Study of Oral RXDX-101 in Adult Patients With Locally Advanced or Metastatic Cancer Targeting NTRK1, NTRK2, NTRK3, ROS1, or ALK Molecular Alterations.

Metastatic Solid Tumors Clinical Trial

— STARTRK-1  

Official title:

A Phase 1, Multicenter, Open-Label Study of Oral Entrectinib (RXDX-101) in Adult Patients With Locally Advanced or Metastatic Cancer Confirmed to be Positive for NTRK1, NTRK2, NTRK3, ROS1, or ALK Molecular Alterations

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02097810
• Other study ID #: RXDX-101-01
• Secondary ID: GO40784
• Status: Completed
• Phase: Phase 1
• Start date: July 28, 2014
• Est. completion date: June 2, 2020

Study information

• Verified date: June 2021
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Entrectinib (RXDX-101) is an orally available inhibitor of the tyrosine kinases TrkA (coded by the gene NTRK1), TrkB (coded by the gene NTRK2), TrkC (coded by the gene NTRK3), ROS1 (coded by the gene ROS1), and ALK (coded by the gene ALK). Molecular alterations to one or more of these targets are present in several different tumor types, including non-small cell lung cancer (NSCLC), colorectal cancer (CRC), prostate cancer, papillary thyroid cancer, pancreatic cancer, and neuroblastoma. Patients with locally advanced or metastatic cancer with a detectable molecular alteration in targets of interest may be eligible for enrollment. Phase 1 will assess safety and tolerability of entrectinib via standard dose escalation scheme and determine the recommended Phase 2 dose. Safety and efficacy will be assessed in the dose expansion portion of the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 84
• Est. completion date: June 2, 2020
• Est. primary completion date: June 2, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of locally advanced or metastatic solid tumors that have a NTRK1, NTRK2, NTRK3, ROS1, or ALK molecular alteration.
• Measurable disease according to RECIST version 1.1.
• Prior cancer therapy is allowed, including crizotinib, ceritinib, and investigational drugs.
• Prior radiotherapy is allowed
• Patients with controlled asymptomatic central nervous system involvement are allowed.
• Resolution of all acute toxic effects (excluding alopecia) of any prior anti-cancer therapy to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Grade less than or equal to 1.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) = 2.
• Adult patients age 18 years or older.
• Life expectancy of at least 3 months.

Key Exclusion Criteria:

• Current participation in another therapeutic clinical trial.
• Prior treatment with entrectinib.
• History of prolonged QTc interval (e.g., repeated demonstration of a QTc interval > 450 milliseconds).
• History of additional risk factors for torsade de pointes (e.g., family history of long QT syndrome).
• Known active infections (bacterial, fungal, viral including HIV positivity).
• Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would impact on drug absorption.
• Known interstitial lung disease, interstitial fibrosis, or history of tyrosine kinase inhibitor-induced pneumonitis.
• Peripheral neuropathy = Grade 2.

Related Conditions & MeSH terms

• Locally Advanced Solid Tumors
• Metastatic Solid Tumors
• Neoplasm Metastasis

Intervention

Drug:
• Entrectinib

Locations

Country	Name	City	State
Korea, Republic of	Samsung Medical Center	Seoul
United States	University Of Colorado	Aurora	Colorado
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of Texas M.D. Anderson Cancer Center	Houston	Texas
United States	Tennessee Oncology	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	UC Irvine Medical Center	Orange	California
United States	University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center	San Francisco	California
United States	Florida Cancer Specialists - Sarasota	Sarasota	Florida
United States	Georgetown University Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-Limiting Toxicity (DLT)	Determine dose-limiting toxicities of entrectinib.	28 days following first dose of entrectinib
Primary	Maximum Tolerated Dose (MTD)	Determine MTD of entrectinib	28 days following first dose of entrectinib
Primary	Recommended Phase 2 Dose (RP2D)	Determine RP2D of entrectinib.	Approx. 6 months
Primary	Overall Response Rate (ORR) in Dose Expansion	Per RECIST v1.1 as assessed by Investigator.	Approx. 2 months
Secondary	Plasma Concentrations of Entrectinib		Cycle 1 Days 1, 7, 14, 28
Secondary	Disease Control	Per RECIST v1.1 as assessed by Investigator.	Approx. 2 years
Secondary	Duration of Response	Per RECIST v1.1 as assessed by Investigator.	Approx. 2 years
Secondary	Overall Survival (OS)		Approx. 2 years
Secondary	Progression-Free Survival (PFS)		Approx. 2 years