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)

Breast Cancer Clinical Trial

— STARTRK-2  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02568267
• Other study ID #: RXDX-101-02
• Secondary ID: 2015-003385-84GO
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: November 19, 2015
• Est. completion date: April 1, 2025

Study information

• Verified date: March 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 534
• Est. completion date: April 1, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adult Solid Tumor
• Brain Neoplasms
• Breast Cancer
• Carcinoma, Non-Small-Cell Lung
• Cholangiocarcinoma
• Colorectal Cancer
• Colorectal Neoplasms
• Head and Neck Neoplasms
• Lymphoma, Large-Cell, Anaplastic
• Melanoma
• Neoplasms
• Neuroendocrine Tumors
• Non-Small Cell Lung Cancer
• Ovarian Cancer
• Ovarian Neoplasms
• Pancreatic Cancer
• Pancreatic Neoplasms
• Papillary Thyroid Cancer
• Primary Brain Tumors
• Renal Cell Carcinoma
• Salivary Gland Cancers
• Salivary Gland Neoplasms
• Sarcoma
• Sarcomas
• Thyroid Cancer, Papillary
• Thyroid Neoplasms

Intervention

Drug:
• Entrectinib
TrkA/B/C, ROS1, and ALK inhibitor

Locations

Country	Name	City	State
Australia	Flinders Medical Centre	Bedford Park	South Australia
Australia	Austin Health	Heidelberg	Victoria
Australia	Liverpool Hospital	Liverpool	New South Wales
Australia	Newcastle Private Hospital	New Lambton Heights	New South Wales
Belgium	Antwerp University Hospital	Edegem
China	Beijing Cancer Hospital	Beijing
China	Sichuan Provincial Cancer Hospital	Chengdu
China	Cancer Center of Guangzhou Medical University	Guangzhou
China	Harbin Medical University Cancer Hospital	Harbin
China	Shanghai chest hospital	Shanghai
China	Fudan University Shanghai Cancer Center	Shanghai City
China	Shenzhen People's Hospital	Shenzhen
China	Tianjin Cancer Hospital	Tianjin
China	Union Hospital Tongji Medical College Huazhong University of Science and Technology	Wuhan City
China	Zhejiang Cancer Hospital	Zhejiang
France	Institut de Cancerologie de l Ouest	Angers
France	Institut Bergonie; Oncologie	Bordeaux
France	Centre Leon Berard; Departement Oncologie Medicale	Lyon
France	Hôpital Nord - AP-HM Marseille#; Service d'Oncologie Multidisciplinaire	Marseille
France	Hôpital de la Timone; Oncologie Médicale Hématologie & Soins Palliatifs	Marseille cedex 5
France	Institut de Recherche en Cancérologie de Montpellier	Montpellier cedex 5
France	Institut Curie; Oncologie Medicale	Paris
France	Institut De Cancerologie De L'ouest - Rene Gauducheau - Biology	Saint Herblain
France	Institut Claudius Regaud; Departement Oncologie Medicale	Toulouse
France	Institut Gustave Roussy; Pathologie Thoracique	Villejuif cedex
Germany	Evang. Lungenklinik Berlin Klinik für Pneumologie	Berlin
Germany	Universitaetsklinikum Carl Gustav Carus TU Dresden	Dresden
Germany	Universitaetsmedizin Goettingen; Abteilung Haematologie und Onkologie	Göttingen
Germany	NCT Uniklinikum Heidelberg; Medizinische Onkologie	Heidelberg
Germany	Universitaetsklinikum Koeln; Innere Medizin I, Haematologie	Köln
Hong Kong	Princess Margaret Hospital	Hong Kong
Hong Kong	The University of Hong Kong	Hong Kong
Hong Kong	Queen Elizabeth Hospital	Kowloon
Hong Kong	The Chinese University of Hong Kong	Shatin
Italy	Azienda Socio Sanitaria Territoriale Niguarda (Ospedale Niguarda Ca' Granda); Oncologico -Onc.Falck	Milano	Lombardia
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano	Lombardia
Italy	Seconda Università degli Studi di Napoli; Servizio Epato-Gastroenterologia	Napoli	Campania
Italy	IOV - Istituto Oncologico Veneto - IRCCS; Oncologia Medica II	Padova	Veneto
