Larotrectinib for Childhood Cancer
(SCOUT Trial)

Recruiting in Palo Alto (17 mi)

+68 other locations

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Waitlist Available

Sponsor: Bayer

No Placebo Group

Breakthrough Therapy

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?The study is being done to test the safety of a cancer drug called larotrectinib in children. The cancer must have a change in a particular gene (NTRK1, NTRK2 or NTRK3). Larotrectinib blocks the actions of these NTRK genes in cancer cells and can therefore be used to treat cancer. The first study part (Phase 1) is done to determine what dose level of larotrectinib is safe for children, how the drug is absorbed and changed by their bodies and how well the cancer responds to the drug. The main purpose of the second study part (Phase 2) is to investigate how well and how long different cancer types respond to the treatment with larotrectininb.

Eligibility Criteria

This trial is for children and young adults up to age 21 with advanced or metastatic solid tumors, including CNS tumors that have not responded to other treatments. Eligible patients must have a specific gene change (NTRK fusion) in their cancer cells. Those with certain heart conditions, active infections, or recent major surgery are excluded.

Inclusion Criteria

Phase 1 (Closed): Patients birth through 21 years of age with a locally advanced or metastatic solid tumor or primary CNS tumor that has relapsed, progressed, or was nonresponsive to available therapies and for which no standard or available systemic curative therapy exists; OR Infants from birth and older with a diagnosis of malignancy and documented NTRK fusion that has progressed or was nonresponsive to available therapies, and for which no standard or available curative therapy exists; OR Patients with locally advanced infantile fibrosarcoma who would require, in the opinion of the investigator, disfiguring surgery or limb amputation to achieve a complete surgical resection. Phase I dose escalation cohorts are closed to enrollment. Dose expansion: In addition to the above stated inclusion criteria, patients must have a malignancy with a documented NTRK gene fusion with the exception of patients with infantile fibrosarcoma, congenital mesoblastic nephroma, or secretory breast cancer. Patients with infantile fibrosarcoma, congenital mesoblastic nephroma, or secretory breast cancer may enroll into this cohort with documentation of an ETV6 rearrangement by FISH or RT-PCR or a documented NTRK fusion by next generation sequencing. Phase 2: Infants from birth and older at C1D1 with a locally advanced or metastatic infantile fibrosarcoma, patients with locally advanced infantile fibrosarcoma who would require, in the opinion of the investigator, disfiguring surgery or limb amputation to achieve a complete surgical resection; OR Birth through 21 years of age at C1D1 with a locally advanced or metastatic solid tumor or primary CNS tumor that has relapsed, progressed, or was nonresponsive to available therapies and for which no standard or available systemic curative therapy exists with a documented NTRK gene fusion (or in the case of infantile fibrosarcoma, congenital mesoblastic nephroma, or secretory breast cancer with documented ETV6 rearrangement (or NTRK3 rearrangement after discussion with the sponsor) by FISH or RT-PCR. Patients with NTRK-fusion positive benign tumors are also eligible; OR Potential patients older than 21 years of age with a tumor diagnosis with histology typical of a pediatric patient and an NTRK fusion may be considered for enrollment following discussion between the local site Investigator and the Sponsor. Patients with primary CNS tumors or cerebral metastasis; Karnofsky (those 16 years and older) or Lansky (those younger than 16 years) performance score of at least 50; Adequate hematologic function; Adequate hepatic and renal function

Exclusion Criteria

Major surgery within 14 days (2 weeks) prior to C1D1; Clinically significant active cardiovascular disease or history of myocardial infarction within 6 months prior to C1D1, ongoing cardiomyopathy; current prolonged QTc interval > 480 milliseconds; Active uncontrolled systemic bacterial, viral, or fungal infection; Current treatment with a strong CYP3A4 inhibitor or inducer. Enzyme-inducing anti-epileptic drugs (EIAEDs) and dexamethasone for CNS tumors or metastases, on a stable dose, are allowed. Phase 2 only: Prior progression while receiving approved or investigational tyrosine kinase inhibitors targeting TRK, including entrectinib, crizotinib, and lestaurtinib. Patients who received a TRK inhibitor for less than 28 days of treatment and discontinued because of intolerance remain eligible.

Participant Groups

The drug larotrectinib is being tested for safety and effectiveness in treating cancers with NTRK gene changes. The study has two parts: Phase 1 determines the safe dose for children and how they respond; Phase 2 examines the treatment's response duration across different cancer types.

6Treatment groups

Experimental Treatment

Group I: Phase 2: Primary CNS tumors_Cohort 3Experimental Treatment1 Intervention

Patients will receive larotrectinib dose on Day 1 (BID in accordance with the cohort assignment) at the recommended Phase 2 dose as determined in the Phase 1 portion of this study. Each cycle will consist of 28 days of continuous dosing. Individual patients will continue daily larotrectinib dosing until PD, unacceptable toxicity, or other reason for treatment discontinuation.

Group II: Phase 2: Patients with tumors bearing NTRK fusions (IFS)_Cohort 1Experimental Treatment1 Intervention

Group III: Phase 2: Other extra-cranial solid tumors_Cohort 2Experimental Treatment1 Intervention

Group IV: Phase 2: Bone health assessment_sub-cohortExperimental Treatment1 Intervention

Group V: Phase 1 dose expansionExperimental Treatment1 Intervention

Patients who are enrolled in the expansion cohort, following the formal dose escalation phase of the study. Distinct from the Phase 1 dose escalation cohort, the Phase 1 expansion cohort will enroll pediatric patients with advanced solid or primary CNS tumors with a documented NTRK gene fusion, or in the case of IFS, CMN or SBC with documented ETV6 rearrangement by FISH or RT-PCR or a documented NTRK fusion by NGS. This expansion cohort will follow the same schedule of assessments as the dose escalation cohorts. (arm closed)

Group VI: Phase 1 dose escalationExperimental Treatment1 Intervention

Patients will receive the different levels of dose on Day 1 (BID in accordance with the cohort assignment). Each cycle will consist of 28 days of continuous dosing. Individual patients will continue daily larotrectinib dosing until PD, unacceptable toxicity, or other reason for treatment discontinuation. (arm closed)

Larotrectinib is already approved in United States, European Union, Australia for the following indications:

🇺🇸 Approved in United States as Vitrakvi for: