Larotrectinib for TRK Fusion Cancers and Acute Leukemia

Recruiting at 92 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Children's Oncology Group

Must not be taking: CYP3A4 inducers, CYP3A4 inhibitors

Disqualifiers: Pregnancy, Breastfeeding, High grade gliomas, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 24 months

31 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of the drug larotrectinib (also known as Vitrakvi, LOXO-101, or ARRY-470) on cancers with TRK fusions, which are specific genetic changes found in some solid tumors and acute leukemia. Larotrectinib blocks the enzymes that cancer cells with these fusions need to grow, aiming to halt cancer growth. The trial is open to patients under 30 years old with untreated TRK fusion solid tumors or relapsed acute leukemia with TRK fusions. Participants should not have received any prior cancer treatment except surgery. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop all current medications, but certain medications are not allowed. You cannot take other anti-cancer agents, strong CYP3A4 inducers or inhibitors, or medications to prevent graft-versus-host disease. If you are on corticosteroids for leukemia, you can continue them until 24 hours before starting the trial treatment.

Is there any evidence suggesting that larotrectinib is likely to be safe for humans?

Research has shown that larotrectinib is safe for patients with TRK fusion cancers. Studies have found that both adults and children generally tolerate it well. Reports indicate that side effects are usually mild and manageable, meaning they are not severe for most people taking the medication. Larotrectinib has been used as the first treatment for this disease and has shown promising results in terms of safety and effectiveness. This suggests that, while all medications can have side effects, larotrectinib has a history of being safe for many patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Larotrectinib is unique because it specifically targets TRK fusion proteins, which are abnormal proteins driving cancer growth in certain tumors. Unlike traditional chemotherapy that broadly attacks rapidly dividing cells, larotrectinib zeroes in on these fusion proteins, potentially leading to fewer side effects and a more precise attack on cancer cells. Researchers are excited about larotrectinib because it represents a shift towards personalized medicine, offering hope for patients with TRK fusion cancers and acute leukemia who might not respond well to existing treatments.

What evidence suggests that larotrectinib might be an effective treatment for TRK fusion cancers and acute leukemia?

Research has shown that larotrectinib, the treatment under study in this trial, effectively treats TRK fusion-positive cancers. Studies have found that it significantly reduces tumors in patients of all ages and cancer types. It also extends patients' lives and generally causes mild side effects. Larotrectinib blocks TRK enzymes, which cancer cells need to grow. This treatment has shown promise in both adults and children with TRK fusion cancers. Overall, these findings support its potential effectiveness for the conditions studied in the trial. ^{2 4 6 7 8}

Who Is on the Research Team?

Theodore W Laetsch

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

This trial is for patients under 30 with untreated TRK fusion solid tumors or relapsed acute leukemia. They must have no prior cancer treatment except surgery, meet blood and organ function criteria, not be pregnant or breastfeeding, able to swallow capsules or have gastric access, and not on certain medications.

Inclusion Criteria

I am 30 years old or younger.

My seizures are well controlled and I've been on the same medication for at least 14 days.

My leukemia has come back or didn't respond to treatment, and tests show NTRK fusion.

Exclusion Criteria

You have had an organ transplant in the past.

I am taking medication to prevent rejection after a bone marrow transplant.

Patients currently receiving another investigational drug

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive larotrectinib orally or by nasogastric or gastric tube twice daily on days 1-28. Treatment repeats every 28 days for up to 26 cycles.

Up to 24 months

Monthly visits for each cycle

Surgical Resection

Patients whose tumors shrink sufficiently may undergo surgical resection of their tumor while on study.

Follow-up

Participants are monitored for safety and effectiveness after treatment completion at 3, 6, 12, 18, 24, 30, 36, and 48 months and annually thereafter for up to 5 years.

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Larotrectinib

Trial Overview The study tests Larotrectinib's effectiveness in blocking TRK enzymes to stop cancer cell growth in those with specific genetic markers (NTRK1, NTRK2, NTRK3 fusions). It includes young patients who haven't tried other treatments and whose disease has measurable indicators of progress.

How Is the Trial Designed?

Group I: Treatment (larotrectinib) Experimental Treatment 1 Intervention

Patients receive larotrectinib PO or by NG or G-tube BID on days 1-28. Treatment repeats every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity, or complete surgical resection of tumor.

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

Approved in United States as Vitrakvi for:

• Solid tumors with NTRK gene fusions

Approved in European Union as Vitrakvi for:

• Solid tumors with NTRK gene fusions

Who Is Running the Clinical Trial?

