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

Advanced Cancer Clinical Trial

Official title: Phase 1/2 Study of TPX-0005 (Repotrectinib) in Combination With Chemotherapy in Pediatric and Young Adult Subjects With Advanced or Metastatic Solid Tumors and Primary Central Nervous System Tumors

Status Recruiting

Clinical Trial Summary

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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Advanced Cancer
• Metastatic Solid Tumor
• Neoplasms

• NCT number: NCT05004116
• Study type: Interventional
• Source: Memorial Sloan Kettering Cancer Center
• Contact: Emily Slotkin, MD
• Phone: 1-833-675-5437
• Email: slotkine@mskcc.org
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: August 9, 2021
• Completion date: August 2028