Basket Study of Entrectinib (RXDX-101) for the Treatment of Patients With Solid Tumors Harboring NTRK 1/2/3 (Trk A/B/C), ROS1, or ALK Gene Rearrangements (Fusions) (STARTRK-2)

March 27, 2024 updated by: Hoffmann-La Roche

An Open-Label, Multicenter, Global Phase 2 Basket Study of Entrectinib for the Treatment of Patients With Locally Advanced or Metastatic Solid Tumors That Harbor NTRK1/2/3, ROS1, or ALK Gene Rearrangements

This is an open-label, multicenter, global Phase 2 basket study of entrectinib (RXDX-101) for the treatment of patients with solid tumors that harbor an NTRK1/2/3, ROS1, or ALK gene fusion. Patients will be assigned to different baskets according to tumor type and gene fusion.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

534

Phase

  • Phase 2

Expanded Access

No longer available outside the clinical trial. See expanded access record.

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Liverpool, New South Wales, Australia, 2170
        • Liverpool Hospital
      • New Lambton Heights, New South Wales, Australia, 2305
        • Newcastle Private Hospital
    • South Australia
      • Bedford Park, South Australia, Australia, 5042
        • Flinders Medical Centre
    • Victoria
      • Heidelberg, Victoria, Australia, 3084
        • Austin Health
  • Belgium
      • Edegem, Belgium, 2650
        • Antwerp University Hospital
  • China
      • Beijing, China, 100142
        • Beijing Cancer Hospital
      • Chengdu, China, 610041
        • Sichuan Provincial Cancer Hospital
      • Guangzhou, China, 510000
        • Cancer Center of Guangzhou Medical University
      • Harbin, China, 150081
        • Harbin Medical University Cancer Hospital
      • Shanghai, China, 200030
        • Shanghai Chest Hospital
      • Shanghai City, China, 200120
        • Fudan University Shanghai Cancer Center
      • Shenzhen, China, 510852
        • Shenzhen people's hospital
      • Tianjin, China, 300060
        • Tianjin Cancer Hospital
      • Wuhan City, China, 430023
        • Union Hospital Tongji Medical College Huazhong University of Science and Technology
      • Zhejiang, China, 310022
        • Zhejiang Cancer Hospital
  • France
      • Angers, France, 49055
        • Institut de Cancerologie de l Ouest
      • Bordeaux, France, 33076
        • Institut Bergonie; Oncologie
      • Lyon, France, 69373
        • Centre Leon Berard; Departement Oncologie Medicale
      • Marseille, France, 13015
        • Hôpital Nord - AP-HM Marseille#; Service d'Oncologie Multidisciplinaire
      • Marseille cedex 5, France, 13385
        • Hôpital de la Timone; Oncologie Médicale Hématologie & Soins Palliatifs
      • Montpellier cedex 5, France, 34298
        • Institut de Recherche en Cancerologie de Montpellier
      • Paris, France, 75231
        • Institut Curie; Oncologie Medicale
      • Saint Herblain, France, 44805
        • Institut De Cancerologie De L'ouest - Rene Gauducheau - Biology
      • Toulouse, France, 31059
        • Institut Claudius Regaud; Departement Oncologie Medicale
      • Villejuif cedex, France, 94805
        • Institut Gustave Roussy; Pathologie Thoracique
  • Germany
      • Berlin, Germany, 13125
        • Evang. Lungenklinik Berlin Klinik für Pneumologie
      • Dresden, Germany, 01307
        • Universitaetsklinikum Carl Gustav Carus TU Dresden
      • Göttingen, Germany, 37075
        • Universitaetsmedizin Goettingen; Abteilung Haematologie und Onkologie
      • Heidelberg, Germany, 69120
        • NCT Uniklinikum Heidelberg; Medizinische Onkologie
      • Köln, Germany, 50937
        • Universitaetsklinikum Koeln; Innere Medizin I, Haematologie
  • Hong Kong
      • Hong Kong, Hong Kong
        • The University of Hong Kong
      • Hong Kong, Hong Kong
        • Princess Margaret Hospital
      • Kowloon, Hong Kong
        • Queen Elizabeth Hospital
      • Shatin, Hong Kong, 123456
        • The Chinese University of Hong Kong
  • Italy
    • Campania
      • Napoli, Campania, Italy, 80131
        • Seconda Università degli Studi di Napoli; Servizio Epato-Gastroenterologia
    • Lazio
      • Roma, Lazio, Italy, 128
        • Università Campus Bio-Medico di Roma; Oncologia Medica
    • Lombardia
      • Milano, Lombardia, Italy, 20133
        • Fondazione IRCCS Istituto Nazionale dei Tumori
