Study of Oral RXDX-101 in Adult Patients With Locally Advanced or Metastatic Cancer Targeting NTRK1, NTRK2, NTRK3, ROS1, or ALK Molecular Alterations. (STARTRK-1)

• ClinicalTrials.gov Identifier: NCT02097810
• Recruitment Status: Completed
• First Posted: March 27, 2014
• Last Update Posted: June 9, 2021
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: March 21, 2014
• First Posted Date: March 27, 2014
• Last Update Posted Date: June 9, 2021
• Actual Study Start Date: July 28, 2014
• Actual Primary Completion Date: June 2, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 28, 2016)

• Dose-Limiting Toxicity (DLT) [ Time Frame: 28 days following first dose of entrectinib ]
  Determine dose-limiting toxicities of entrectinib.
• Maximum Tolerated Dose (MTD) [ Time Frame: 28 days following first dose of entrectinib ]
  Determine MTD of entrectinib
• Recommended Phase 2 Dose (RP2D) [ Time Frame: Approx. 6 months ]
  Determine RP2D of entrectinib.
• Overall Response Rate (ORR) in Dose Expansion [ Time Frame: Approx. 2 months ]
  Per RECIST v1.1 as assessed by Investigator.

Original Primary Outcome Measures (submitted: March 24, 2014)

• Phase 1: Dose-Limiting Toxicity (DLT) [ Time Frame: 28 days following first dose of RXDX-101 ]
  Determine dose-limiting toxicities of RXDX-101.
• Phase 1: Maximum Tolerated Dose (MTD) [ Time Frame: 28 days following first dose of RXDX-101 ]
  Determine MTD of RXDX-101
• Phase 1: Recommended Phase 2 Dose (RP2D) [ Time Frame: Appox. 6 months ]
  Determine RP2D of RXDX-101.
• Phase 2a: Objective response [ Time Frame: Approx. 2 years ]
  Proportion of patients with a confirmed Complete Response (CR) or Partial Response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as assessed by the Investigator.

Current Secondary Outcome Measures (submitted: October 28, 2016)

• Plasma Concentrations of Entrectinib [ Time Frame: Cycle 1 Days 1, 7, 14, 28 ]
• Disease Control [ Time Frame: Approx. 2 years ]
  Per RECIST v1.1 as assessed by Investigator.
• Duration of Response [ Time Frame: Approx. 2 years ]
  Per RECIST v1.1 as assessed by Investigator.
• Overall Survival (OS) [ Time Frame: Approx. 2 years ]
• Progression-Free Survival (PFS) [ Time Frame: Approx. 2 years ]

Original Secondary Outcome Measures (submitted: March 24, 2014)

• Plasma concentrations of RXDX-101 [ Time Frame: Cycle 1 Days 1, 7, 14, 28 ]
• Progression-Free Survival (PFS) [ Time Frame: Approx. 2 years ]
  Per RECIST v1.1 as assessed by Investigator.
• Overall Survival (OS) [ Time Frame: Approx. 2 years ]
  Per RECIST v1.1 as assessed by Investigator.
• Disease Control [ Time Frame: Approx. 2 years ]
  Per RECIST v1.1 as assessed by Investigator.
• Duration of Response [ Time Frame: Approx. 2 years ]
  Per RECIST v1.1 as assessed by Investigator.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Locally Advanced Solid Tumors
• Metastatic Solid Tumors

Intervention

Drug: Entrectinib

Other Name: TrkA/TrkB/TrkC/ROS1/ALK inhibitor

Study Arms

Experimental: Entrectinib (RXDX-101)

Oral entrectinib (RXDX-101)

Intervention: Drug: Entrectinib

Publications *

• 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. Erratum In: J Comp Eff Res. 2022 May;11(7):545-548.
• 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.
• 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. Erratum In: Lancet Oncol. 2020 Feb;21(2):e70. Lancet Oncol. 2020 Jul;21(7):e341.
• 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. Erratum In: Lancet Oncol. 2020 Feb;21(2):e70. Lancet Oncol. 2020 Jul;21(7):e341. Lancet Oncol. 2020 Aug;21(8):e372. Lancet Oncol. 2021 Oct;22(10):e428.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 7, 2019): 84
• Original Estimated Enrollment (submitted: March 24, 2014): 125
• Actual Study Completion Date: June 2, 2020
• Actual Primary Completion Date: June 2, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Korea, Republic of, United States
• Removed Location Countries: Spain

Administrative Information

• NCT Number: NCT02097810
• Other Study ID Numbers: RXDX-101-01; GO40784 ( Other Grant/Funding Number: Hoffmann-La Roche )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Hoffmann-La Roche
• Original Responsible Party: Same as current
• Current Study Sponsor: Hoffmann-La Roche
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: June 2021