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)
- Conditions
- Pancreatic CancerAdult Solid TumorLymphoma, Large-Cell, AnaplasticPrimary Brain TumorsSarcomasBreast CancerNon-Small Cell Lung CancerOvarian CancerPapillary Thyroid CancerSalivary Gland Cancers
- Interventions
- Registration Number
- NCT02568267
- Lead Sponsor
- Hoffmann-La Roche
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 534
-
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
-
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
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Familial or personal history of congenital bone disorders, or bone metabolism alterations
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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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description NTRK1/2/3-rearranged NSCLC Entrectinib Oral entrectinib (RXDX-101) ALK-rearranged mCRC Entrectinib Oral entrectinib (RXDX-101) ALK- or ROS1-rearranged NSCLC Entrectinib 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) ROS1-rearranged NSCLC Entrectinib Oral entrectinib (RXDX-101) NTRK/1/2/3-rearranged mCRC Entrectinib Oral entrectinib (RXDX-101) ROS1-rearranged mCRC Entrectinib Oral entrectinib (RXDX-101) NTRK1/2/3-rearranged other solid tumor Entrectinib Oral entrectinib (RXDX-101) ROS1-rearranged other solid tumor Entrectinib Oral entrectinib (RXDX-101) ALK-rearranged other solid tumor Entrectinib Oral entrectinib (RXDX-101)
- Primary Outcome Measures
Name Time Method Objective Response Rate Approximately 24 months Assessed by blinded independent central review (BICR) using RECIST v1.1
- Secondary Outcome Measures
Name Time Method Clinical Benefit Rate Approximately 24 months Assessed by blinded independent central review (BICR) using RECIST v1.1
Progression-free Survival Approximately 30 months Assessed by Kaplan-Meier method
Duration of Response Approximately 24 months Assessed by blinded independent central review (BICR) using RECIST v1.1
Time to Response Approximately 24 months Assessed by blinded independent central review (BICR) using RECIST v1.1
Intracranial Tumor Response Approximately 24 months Assessed by blinded independent central review (BICR) using RANO or RANO-BM, as applicable
Overall Survival Approximately 36 months Assessed by Kaplan-Meier method
Population PK Approximately 24 months Assessed by Kaplan-Meier method
Bone Biomarkers Approximately 30 months Measured by blood
CNS Progression-free Survival Approximately 24 months Assessed by blinded independent central review (BICR) using RANO or RANO-BM, as applicable
Bone Growth and Bone Mineral Density Approximately 30 months Assessed with DHA scans
Adverse Events Approximately 36 months Type, incidence, severity, timing, seriousness, and relatedness of adverse events and laboratory abnormalities, graded by the NCI CTCAE
Quality of Life 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
Trial Locations
- Locations (122)
Dignity Health St Joseph's Hospital and Medical Center
🇺🇸Phoenix, Arizona, United States
Mayo Clinic
🇺🇸Phoenix, Arizona, United States
City of Hope Cancer Center
🇺🇸Duarte, California, United States
Scripps Clinic
🇺🇸La Jolla, California, United States
University of California San Diego Moores Cancer Center
🇺🇸La Jolla, California, United States
Southern California Kaiser Permanente
🇺🇸Los Angeles, California, United States
University of Southern California Medical Center
🇺🇸Los Angeles, California, United States
Univ Of California Irvine College Of Medicine
🇺🇸Orange, California, United States
UCSF Mount Zion Medical Ctr
🇺🇸San Francisco, California, United States
Sarcoma Oncology Center
🇺🇸Santa Monica, California, United States
University of Colorado Cancer Center
🇺🇸Aurora, Colorado, United States
Yale University
🇺🇸New Haven, Connecticut, United States
Georgetown University Medical Center Lombardi Cancer Center
🇺🇸Washington, District of Columbia, United States
Florida Cancer Specialists - Sarasota
🇺🇸Sarasota, Florida, United States
H. Lee Moffitt Cancer Center and Research Inst.
🇺🇸Tampa, Florida, United States
University Cancer & Blood Center, LLC
🇺🇸Athens, Georgia, United States
Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
Southeastern Regional Medical Center, Inc.
