Clinical trial NCT02122913: A Study to Test the Safety of the Investigational Drug Larotrectinib in Adults That May Treat Cancer
Official title: A Phase 1 Study of the Oral TRK Inhibitor Larotrectinib in Adult Patients With Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumors Harboring NTRK Fusion
Keywords: Advanced solid tumors
Neurotrophic tyrosine receptor kinase (NTRK)
NTRK1
NTRK2
NTRK3
Fusion Positive
TRK fusion
TRKA
TRKB
TRKC
ETV6
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2014-04-25
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This research study is done to test the safety of the drug larotrectinib in adult cancer patients. The drug may be used to treat cancer with a change in a particular gene (NTRK1, NTRK2 or NTRK3), because it blocks the action of these genes in cancer cells. The study also investigates how the drug is absorbed and processed in the human body. This is the first study to test larotrectinib in humans with cancer, for whom no other effective therapy exists.

Detailed description: The trial will be conducted in 2 parts: an initial dose escalation phase of larotrectinib in subjects with advanced solid tumors will be followed by an expansion phase in subjects with solid tumors having a NTRK fusion.

The objectives of the study are to determine the safety, pharmacokinetic profile, recommended dose and efficacy of orally administered larotrectinib in patients with NTRK fusions.

Eligibility criteria: Inclusion Criteria:

* Adult patients with a locally advanced or metastatic solid tumor that has progressed or was nonresponsive to available therapies, are unfit for standard chemotherapy or for which no standard or available curative therapy exists
* Proof of a malignancy harboring a NTRK fusion
* Eastern Cooperative Oncology Group (ECOG) score of 0, 1 or 2 and a life expectancy of at least 3 months
* Adequate hematologic, hepatic, and renal function

Exclusion Criteria:

* Patients with unstable primary central-nervous-system tumors or metastasis, exceptions possible
* Clinically significant active cardiovascular disease or history of myocardial infarction
* Active uncontrolled systemic bacterial, viral, or fungal infection
* Current treatment with a strong CYP3A4 inhibitor or inducer
* Pregnancy or lactation

Primary outcomes:
measure: Number of participants with adverse events
timeFrame: 25 months
measure: Severity of adverse events
timeFrame: 25 months
measure: Maximum tolerated dose (MTD)
timeFrame: 25 months
measure: Recommended dose for dose expansion
timeFrame: 25 months
Secondary outcomes:
measure: Maximum concentration of larotrectinib in plasma (Cmax)
timeFrame: Predose and 0.25, 0.5, 1, 2, 4, 6 and 8 hours after drug administration on Days 1 and 8 of Cycle 1
measure: Time to maximum concentration of larotrectinib in plasma (Tmax)
timeFrame: Predose and 0.25, 0.5, 1, 2, 4, 6 and 8 hours after drug administration on Days 1 and 8 of Cycle 1
measure: Half-life of larotrectinib in plasma (t1/2)
timeFrame: Predose and 0.25, 0.5, 1, 2, 4, 6 and 8 hours after drug administration on Days 1 and 8 of Cycle 1
measure: Area under the concentration versus time curve of larotrectinib in plasma (AUC)
timeFrame: Predose and 0.25, 0.5, 1, 2, 4, 6 and 8 hours after drug administration on Days 1 and 8 of Cycle 1
measure: Overall Response Rate (ORR)
timeFrame: Up to 60 months
measure: Duration of Response (DOR)
timeFrame: Up to 60 months
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
Study officials:
References:
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citation: Le X, Baik C, Bauman J, Gilbert J, Brose MS, Grilley-Olson JE, Patil T, McDermott R, Raez LE, Johnson JM, Shen L, Tahara M, Ho AL, Norenberg R, Dima L, Brega N, Drilon A, Hong DS. Larotrectinib Treatment for Patients With TRK Fusion-Positive Salivary Gland Cancers. Oncologist. 2022 May 10;29(6):e779-88. doi: 10.1093/oncolo/oyac080. Online ahead of print.
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citation: Bebb DG, Banerji S, Blais N, Desmeules P, Gill S, Grin A, Feilotter H, Hansen AR, Hyrcza M, Krzyzanowska M, Melosky B, Noujaim J, Purgina B, Ruether D, Simmons CE, Soulieres D, Torlakovic EE, Tsao MS. Canadian Consensus for Biomarker Testing and Treatment of TRK Fusion Cancer in Adults. Curr Oncol. 2021 Jan 15;28(1):523-548. doi: 10.3390/curroncol28010053.
citation: Perreault S, Chami R, Deyell RJ, El Demellawy D, Ellezam B, Jabado N, Morgenstern DA, Narendran A, Sorensen PHB, Wasserman JD, Yip S. Canadian Consensus for Biomarker Testing and Treatment of TRK Fusion Cancer in Pediatric Patients. Curr Oncol. 2021 Jan 9;28(1):346-366. doi: 10.3390/curroncol28010038.
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citation: Drilon A, Laetsch TW, Kummar S, DuBois SG, Lassen UN, Demetri GD, Nathenson M, Doebele RC, Farago AF, Pappo AS, Turpin B, Dowlati A, Brose MS, Mascarenhas L, Federman N, Berlin J, El-Deiry WS, Baik C, Deeken J, Boni V, Nagasubramanian R, Taylor M, Rudzinski ER, Meric-Bernstam F, Sohal DPS, Ma PC, Raez LE, Hechtman JF, Benayed R, Ladanyi M, Tuch BB, Ebata K, Cruickshank S, Ku NC, Cox MC, Hawkins DS, Hong DS, Hyman DM. Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children. N Engl J Med. 2018 Feb 22;378(8):731-739. doi: 10.1056/NEJMoa1714448.
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