      • Milano, Lombardia, Italy, 20162
        • Azienda Socio Sanitaria Territoriale Niguarda (Ospedale Niguarda Ca' Granda); Oncologico -Onc.Falck
    • Toscana
      • Pisa, Toscana, Italy, 56126
        • Azienda Ospedaliero Universitaria Pisana; Uff. Sperim. Clin. U.O. Farmaceutica
    • Umbria
      • Perugia, Umbria, Italy, 6132
        • Azienda Ospedaliera di Perugia Ospedale S. Maria della Misericordia ; S.C. Oncologia Medica
    • Veneto
      • Padova, Veneto, Italy, 35128
        • IOV - Istituto Oncologico Veneto - IRCCS; Oncologia Medica II
  • Japan
      • Aichi, Japan, 464-8681
        • Aichi Cancer Center Hospital; Respiratory Medicine
      • Ehime, Japan, 791-0280
        • NHO Shikoku Cancer Center; Dept of Respiratory Medicine
      • Fukuoka, Japan, 811-1395
        • NHO Kyushu Cancer Center
      • Hyogo, Japan, 673-8558
        • Hyogo Cancer Center, Dept of Respiratory Medicine
      • Kashiwa-shi, Japan, 277-8577
        • National Cancer Center Hospital; Dept of Respiratory Medicine
      • Miyagi, Japan, 981-1293
        • Miyagi Cancer Center; Respiratory Medicine
      • Niigata, Japan, 951-8566
        • Niigata Cancer Center Hospital; Internal Medicine
      • Osaka, Japan, 589-8511
        • Kindai University Hospital; Medical Oncology
      • Osaka, Japan, 534-0021
        • OSAKA CITY GENERAL HOSPITAL;Medical Oncology
      • Shizuoka, Japan, 411-8777
        • Shizuoka Cancer Center; Respiratory Internal Medicine
  • Korea, Republic of
      • Seoul, Korea, Republic of, 03080
        • Seoul National University Hospital
      • Seoul, Korea, Republic of, 03722
        • Severance Hospital, Yonsei University Health System
      • Seoul, Korea, Republic of, 06351
        • Samsung Medical Center
      • Seoul, Korea, Republic of, 5505
        • Asan Medical Center.
  • Netherlands
      • Amsterdam, Netherlands, 1066 CX
        • NKI The Netherlands Cancer Institute
      • Leiden, Netherlands, 2333 ZA
        • Leids Universitair Medisch Centrum
  • Poland
      • Gdansk, Poland, 80-214
        • Uniwersyteckie Centrum Kliniczne; Klinika Onkologii i Radioterapii
      • Gliwice, Poland, 44-101
        • Centrum Onkologii-Instytut im.M.Sklodowskiej Curie; Dept of Nuclear Med. and Endocrine Oncology
      • Pozna?, Poland, 60-569
        • Szpital Kliniczny Przemienienia Panskiego Uni. Medycznego im. Karola Marcinkowskiego; Chemotherapy
      • Warszawa, Poland, 02-781
        • Centrum Onkologii Instytut im. M. Sklodowskiej-Curie, Klinika Nowotworow Ukladu Chlonnego
  • Singapore
      • Singapore, Singapore, 169610
        • National Cancer Centre
      • Singapore, Singapore, 119074
        • National University Hospital; Haematology/Oncology
  • Spain
      • Barcelona, Spain, 08035
        • Vall d?Hebron Institute of Oncology (VHIO), Barcelona
      • Madrid, Spain, 28041
        • Hospital Universitario 12 de Octubre; Servicio de Oncologia
      • Madrid, Spain, 28040
        • Hospital Universitario Clínico San Carlos; Servicio de Oncologia
      • Madrid, Spain, 28046
        • Hospital Universitario La Paz; Servicio de Oncologia
      • Madrid, Spain, 28034
        • Hospital Universitario Ramon y Cajal; Servicio de Farmacia
      • Malaga, Spain, 29010
        • Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia
      • Sevilla, Spain, 41013
        • Hospital Universitario Virgen del Rocio; Servicio de Oncologia
    • Madrid
      • Fuenlabrada, Madrid, Spain, 28942
        • Centro Nacional de Investigaciones Oncológicas(CNIO); Gastrointestinal Cancer Clinical Research Unit
  • Taiwan
      • Tainan, Taiwan, 70457
        • National Cheng Kung University Hospital
      • Taipei, Taiwan, 10002
        • National Taiwan University Hospital
      • Taipei City, Taiwan, 11217
        • Taipei Veterans General Hospital
  • United Kingdom
      • Cambridge, United Kingdom, CB2 0QQ
        • Addenbrookes Hospital
      • London, United Kingdom, W1G 6AD
        • Sarah Cannon Research Institute
      • Manchester, United Kingdom, M2O 4BX
        • Christie Hospital Nhs Trust; Medical Oncology
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85013
        • Dignity Health St Joseph's Hospital and Medical Center
      • Scottsdale, Arizona, United States, 85259
