Treatment of advanced solid tumors with larotrectinib for NTRK gene amplification
A Phase II Basket Study of the Oral TRK Inhibitor Larotrectinib (BAY2757556) in Subjects With NTRK Amplification Positive and Pan-TRK Positive Tumors
This study is testing if a new drug called larotrectinib can help people with advanced solid tumors that have a specific gene change called NTRK amplification.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 13 (estimated) |
| Ages | 16 Years and up |
| Sex | All |
| Sponsor | M.D. Anderson Cancer Center Academic / other |
| Drugs / interventions | larotrectinib, chemotherapy, radiation |
| Locations | 1 site (Houston, Texas) |
| Trial ID | NCT04879121 on ClinicalTrials.gov |
What this trial studies
This phase II trial evaluates the effectiveness of larotrectinib in patients with locally advanced or metastatic solid tumors that have NTRK gene amplification. The study aims to determine the overall response rate, duration of response, and safety profile of larotrectinib. Patients will be assessed for tumor response using established criteria, and exploratory objectives include characterizing NTRK amplification and TRK signaling in tumor biopsies. The trial is designed to provide insights into the potential benefits of larotrectinib for this specific patient population.
Who should consider this trial
Good fit: Ideal candidates include individuals aged 16 and older with locally advanced or metastatic solid tumors that have confirmed NTRK gene amplification.
Not a fit: Patients without NTRK gene amplification or those who have not received prior standard therapy may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could provide a targeted therapy option for patients with NTRK amplification positive tumors, potentially improving their outcomes.
How similar studies have performed: Other studies have shown promising results with larotrectinib in similar patient populations, indicating a potential for success.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * At least 16 years of age * Locally-advanced or metastatic malignancy with an NTRK1, NTRK2, or NTRK3 gene amplification identified through molecular assays (such as IHC and any next-generation sequencing \[NGS\] platform, reference lab NGS, or in house NGS platform) as routinely performed at The University of Texas MD Anderson Cancer Center or other similarly-certified laboratories. The minimum level of amplification is 7 copies. This rationale of amplification level is based on data from MOCLIA at The University of Texas MD Anderson Cancer Center * Must have received prior standard therapy appropriate for tumor type and stage of disease, or, in the opinion of the investigator, is unlikely to tolerate or derive clinically meaningful benefit from appropriate standard of care therapy * Must have at least one measurable lesion as defined by RECIST v1.1. Subjects with primary CNS tumors should meet the following criteria: * Must have received prior treatment including radiation and/or chemotherapy, with radiation completed \> 12 weeks prior to cycle 1 day 1 (C1D1) of therapy, as recommended or appropriate for the tumor type * Must have \>= 1 site of bi-dimensionally measurable disease (confirmed by magnetic resonance imaging \[MRI\] and evaluable by RANO), with the size of at least one of the measurable lesions \>= 1 cm in each dimension * Must have imaging study within 28 days before enrollment. If on steroid therapy, the dose must be stable for at least five days immediately before and during the imaging study * Eastern Cooperative Oncology Group (ECOG) score =\< 3. If enrolled with primary CNS tumor to be assessed by RANO, Karnofsky performance score (KPS) \>= 70 % * Archived tumor tissue. If archival tissue is unavailable, an on-study tumor biopsy should be attempted if it can be safely performed * Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) \< 2.5 x upper limit of normal (ULN) or \< 5 x ULN if liver function abnormalities are due to underlying malignancy * Total bilirubin \< 2.5 x ULN, except in cases of biliary obstruction. Subjects with a known history of Gilberts disease and an isolated elevation of indirect bilirubin are eligible * Serum creatinine \< 2.0 x ULN or estimated glomerular filtration rate \>= 30 mL/minute using the Cockcroft-Gault formula * Ability to comply with outpatient treatment, laboratory monitoring, and required clinic visits for the duration of study participation * Willingness of men and women of reproductive potential to use two effective birth control methods, one used by the subject and another by his/her partner, for the duration of treatment and for 3 months following study completion Exclusion Criteria: * Investigational agent or anticancer therapy within 2 weeks prior to the planned start of larotrectinib or five half-lives, whichever is shorter, and without clinically significant toxicities from that therapy * Prior progression while receiving approved or investigational tyrosine kinase inhibitors targeting TRK. However, subjects who received less than 28 days of such treatment and discontinued because of intolerance or toxicity are eligible * Symptomatic or unstable brain metastases that needs corticosteroid usage. Subjects with asymptomatic brain metastases or primary CNS tumors are eligible * Uncontrolled concurrent malignancy that would limit assessment of efficacy. Allowed diseases may include, but are not limited to in situ cancers of cervix, breast, or skin, superficial bladder cancer, limited-stage prostate cancer, and basal or squamous cancers of the skin * Active uncontrolled systemic bacterial, viral, or fungal infection, unstable cardiovascular disease or other systemic disease that would limit compliance with study procedures. Unstable cardiovascular disease is defined as: * Persistently uncontrolled hypertension defined as systolic blood pressure (BP) \> 150 mmHg and/or diastolic BP \> 100 mmHg despite antihypertensive therapy * Myocardial infarction within 3 months of screening * Stroke within 3 months of screening * Inability to discontinue treatment with a strong cytochrome P450 (CYP450), 3A4 (CYP3A4) inhibitor or inducer prior to start of treatment * Pregnancy or lactation
Where this trial is running
Houston, Texas
- M D Anderson Cancer Center — Houston, Texas, United States (Recruiting)
Study contacts
- Principal investigator: David S Hong — M.D. Anderson Cancer Center
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.