Children's Oncology Group

Lead Sponsor

Trials

467

Recruited

241,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Larotrectinib shows promising efficacy for treating solid tumors with NTRK gene fusions, with a 12-month progression-free survival (PFS) rate of 66.6% consistent between 2018 predictions and 2020 observed data from 102 patients across 15 tumor types.

While long-term PFS predictions varied due to differences in tumor responses, the overall survival (OS) predictions were reliable, with a 48-month OS rate of 67.2% aligning closely with observed data, indicating larotrectinib's potential for sustained effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Estimating Long-Term Survival Outcomes for Tumor-Agnostic Therapies: Larotrectinib Case Study. Briggs, A., Paracha, N., Rosettie, K., et al.[2022]

Larotrectinib (VITRAKVI®) is a targeted therapy specifically designed to inhibit tropomyosin receptor kinases (TRK) in patients with cancers that have neurotrophic receptor tyrosine kinase (NTRK) gene fusions, making it a promising option for both adults and children.

Approved in November 2018 in the USA, larotrectinib is indicated for metastatic solid tumors with NTRK gene fusions when no other satisfactory treatments are available, highlighting its role as a critical option for patients with limited alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Larotrectinib: First Global Approval. Scott, LJ.[2020]

Larotrectinib and entrectinib, first-generation TRK inhibitors, are effective first-line treatments for advanced non-small cell lung cancer (NSCLC) with TRK gene fusions, showing rapid and long-lasting clinical benefits.

A safety analysis of 807 reports revealed that the most common adverse reactions were dizziness and pain, with no significant long-term safety concerns noted, indicating a favorable risk-benefit profile for these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Safety Profiles of Two First-Generation NTRK Inhibitors: Analysis of Individual Case Safety Reports from the FDA Adverse Event Reporting System (FAERS) Database. Liguori, V., Gaio, M., Zinzi, A., et al.[2023]

Larotrectinib (VITRAKVI) is a highly effective treatment for patients with Trk fusion-positive cancers, showing a remarkable response rate of 75% regardless of cancer type, age, or gender.

The study developed a new LC-MS/MS method for accurately measuring Larotrectinib levels and assessing its metabolic stability, revealing a moderate extraction ratio and a half-life of approximately 48.8 minutes in human liver microsomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic Stability Assessment of Larotrectinib Using Liquid Chromatography Tandem Mass Spectrometry. Attwa, MW., Kadi, AA., Darwish, HW.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5857389/

Efficacy of Larotrectinib in TRK Fusion–Positive Cancers in ... Larotrectinib had marked and durable antitumor activity in patients with TRK fusion–positive cancer, regardless of the age of the patient or of the tumor type.

2. sciencedirect.com sciencedirect.com/science/article/pii/S0959804925001194

Efficacy and safety of larotrectinib in patients with TRK ... Larotrectinib demonstrated long durability, extended survival and manageable safety in patients with TRK fusion GI cancer, including those with MSI-H CRC.

3. esmoopen.com esmoopen.com/article/S2059-7029(25)00979-2/fulltext

Efficacy and safety of larotrectinib as first-line treatment for ... We report the first analysis of the efficacy and safety of larotrectinib in adult and paediatric patients with TRK fusion cancer who have not ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12165012/

The potential long-term comparative effectiveness of ... The tyrosine receptor kinase (TRK) inhibitor larotrectinib demonstrated improvements in life expectancy and health utility in patients with TRK fusion–positive ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.6094

Efficacy and safety of larotrectinib in patients with TRK ... Laro demonstrates rapid and durable responses, extended survival, and a favorable safety profile in pts with TRK fusion DTC.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40408921/

Efficacy and safety of larotrectinib as first-line treatment for ... Larotrectinib achieved extremely durable responses, extended survival and had a favourable safety profile in treatment-naïve patients with TRK fusion cancers.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02576431

NCT02576431 | A Study to Test the Effect of the Drug ... This research study is done to test how well different types of cancer respond to the drug called larotrectinib. The cancer must have a change in a ...

8. targetedonc.com targetedonc.com/view/larotrectinib-shows-robust-efficacy-and-safety-in-trk-fusion-cancer

Larotrectinib Shows Robust Efficacy and Safety in TRK ... Larotrectinib shows promising efficacy and safety as a first-line treatment for TRK fusion cancer in both adults and children.