What side effects are associated with this type of intervention?

Common treatments for solid tumors, particularly those involving gene inhibition like Larotrectinib, often include targeted therapies and immunotherapies. Known side effects of these treatments can include partial alopecia, hair curling, and dyspigmentation. Additionally, patients may experience fatigue, nausea, and anemia. Immunotherapies may also cause patchy hypopigmentation of the skin and hair, as well as alopecia. These side effects are generally manageable and vary in severity.

What prior FDA approvals exist?

Larotrectinib is an FDA-approved drug specifically targeting NTRK gene fusions in solid tumors. Similar treatments include entrectinib, another TRK inhibitor approved for NTRK fusion-positive solid tumors. These drugs are part of a broader category of targeted therapies that act on specific genetic alterations within tumors, offering a more personalized approach to cancer treatment. Other examples of targeted therapies include pembrolizumab for tumors with high tumor mutational burden (TMB) or DNA mismatch repair deficiency, and various PARP inhibitors like rucaparib and niraparib for cancers with BRCA mutations.

What other types of research exist?

Promising alternatives to Larotrectinib for solid tumors with NTRK gene fusions include: 1) Afatinib, which has shown partial responses in NRG1-positive lung cancer, and 2) Seribantumab, currently in clinical trial development for NRG1 fusions. Additionally, immune checkpoint inhibitors like anti-PD-1 or anti-PD-L1 therapies may be considered, especially in combination with other treatments.

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Kinase Inhibitor

Larotrectinib for Solid Cancers (NAVIGATE Trial)

Phase 2

Waitlist Available

Research Sponsored by Bayer

Eligibility Criteria Checklist

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

Must have

Performance Status: ECOG score ≤ 3, KPS ≥ 50% if enrolled with primary CNS tumor

Willingness to use double effective birth control methods

Must not have

Investigational agent or anticancer therapy within 2 weeks prior to larotrectinib

Prior progression on TRK inhibitors

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 120 months

Awards & highlights

No Placebo-Only Group

Summary

This trial tests how well larotrectinib works for children and adults with advanced solid tumors that have specific gene changes. The drug blocks the actions of these genes to stop cancer growth.

Who is the study for?

This trial is for adults and children with solid tumors that have a specific gene change (NTRK1, NTRK2 or NTRK3). Participants must have tried standard treatments without success or be unlikely to benefit from them. They need at least one measurable tumor lesion, stable organ function, and no uncontrolled illnesses. People with certain infections or recent heart issues can't join.

What is being tested?

The study tests larotrectinib's effectiveness on cancers with an NTRK gene fusion. Larotrectinib aims to block these genes in cancer cells to treat the disease. The trial includes patients who've had prior treatments like chemotherapy or radiation.

What are the potential side effects?

While not explicitly listed here, side effects of larotrectinib may include fatigue, dizziness, nausea, liver enzyme elevation, constipation, anemia among others based on its action as a tyrosine kinase inhibitor which can affect various body systems.

Eligibility Criteria

Inclusion Criteria

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

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I can take care of myself but can't do any physical work or I have a brain tumor and can still do some daily activities.

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I am willing to use two effective methods of birth control.

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I am 18 years old or older.

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My cancer has a specific gene change known as NTRK fusion.

Exclusion Criteria

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

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I haven't taken any cancer drugs or been in a trial for 2 weeks.

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My cancer progressed despite TRK inhibitor treatment.

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I do not have any uncontrolled infections or unstable heart conditions.

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I do not have another cancer that could interfere with the treatment's effectiveness.

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I have a history of HIV, HBV, or HCV infection.

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I have brain metastases that are causing symptoms or are unstable.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 120 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 120 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 120 months for reporting.

Treatment Details

Study Objectives

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

Secondary study objectives

Concordance coefficient

Duration of response (DOR): determined for subjects with best overall response of confirmed CR or PR by 1) an independent radiology review committee and 2) the treating Investigator

Awards & Highlights

No Placebo-Only Group

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

Trial Design

11Treatment groups

Experimental Treatment

Group I: Arm 9_Solid tumors without confirmed NTRK fusionExperimental Treatment1 Intervention

Patients eligible for arms 1 to 8, but with documented NTRK fusion from a laboratory where CLIA or equivalent certification cannot be confirmed by the sponsor at the time of consent (arm closed)

Group II: Arm 8_Other tumorsExperimental Treatment1 Intervention

Patients with e.g. kidney cancer, squamous cell cancer of head or neck or ovarian solid tumors harboring NTRK fusions (arm closed)

Group III: Arm 7_Primary CNSExperimental Treatment1 Intervention

Patients with solid tumors in the primary central nervous system (CNS) harboring NTRK fusions (arm closed)

Group IV: Arm 6_BiliaryExperimental Treatment1 Intervention

Patients with solid biliary tumors harboring NTRK fusions (arm closed)

Group V: Arm 5_SalivaryExperimental Treatment1 Intervention

Patients with solid salivary tumors harboring NTRK fusions (arm closed)

Group VI: Arm 4_ColorectalExperimental Treatment1 Intervention

Patients with solid colorectal tumors harboring NTRK fusions (arm closed)

Group VII: Arm 3_SarcomaExperimental Treatment1 Intervention

Patients with soft-tissue sarcoma harboring NTRK fusions (arm closed)

Group VIII: Arm 2_ThyroidExperimental Treatment1 Intervention

Patients with solid thyroid tumors harboring NTRK fusions (arm closed)

Group IX: Arm 1_NSCLCExperimental Treatment1 Intervention

Patients with solid non-small cell lung cancer (NSCLC) harboring NTRK fusions (arm closed)

Group X: Arm 11_Bone health cohortExperimental Treatment1 Intervention

Patients with all tumor types harboring NTRK fusions, not eligible for the main prospective cohort, including patients with non-measurable disease

Group XI: Arm 10_Prospective cohortExperimental Treatment1 Intervention

Patients with melanoma, non secretory breast and colorectal cancer or other tumor types harboring NTRK fusions, except soft tissue sarcoma, salivary gland and thyroid cancer (arm closed)

0 / 10Eligibility 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

The most common treatments for solid tumors often involve targeted therapies that inhibit specific genetic mutations driving cancer growth. Larotrectinib, for example, targets NTRK gene fusions, blocking the action of these genes in cancer cells and thereby inhibiting tumor growth. This approach is crucial for solid tumor patients as it allows for more personalized and effective treatment options, potentially leading to better outcomes and fewer side effects compared to traditional chemotherapy. Other targeted therapies may focus on mutations in genes like EGFR, ALK, and ROS1, each designed to disrupt specific pathways critical for tumor survival and proliferation.

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