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

NCT02097810 | Completed Phase 1

• 2 other identifiers: RXDX-101-01GO40784
• Study Type: interventional
• Target: 84
• Locations: 2 countries
• Sites: 10

Brief 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.

Conditions

Locally Advanced Solid Tumors; Metastatic Solid Tumors

Outcome Measures

Primary Outcomes (4)

• Dose-Limiting Toxicity (DLT)

  Determine dose-limiting toxicities of entrectinib.

  28 days following first dose of entrectinib

• Maximum Tolerated Dose (MTD)

  Determine MTD of entrectinib

  28 days following first dose of entrectinib

• Recommended Phase 2 Dose (RP2D)

  Determine RP2D of entrectinib.

  Approx. 6 months

• Overall Response Rate (ORR) in Dose Expansion

  Per RECIST v1.1 as assessed by Investigator.

  Approx. 2 months

Secondary Outcomes (5)

• Plasma Concentrations of Entrectinib

  Cycle 1 Days 1, 7, 14, 28

• Disease Control

  Approx. 2 years

• Duration of Response

  Approx. 2 years

• Overall Survival (OS)

  Approx. 2 years

• Progression-Free Survival (PFS)

  Approx. 2 years

Study Arms (1)

Entrectinib (RXDX-101)

EXPERIMENTAL

Oral entrectinib (RXDX-101)

Drug: Entrectinib

Interventions

Entrectinib DRUG

Also known as: TrkA/TrkB/TrkC/ROS1/ALK inhibitor

Entrectinib (RXDX-101)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (10)

UC Irvine Medical Center

Orange, California, 92868, United States

Location

University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94158, United States

Location

University Of Colorado

Aurora, Colorado, 80045, United States

Location

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

Florida Cancer Specialists - Sarasota

Sarasota, Florida, 34232, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

University of Texas M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Samsung Medical Center

Seoul, 06531, South Korea

Location

Related Publications (6)

• Doebele RC, Perez L, Trinh H, Martinec M, Martina R, Riehl T, Krebs MG, Meropol NJ, Wong WB, Crane G. Comparative effectiveness analysis between entrectinib clinical trial and crizotinib real-world data in ROS1+ NSCLC. J Comp Eff Res. 2021 Dec;10(17):1271-1282. doi: 10.2217/cer-2021-0131. Epub 2021 Aug 24.

  PMID: 34427452 DERIVED

• Dziadziuszko R, Krebs MG, De Braud F, Siena S, Drilon A, Doebele RC, Patel MR, Cho BC, Liu SV, Ahn MJ, Chiu CH, Farago AF, Lin CC, Karapetis CS, Li YC, Day BM, Chen D, Wilson TR, Barlesi F. Updated Integrated Analysis of the Efficacy and Safety of Entrectinib in Locally Advanced or Metastatic ROS1 Fusion-Positive Non-Small-Cell Lung Cancer. J Clin Oncol. 2021 Apr 10;39(11):1253-1263. doi: 10.1200/JCO.20.03025. Epub 2021 Mar 1.

  PMID: 33646820 DERIVED

• Drilon A, Siena S, Dziadziuszko R, Barlesi F, Krebs MG, Shaw AT, de Braud F, Rolfo C, Ahn MJ, Wolf J, Seto T, Cho BC, Patel MR, Chiu CH, John T, Goto K, Karapetis CS, Arkenau HT, Kim SW, Ohe Y, Li YC, Chae YK, Chung CH, Otterson GA, Murakami H, Lin CC, Tan DSW, Prenen H, Riehl T, Chow-Maneval E, Simmons B, Cui N, Johnson A, Eng S, Wilson TR, Doebele RC; trial investigators. Entrectinib in ROS1 fusion-positive non-small-cell lung cancer: integrated analysis of three phase 1-2 trials. Lancet Oncol. 2020 Feb;21(2):261-270. doi: 10.1016/S1470-2045(19)30690-4. Epub 2019 Dec 11.

  PMID: 31838015 DERIVED

• Doebele RC, Drilon A, Paz-Ares L, Siena S, Shaw AT, Farago AF, Blakely CM, Seto T, Cho BC, Tosi D, Besse B, Chawla SP, Bazhenova L, Krauss JC, Chae YK, Barve M, Garrido-Laguna I, Liu SV, Conkling P, John T, Fakih M, Sigal D, Loong HH, Buchschacher GL Jr, Garrido P, Nieva J, Steuer C, Overbeck TR, Bowles DW, Fox E, Riehl T, Chow-Maneval E, Simmons B, Cui N, Johnson A, Eng S, Wilson TR, Demetri GD; trial investigators. Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1-2 trials. Lancet Oncol. 2020 Feb;21(2):271-282. doi: 10.1016/S1470-2045(19)30691-6. Epub 2019 Dec 11.

  PMID: 31838007 DERIVED

• Drilon A, Li G, Dogan S, Gounder M, Shen R, Arcila M, Wang L, Hyman DM, Hechtman J, Wei G, Cam NR, Christiansen J, Luo D, Maneval EC, Bauer T, Patel M, Liu SV, Ou SH, Farago A, Shaw A, Shoemaker RF, Lim J, Hornby Z, Multani P, Ladanyi M, Berger M, Katabi N, Ghossein R, Ho AL. What hides behind the MASC: clinical response and acquired resistance to entrectinib after ETV6-NTRK3 identification in a mammary analogue secretory carcinoma (MASC). Ann Oncol. 2016 May;27(5):920-6. doi: 10.1093/annonc/mdw042. Epub 2016 Feb 15.

  PMID: 26884591 DERIVED

• Farago AF, Le LP, Zheng Z, Muzikansky A, Drilon A, Patel M, Bauer TM, Liu SV, Ou SH, Jackman D, Costa DB, Multani PS, Li GG, Hornby Z, Chow-Maneval E, Luo D, Lim JE, Iafrate AJ, Shaw AT. Durable Clinical Response to Entrectinib in NTRK1-Rearranged Non-Small Cell Lung Cancer. J Thorac Oncol. 2015 Dec;10(12):1670-4. doi: 10.1097/01.JTO.0000473485.38553.f0.

  PMID: 26565381 DERIVED

MeSH Terms

Interventions

entrectinib

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2014
• First Posted: March 27, 2014
• Study Start: July 28, 2014
• Primary Completion: June 2, 2020
• Study Completion: June 2, 2020
• Last Updated: June 9, 2021

Record last verified: 2021-06

Locations

US (9); KR (1)