Larotrectinib for the Treatment of NTRK Amplification Positive, Locally Advanced or Metastatic Solid Tumors
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age16+
SponsorM.D. Anderson Cancer Center
About this trial
This phase II trial studies the effect of larotrectinib in treating patients with NTRK gene amplification positive solid tumors that have spread to nearby tissues or lymph nodes (locally advanced) or other places in the body (metastatic). Larotrectinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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 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
Disqualifiers
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
Trial design
Design model
Single group
Treatments tested in this trial
Larotrectinib Sulfate
DrugGiven PO
Treatment groups
13 Participants
are divided into 1 treatment groupGroup A: Treatment (larotrectinib sulfate)Experimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Overall response
Will be scored by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Time frame
Up to 2 years post-treatmentSecondary outcomes
1
Best overall response of confirmed complete response or partial response
Will be determined using RECIST version 1.1 or Response Assessment in Neuro-Oncology criteria, as appropriate to tumor type. A bias-correcting estimate of the best overall response rate and its one-sided 90% confidence interval will be calculated using an exact inference method that appropriately accounts for Bayesian optimal phase II design.
Time frame
Up to 2 years post-treatment2
Duration of response
Will be calculated for subjects who achieve confirmed complete response or partial response, and Kaplan-Meier estimates, mean and median duration, and two-sided 95% confidence intervals will be generated.
Time frame
From the date complete response or partial response is first noted (whichever response is recorded first), to the date that recurrence or progressive disease is first documented or to date of death, assessed up to 2 years3
Growth modulation index
Will be defined as the ratio of time to progression (TTP) with nth line of therapy (TTPn) to the most recent prior line of therapy and summarized with mean, median, standard error, and two-sided 95% confidence interval.
Time frame
Up to 2 years post-treatment4
Progression-free survival
Kaplan-Meier estimates, mean and median duration, and two-sided 95% confidence intervals will be generated. In patients who have received prior therapy, corresponding Kaplan-Meier plots, mean and median duration with 95% confidence intervals will be used to compare the duration of progression-free survival following initiation of larotrectinib to that following the line of therapy immediately preceding larotrectinib.
Time frame
From initiation of larotrectinib to disease progression or death due to any cause, whichever occurs first, assessed up to 2 yearsSponsors and contacts
Click on the lead sponsor to view all of their trials.
M.D. Anderson Cancer Center
Lead sponsor
National Cancer Institute (NCI)
Collaborator
Source ClinicalTrials.gov