Italy	Azienda Ospedaliera di Perugia Ospedale S. Maria della Misericordia ; S.C. Oncologia Medica	Perugia	Umbria
Italy	Azienda Ospedaliero Universitaria Pisana; Uff. Sperim. Clin. U.O. Farmaceutica	Pisa	Toscana
Italy	Università Campus Bio-Medico di Roma; Oncologia Medica	Roma	Lazio
Japan	Aichi Cancer Center Hospital; Respiratory Medicine	Aichi
Japan	NHO Shikoku Cancer Center; Dept of Respiratory Medicine	Ehime
Japan	NHO Kyushu Cancer Center	Fukuoka
Japan	Hyogo Cancer Center, Dept of Respiratory Medicine	Hyogo
Japan	National Cancer Center Hospital; Dept of Respiratory Medicine	Kashiwa-shi
Japan	Miyagi Cancer Center; Respiratory Medicine	Miyagi
Japan	Niigata Cancer Center Hospital; Internal Medicine	Niigata
Japan	Kindai University Hospital; Medical Oncology	Osaka
Japan	OSAKA CITY GENERAL HOSPITAL;Medical Oncology	Osaka
Japan	Shizuoka Cancer Center; Respiratory Internal Medicine	Shizuoka
Korea, Republic of	Asan Medical Center.	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Netherlands	NKI The Netherlands Cancer Institute	Amsterdam
Netherlands	Leids Universitair Medisch Centrum	Leiden
Poland	Uniwersyteckie Centrum Kliniczne; Klinika Onkologii i Radioterapii	Gdansk
Poland	Centrum Onkologii-Instytut im.M.Sklodowskiej Curie; Dept of Nuclear Med. and Endocrine Oncology	Gliwice
Poland	Szpital Kliniczny Przemienienia Panskiego Uni. Medycznego im. Karola Marcinkowskiego; Chemotherapy	Pozna?
Poland	Centrum Onkologii Instytut im. M. Sklodowskiej-Curie, Klinika Nowotworow Ukladu Chlonnego	Warszawa
Singapore	National Cancer Centre	Singapore
Singapore	National University Hospital; Haematology/Oncology	Singapore
Spain	Vall d?Hebron Institute of Oncology (VHIO), Barcelona	Barcelona
Spain	Centro Nacional de Investigaciones Oncológicas(CNIO); Gastrointestinal Cancer Clinical Research Unit	Fuenlabrada	Madrid
Spain	Hospital Universitario 12 de Octubre; Servicio de Oncologia	Madrid
Spain	Hospital Universitario Clínico San Carlos; Servicio de Oncologia	Madrid
Spain	Hospital Universitario La Paz; Servicio de Oncologia	Madrid
Spain	Hospital Universitario Ramon y Cajal; Servicio de Farmacia	Madrid
Spain	Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia	Malaga
Spain	Hospital Universitario Virgen del Rocio; Servicio de Oncologia	Sevilla
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei City
United Kingdom	Addenbrookes Hospital	Cambridge
United Kingdom	Sarah Cannon Research Institute	London
United Kingdom	Christie Hospital Nhs Trust; Medical Oncology	Manchester
United States	University of Michigan Comprehensive Cancer Center; Clinical Trials Office	Ann Arbor	Michigan
United States	University Cancer & Blood Center, LLC; Research	Athens	Georgia
United States	Winship Cancer Institute	Atlanta	Georgia
United States	University of Colorado Cancer Center	Aurora	Colorado
United States	Weinberg Cancer Institution at Franklin Square	Baltimore	Maryland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	Northwestern University	Chicago	Illinois
United States	OSU, James Cancer Hospital	Columbus	Ohio
United States	Mary Crowley Medical Research Center	Dallas	Texas
United States	Henry Ford Hospital	Detroit	Michigan
United States	Karmanos Cancer Center	Detroit	Michigan
United States	City of Hope Cancer Center; Division of Medical Oncology & Experimental Therapeutics	Duarte	California
United States	Duke Cancer Institute	Durham	North Carolina
United States	North Shore Hem Onc Associates	East Setauket	New York
United States	Virginia Cancer Specialists, PC	Fairfax	Virginia
United States	Virginia Oncology Associates - Hampton	Hampton	Virginia