        • Mayo Clinic
    • California
      • Duarte, California, United States, 91010
        • City of Hope Cancer Center; Division of Medical Oncology & Experimental Therapeutics
      • La Jolla, California, United States, 92037
        • Scripps Clinic
      • La Jolla, California, United States, 92093
        • University of California San Diego Moores Cancer Center; Dept of Lung Cancer
      • Los Angeles, California, United States, 90033
        • University of Southern California Medical Center
      • Orange, California, United States, 92868
        • Univ Of California Irvine College Of Medicine; 300194620
      • San Diego, California, United States, 92108
        • Southern California Kaiser Permanente
      • San Francisco, California, United States, 94115
        • UCSF Mount Zion Medical Ctr
      • Santa Monica, California, United States, 90403
        • Sarcoma Oncology Center
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Cancer Center
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Yale University
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Georgetown University Medical Center Lombardi Cancer Center
    • Florida
      • Sarasota, Florida, United States, 34232
        • Florida Cancer Specialists - Sarasota
      • Tampa, Florida, United States, 33612
        • H. Lee Moffitt Cancer Center and Research Inst.
    • Georgia
      • Athens, Georgia, United States, 30607
        • University Cancer & Blood Center, LLC; Research
      • Atlanta, Georgia, United States, 30322
        • Winship Cancer Institute
      • Newnan, Georgia, United States, 30265
        • Southeastern Regional Medical Center, Inc.
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University
      • Park Ridge, Illinois, United States, 60068
        • Advocate Medical Group - Park Ridge, Luther Lane - Oncology
      • Zion, Illinois, United States, 60099
        • Midwestern Regional Medical Center
    • Maryland
      • Baltimore, Maryland, United States, 21237
        • Weinberg Cancer Institution at Franklin Square
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
      • Boston, Massachusetts, United States, 02215
        • Dana Farber Cancer Institute
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan Comprehensive Cancer Center; Clinical Trials Office
      • Detroit, Michigan, United States, 48202
        • Henry Ford Hospital
      • Detroit, Michigan, United States, 48201
        • Karmanos Cancer Center
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Regents of the University of Minnesota
    • Missouri
      • Saint Louis, Missouri, United States, 63128
        • Washington University
    • Nevada
      • Las Vegas, Nevada, United States, 89169
        • Comprehensive Cancer Centers of Nevada (CCCN) - Central Valley
    • New York
      • East Setauket, New York, United States, 11733
        • North Shore Hem Onc Associates
      • New York, New York, United States, 11101
        • Memorial Sloan Kettering Cancer Center
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
        • Levine Cancer Institute
      • Durham, North Carolina, United States, 27710
        • Duke Cancer Institute
    • Ohio
      • Columbus, Ohio, United States, 43210
        • OSU, James Cancer Hospital
    • Oklahoma
      • Tulsa, Oklahoma, United States, 74133
        • Cancer Treatment Centers of America; Tulsa
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health & Science Univ
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19124
        • Cancer Treatment Centers of America - Eastern Regional Medical Center
    • Texas
      • Dallas, Texas, United States, 75230
        • Mary Crowley Medical Research Center
      • Houston, Texas, United States, 77030
        • University of Texas MD Anderson Cancer Center
      • Temple, Texas, United States, 76502
        • Baylor Scott & White Health
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • University of Utah Hospitals & Clinics
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Virginia Cancer Specialists, PC
      • Hampton, Virginia, United States, 23666
        • Virginia Oncology Associates - Hampton
    • Washington
      • Seattle, Washington, United States, 98195
        • University of Washington Seattle Cancer Care Alliance

