with Solid Tumor Cancer

Sponsor: Memorial Sloan Kettering Cancer Center

Sponsor score: 60
Inactive

ClinicalTrials ID:NCT05004116

Patient View

This study evaluates the safety and efficacy of repotrectinib with chemotherapy in young patients with solid tumors. It involves dose escalation and pharmacokinetic analysis, with specific cohorts for neuroblastoma and other tumors. Exclusions include bone marrow disease, major recent surgery, and certain medical conditions. Repotrectinib is administered orally alongside irinotecan and temozolomide.

Patient Parameters

Program Overview

This study will test the safety of the study drug, repotrectinib, in combination with chemotherapy (irinotecan and temozolomide) in children and young adults who have advanced or metastatic solid tumors. We researchers will try to find the highest dose of the study drug that causes few or mild side effects in study participants. When the researchers find this dose, we will evaluate it in a different group of participants to find out whether repotrectinib in combination with chemotherapy is an effective treatment for children and young adults who have advanced/metastatic solid tumors. Another purpose of the study is to look at the way the body absorbs, distributes, and gets rid of repotrectinib.

Description

Part A : TPX-0005 (Repotrectinib) will be given orally (without regard to food) once daily for 14 days, then increased to twice daily for remainder of cycles and concurrently administered with chemotherapy backbone described below. If a patient is enrolled on DL3, cycle length will be 21 days, repotrectinib will be administered once daily x 14 days followed by twice daily if tolerated for remainder of therapy. For patients less than 12 years old or less than 50kg, adult equivalent dosing (AED) will be used Approximately 4-24 pediatric subjects will be enrolled into 2-4 dose levels (pending if DL-1 or DL-1b are utilized), with maximum of 6 subjects per dose level according to the 'rolling 6' design. Starting dose of TPX-0005 (Repotrectinib) will begin at dose level (DL) 1.

Part B (PK expansion cohort for patients <12 years old): Up to six patients <12 years old will be included in a PK expansion cohort after the maximum tolerated dose in Part A has been determined. The number of patients included in part B will be based on the the number of patients <12 years old enrolled on part A. A minimum of 6 patients <12 will be included in parts A and B combined.

Phase 2: Patients will be enrolled into one of the following 3 cohorts and will be treated at the RP2D of TPX-0005 (Repotrectinib) plus chemotherapy as determined in Phase 1.

Cohort 1 (Neuroblastoma ALK point mutation) Cohort 2 (Desmoplastic Small Round Cell Tumor) Cohort 3 (Exploratory)

Of note for patients enrolled to Dose Level 3 (21 day cycles), there will be no D22 assessements performed.

Eligibility Criteria

Exclusion Criteria

  • Phase 1- patients with known bone marrow disease
  • Concurrent participation in another therapeutic clinical trial
  • Neuroblastoma patients with only bone marrow disease evaluable only by bone marrow aspiration
  • Major surgery within 14 days (2 weeks) prior to C1D1. Central venous access (Broviac, MediPort) placement does not meet criteria for major surgery.
  • Pregnancy or lactation
  • Known active systemic infections requiring ongoing treatment (bacterial, fungal, viral including human immunodeficiency virus positivity). Skin or other superficial infections requiring topical treatment only are not an exclusion.
  • Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, short gut syndrome) or other malabsorption syndromes that would impact on drug absorption.
  • Peripheral neuropathy CTCAE grade ≥ 3.
  • Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or that may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the subject inappropriate for entry into this study, or could compromise protocol objectives in the opinion of the Investigator and/or Turning Point Therapeutics.
  • Current use or anticipated need for drugs that are known to be strong CYP3A4 inhibitors or inducers
  • Disease progression while on treatment with irinotecan/temozolomide.
  • Gilbert Syndrome or Crigler-Najjar
  • Prolonged QTc: 450m/s for male patients and 470ms for female patients.

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