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Scripps Clinic	La Jolla	California
United States	University of California San Diego Moores Cancer Center; Dept of Lung Cancer	La Jolla	California
United States	Comprehensive Cancer Centers of Nevada (CCCN) - Central Valley	Las Vegas	Nevada
United States	University of Southern California Medical Center	Los Angeles	California
United States	Regents of the University of Minnesota	Minneapolis	Minnesota
United States	Yale University	New Haven	Connecticut
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Southeastern Regional Medical Center, Inc.	Newnan	Georgia
United States	Univ Of California Irvine College Of Medicine; 300194620	Orange	California
United States	Advocate Medical Group - Park Ridge, Luther Lane - Oncology	Park Ridge	Illinois
United States	Cancer Treatment Centers of America - Eastern Regional Medical Center	Philadelphia	Pennsylvania
United States	Dignity Health St Joseph's Hospital and Medical Center	Phoenix	Arizona
United States	Oregon Health & Science Univ	Portland	Oregon
United States	Washington University	Saint Louis	Missouri
United States	University of Utah Hospitals & Clinics	Salt Lake City	Utah
United States	Southern California Kaiser Permanente	San Diego	California
United States	UCSF Mount Zion Medical Ctr	San Francisco	California
United States	Sarcoma Oncology Center	Santa Monica	California
United States	Florida Cancer Specialists - Sarasota	Sarasota	Florida
United States	Mayo Clinic	Scottsdale	Arizona
United States	University of Washington Seattle Cancer Care Alliance	Seattle	Washington
United States	H. Lee Moffitt Cancer Center and Research Inst.	Tampa	Florida
United States	Baylor Scott & White Health	Temple	Texas
United States	Cancer Treatment Centers of America; Tulsa	Tulsa	Oklahoma
United States	Georgetown University Medical Center Lombardi Cancer Center	Washington	District of Columbia
United States	Midwestern Regional Medical Center	Zion	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  China,  France,  Germany,  Hong Kong,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Poland,  Singapore,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate	Assessed by blinded independent central review (BICR) using RECIST v1.1	Approximately 24 months
Secondary	Duration of Response	Assessed by blinded independent central review (BICR) using RECIST v1.1	Approximately 24 months
Secondary	Time to Response	Assessed by blinded independent central review (BICR) using RECIST v1.1	Approximately 24 months
Secondary	Clinical Benefit Rate	Assessed by blinded independent central review (BICR) using RECIST v1.1	Approximately 24 months
Secondary	Intracranial Tumor Response	Assessed by blinded independent central review (BICR) using RANO or RANO-BM, as applicable	Approximately 24 months
Secondary	CNS Progression-free Survival	Assessed by blinded independent central review (BICR) using RANO or RANO-BM, as applicable	Approximately 24 months
Secondary	Progression-free Survival	Assessed by Kaplan-Meier method	Approximately 30 months
Secondary	Overall Survival	Assessed by Kaplan-Meier method	Approximately 36 months
Secondary	Population PK	Assessed by Kaplan-Meier method	Approximately 24 months
Secondary	Adverse Events	Type, incidence, severity, timing, seriousness, and relatedness of adverse events and laboratory abnormalities, graded by the NCI CTCAE	Approximately 36 months
Secondary	Quality of Life	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
Secondary	Bone Growth and Bone Mineral Density	Assessed with DHA scans	Approximately 30 months
Secondary	Bone Biomarkers	Measured by blood	Approximately 30 months