What side effects are associated with this type of intervention?

Tyrosine kinase inhibitors (TKIs) like repotrectinib commonly cause side effects such as diarrhea, skin toxicity (rash or erythema), and fatigue. Chemotherapy agents, often used in combination with TKIs, can lead to a range of side effects including nausea, vomiting, hair loss, and myelosuppression (reduced bone marrow activity leading to fewer blood cells). Specific combinations, such as irinotecan and temozolomide, may also cause gastrointestinal disturbances and increased risk of infection due to immunosuppression.

What prior FDA approvals exist?

Several tyrosine kinase inhibitors (TKIs) have received FDA approval for the treatment of various cancers. Examples include imatinib (Gleevec) for chronic myeloid leukemia (CML) and gastrointestinal stromal tumors (GIST), erlotinib (Tarceva) for non-small cell lung cancer (NSCLC) and pancreatic cancer, and sunitinib (Sutent) for renal cell carcinoma (RCC) and GIST. These drugs work by targeting specific tyrosine kinases involved in cancer cell proliferation and survival. Repotrectinib, being studied for advanced or metastatic solid tumors, is part of this class of targeted therapies aimed at inhibiting cancer growth by blocking tyrosine kinase activity.

What other types of research exist?

Promising alternatives to Repotrectinib for cancer treatment include Larotrectinib and Entrectinib, which are both TKIs showing potential advantages in clinical response and survival for TRK fusion cancers. Additionally, Selpercatinib, another TKI, has shown efficacy in RET fusion-positive solid tumors. These alternatives are supported by recent clinical trials and data.

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Topoisomerase I inhibitor and Alkylating agent

Repotrectinib + Chemotherapy for Cancer

Phase 1 & 2

Recruiting

Led By Emily Slotkin, MD

Research Sponsored by Memorial Sloan Kettering Cancer Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients must have fully recovered from the acute toxic effects of all previous chemotherapy, immunotherapy, or radiotherapy prior to study enrollment

Patients with primary CNS tumors must meet specific neurological stability and performance score criteria

Must not have

Disease progression while on treatment with irinotecan/temozolomide

Neuroblastoma patients with only bone marrow disease evaluable only by bone marrow aspiration

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 1 year

Awards & highlights

No Placebo-Only Group

Summary

This trial tests the safety and effectiveness of repotrectinib combined with chemotherapy in children and young adults with severe, spreading cancer. The goal is to find the best dose with few side effects and see if it works well to stop cancer growth.

Who is the study for?

This trial is for children and young adults with advanced or metastatic solid tumors who have not responded to standard therapy. They must have a certain level of physical ability, no severe infections, and meet specific blood count and organ function criteria. Pregnant individuals or those on strong CYP3A4 inhibitors are excluded.

What is being tested?

Researchers are testing the safety of repotrectinib combined with chemotherapy drugs irinotecan and temozolomide. The goal is to find the highest dose with minimal side effects, then see if it's effective against these types of cancers in youths.

What are the potential side effects?

Possible side effects include reactions related to drug infusion, digestive issues that might affect how the drug works, nerve pain (neuropathy), blood disorders from bone marrow involvement, liver problems like jaundice or hepatitis, heart issues such as abnormal rhythms.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have recovered from side effects of my previous cancer treatments.

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My brain tumor does not affect my daily activities much.

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My cancer can be measured or seen on tests.

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My condition did not improve after standard treatment.

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My blood counts and organ functions meet the required levels.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My condition worsened while I was being treated with irinotecan/temozolomide.

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My neuroblastoma is only in my bone marrow and confirmed by a specific test.

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I am currently being treated for an active infection.

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I have a known bone marrow disease.

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I have a stomach or intestine condition that affects how drugs are absorbed.

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I am using or might need strong CYP3A4 affecting drugs.

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I have not had major surgery in the last 2 weeks.

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My heart's electrical cycle is within normal range for my gender.

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I have Gilbert Syndrome or Crigler-Najjar.

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I have severe nerve pain or numbness.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 1 year

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~1 year

This trial's timeline: 3 weeks for screening, Varies for treatment, and 1 year for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Maximum tolerated dose (MTD) (phase I)

incidence of Dose Limiting Toxicity (DLTs) (phase I)

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

5Treatment groups

Experimental Treatment

Group I: Phase II, Molecularly defined DSRCT CohortExperimental Treatment2 Interventions

Phase II, Molecularly defined DSRCT Cohort. Participants will be treated with the recommended phase 2 dose of TPX-0005 (Repotrectinib) + chemotherapy determined in Phase 1

Group II: Phase II, Exploratory CohortExperimental Treatment2 Interventions

Phase II, Exploratory Cohort. Participants will be treated with the recommended phase 2 dose of TPX-0005 (Repotrectinib) + chemotherapy determined in Phase 1

Group III: Phase II, DIPG CohortExperimental Treatment2 Interventions

Patients with DIPG will enroll in cohort 4 and receive TPX-0005 (Repotrectinib) monotherapy at the pediatric recommended phase 2 dose

Group IV: Phase II, ALK-mutated neuroblastoma CohortExperimental Treatment2 Interventions

Phase II, ALK-mutated neuroblastoma Cohort. Participants will be treated with the recommended phase 2 dose of TPX-0005 (Repotrectinib) + chemotherapy determined in Phase 1

Group V: Phase I portionExperimental Treatment2 Interventions

Phase 1: 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. 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 (combination therapy; patients less than 12 years old or ≤ 50kg): For 6 additional patients, a safety run-in will be conducted with TPX-0005 (Repotrectinib) and chemotherapy.

0 / 15Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Tyrosine Kinase Inhibitors (TKIs) like Repotrectinib work by targeting specific enzymes involved in cell signaling pathways that control cell growth and survival. By inhibiting these enzymes, TKIs can effectively block the proliferation and spread of cancer cells. This targeted approach is crucial for cancer patients as it can lead to more effective treatments with fewer side effects compared to traditional chemotherapy, which indiscriminately affects both healthy and cancerous cells. Moreover, the specificity of TKIs allows for personalized treatment plans, enhancing the overall efficacy and minimizing unnecessary toxicity.

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