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Histologically- or cytologically-confirmed diagnosis of locally advanced or metastatic solid tumor that harbors an NTRK1/2/3, ROS1, or ALK gene rearrangement
  • For patients enrolled via local molecular testing, an archival or fresh tumor tissue (unless medically contraindicated) is required to be submitted for independent central molecular testing at Ignyta's CLIA laboratory post-enrollment
  • Measurable or evaluable disease
  • Patients with CNS involvement, including leptomeningeal carcinomatosis, which is either asymptomatic or previously-treated and controlled, are allowed

  • Prior anticancer therapy is allowed (excluding approved or investigational Trk, ROS1, or ALK inhibitors in patients who have tumors that harbor those respective gene rearrangements)

    - Note: prior treatment with crizotinib is permitted only in ALK- or ROS1-rearranged NSCLC patients presenting with CNS-only progression. Other ALK inhibitors are prohibited.

  • At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed after prior chemotherapy or small molecule targeted therapy
  • At least 4 weeks must have elapsed since completion of antibody-directed therapy
  • Prior radiotherapy is allowed if more than 14 days have elapsed since the end of treatment
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 and minimum life expectancy of 4 weeks
  • Adequate organ function as defined per protocol
  • Ability to swallow entrectinib intact
  • Other protocol specified criteria

Exclusion Criteria:

  • Current participation in another therapeutic clinical trial

  • Prior treatment with approved or investigational Trk, ROS1, or ALK inhibitors in patients who have tumors that harbor those respective gene rearrangements

    - Note: prior treatment with crizotinib is permitted only in ALK- or ROS1-rearranged NSCLC patients presenting with CNS-only progression. Other ALK inhibitors are prohibited.

  • History of other previous cancer that would interfere with the determination of safety or efficacy
  • Familial or personal history of congenital bone disorders, or bone metabolism alterations
  • Incomplete recovery from any surgery
  • History of recent (within the past 3 months) symptomatic congestive heart failure or ejection fraction ≤50% observed during screening for the study
  • History of non-pharmacologically induced prolonged QTc interval
  • History of additional risk factors for torsades de pointes
  • Peripheral neuropathy Grade ≥ 2
  • Known active infections
  • Active gastrointestinal disease or other malabsorption syndromes
  • Known interstitial lung disease, interstitial fibrosis, or history of tyrosine kinase inhibitor-induced pneumonitis
  • Other protocol specified criteria

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: NTRK1/2/3-rearranged NSCLC
Oral entrectinib (RXDX-101)
Drug: Entrectinib
TrkA/B/C, ROS1, and ALK inhibitor
Other Names:
  • RXDX-101
Experimental: ROS1-rearranged NSCLC
Oral entrectinib (RXDX-101)
Drug: Entrectinib
TrkA/B/C, ROS1, and ALK inhibitor
Other Names:
  • RXDX-101
Experimental: ALK- or ROS1-rearranged NSCLC

with CNS-only progression previously treated with crizotinib (NOTE: The ALK-rearranged portion of this arm is now closed to enrollment.)

Oral entrectinib (RXDX-101)
Drug: Entrectinib
TrkA/B/C, ROS1, and ALK inhibitor
Other Names:
  • RXDX-101
Experimental: NTRK/1/2/3-rearranged mCRC
Oral entrectinib (RXDX-101)
Drug: Entrectinib
TrkA/B/C, ROS1, and ALK inhibitor
Other Names:
  • RXDX-101
Experimental: ROS1-rearranged mCRC
Oral entrectinib (RXDX-101)
Drug: Entrectinib
TrkA/B/C, ROS1, and ALK inhibitor
Other Names:
  • RXDX-101
Experimental: ALK-rearranged mCRC
Oral entrectinib (RXDX-101)
Drug: Entrectinib
TrkA/B/C, ROS1, and ALK inhibitor
Other Names:
  • RXDX-101
Experimental: NTRK1/2/3-rearranged other solid tumor
Oral entrectinib (RXDX-101)
Drug: Entrectinib
TrkA/B/C, ROS1, and ALK inhibitor
Other Names:
  • RXDX-101
Experimental: ROS1-rearranged other solid tumor
Oral entrectinib (RXDX-101)
Drug: Entrectinib
TrkA/B/C, ROS1, and ALK inhibitor
Other Names:
  • RXDX-101
Experimental: ALK-rearranged other solid tumor
Oral entrectinib (RXDX-101)
Drug: Entrectinib
TrkA/B/C, ROS1, and ALK inhibitor
Other Names:
  • RXDX-101

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate
Time Frame: Approximately 24 months
Assessed by blinded independent central review (BICR) using RECIST v1.1
Approximately 24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of Response
Time Frame: Approximately 24 months
Assessed by blinded independent central review (BICR) using RECIST v1.1
Approximately 24 months
Time to Response
Time Frame: Approximately 24 months
Assessed by blinded independent central review (BICR) using RECIST v1.1
Approximately 24 months
Clinical Benefit Rate
Time Frame: Approximately 24 months
Assessed by blinded independent central review (BICR) using RECIST v1.1
Approximately 24 months
Intracranial Tumor Response
Time Frame: Approximately 24 months
Assessed by blinded independent central review (BICR) using RANO or RANO-BM, as applicable
Approximately 24 months
CNS Progression-free Survival
Time Frame: Approximately 24 months
Assessed by blinded independent central review (BICR) using RANO or RANO-BM, as applicable
Approximately 24 months
Progression-free Survival
Time Frame: Approximately 30 months
Assessed by Kaplan-Meier method
Approximately 30 months
Overall Survival
Time Frame: Approximately 36 months
Assessed by Kaplan-Meier method
Approximately 36 months
Population PK
Time Frame: Approximately 24 months
Assessed by Kaplan-Meier method
Approximately 24 months
Adverse Events
Time Frame: Approximately 36 months
Type, incidence, severity, timing, seriousness, and relatedness of adverse events and laboratory abnormalities, graded by the NCI CTCAE
Approximately 36 months
Quality of Life
Time Frame: Approximately 24 months
Assessed with the European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30) and the Euro-QoL Group EQ-5D. NSCLC and mCRC patients will complete the lung cancer and colorectal cancer specific modules, QLQ-LC13 and QLQ-CR29, respectively
Approximately 24 months
Bone Growth and Bone Mineral Density
Time Frame: Approximately 30 months
Assessed with DHA scans
Approximately 30 months
Bone Biomarkers
Time Frame: Approximately 30 months
Measured by blood
Approximately 30 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hoffmann-La Roche

Investigators

  • Study Director: Clinical Trials, Hoffmann-La Roche

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 19, 2015

Primary Completion (Estimated)

December 31, 2024

Study Completion (Estimated)

April 1, 2025

Study Registration Dates

First Submitted

October 2, 2015

First Submitted That Met QC Criteria

October 2, 2015

First Posted (Estimated)

October 5, 2015

Study Record Updates

Last Update Posted (Actual)

March 28, 2024

Last Update Submitted That Met QC Criteria

March 27, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RXDX-101-02
  • 2015-003385-84 (EudraCT Number)
  • GO40782 (Other Identifier: Hoffman-La Roche)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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