🇺🇸Newnan, Georgia, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Advocate Medical Group - Park Ridge, Luther Lane - Oncology
🇺🇸Park Ridge, Illinois, United States
Midwestern Regional Medical Center
🇺🇸Zion, Illinois, United States
Weinberg Cancer Institution at Franklin Square
🇺🇸Baltimore, Maryland, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
University of Michigan Comprehensive Cancer Center
🇺🇸Ann Arbor, Michigan, United States
Karmanos Cancer Center
🇺🇸Detroit, Michigan, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Regents of the University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
Comprehensive Cancer Centers of Nevada (CCCN) - Central Valley
🇺🇸Las Vegas, Nevada, United States
North Shore Hem Onc Associates
🇺🇸East Setauket, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
Duke Cancer Institute
🇺🇸Durham, North Carolina, United States
OSU, James Cancer Hospital
🇺🇸Columbus, Ohio, United States
Cancer Treatment Centers of America
🇺🇸Tulsa, Oklahoma, United States
Oregon Health & Science Univ
🇺🇸Portland, Oregon, United States
Mary Crowley Medical Research Center
🇺🇸Dallas, Texas, United States
University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Baylor Scott & White Health
🇺🇸Temple, Texas, United States
University of Utah Hospitals & Clinics
🇺🇸Salt Lake City, Utah, United States
Virginia Cancer Specialists, PC
🇺🇸Fairfax, Virginia, United States
Virginia Oncology Associates - Hampton
🇺🇸Norfolk, Virginia, United States
University of Washington Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
Liverpool Hospital
🇦🇺Liverpool, New South Wales, Australia
Newcastle Private Hospital
🇦🇺Newcastle, New South Wales, Australia
Flinders Medical Centre
🇦🇺Bedford Park, South Australia, Australia
Austin Health
🇦🇺Heidelberg, Victoria, Australia
Antwerp University Hospital
🇧🇪Edegem, Belgium
Beijing Cancer Hospital
🇨🇳Beijing, China
Sichuan Provincial Cancer Hospital
🇨🇳Chengdu, China
Cancer Center of Guangzhou Medical University
🇨🇳Guangzhou, China
Zhejiang Cancer Hospital
🇨🇳Hangzhou, China
Harbin Medical University Cancer Hospital
🇨🇳Harbin, China
Shanghai chest hospital
🇨🇳Shanghai, China
Fudan University Shanghai Cancer Center
🇨🇳Shanghai, 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
Institut de Cancerologie de l Ouest
🇫🇷Angers, France
Institut Bergonie
🇫🇷Bordeaux, France
Centre Leon Berard
🇫🇷Lyon, France
Hôpital Nord - AP-HM Marseille#
🇫🇷Marseille cedex 20, France
Hôpital de la Timone
🇫🇷Marseille cedex 5, France
Institut de Recherche en Cancérologie de Montpellier
🇫🇷Montpellier, France
Institut Curie
🇫🇷Paris, France
Institut De Cancerologie De L'ouest - Rene Gauducheau - Biology
🇫🇷Saint Herblain, France
Institut Claudius Regaud
🇫🇷Toulouse, France
Institut Gustave Roussy
🇫🇷Villejuif cedex, France
Evang. Lungenklinik Berlin Klinik für Pneumologie
🇩🇪Berlin, Germany
Universitaetsklinikum Carl Gustav Carus TU Dresden
🇩🇪Dresden, Germany
Universitaetsmedizin Goettingen
🇩🇪Göttingen, Germany
NCT Uniklinikum Heidelberg
🇩🇪Heidelberg, Germany
Universitaetsklinikum Koeln
🇩🇪Köln, Germany
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, Hong Kong
Seconda Università degli Studi di Napoli
🇮🇹Napoli, Campania, Italy
Università Campus Bio-Medico di Roma
🇮🇹Roma, Lazio, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
🇮🇹Milano, Lombardia, Italy
Azienda Socio Sanitaria Territoriale Niguarda (Ospedale Niguarda Ca' Granda)
🇮🇹Milano, Lombardia, Italy
Azienda Ospedaliero Universitaria Pisana
🇮🇹Pisa, Toscana, Italy
Azienda Ospedaliera di Perugia Ospedale S. Maria della Misericordia
🇮🇹Perugia, Umbria, Italy
IOV - Istituto Oncologico Veneto - IRCCS
🇮🇹Padova, Veneto, Italy
Aichi Cancer Center Hospital
🇯🇵Aichi, Japan
National Cancer Center Hospital
🇯🇵Kashiwa-shi, Japan
NHO Kyushu Cancer Center
🇯🇵Fukuoka, Japan
Hyogo Cancer Center, Dept of Respiratory Medicine
🇯🇵Hyogo, Japan
NHO Shikoku Cancer Center
🇯🇵Matsuyama-shi, Japan
Miyagi Cancer Center
🇯🇵Miyagi, Japan
Niigata Cancer Center Hospital
🇯🇵Niigata, Japan
Osaka City General Hospital
🇯🇵Osaka, Japan
Kindai University Hospital
🇯🇵Osaka, Japan
Shizuoka Cancer Center
🇯🇵Shizuoka, Japan
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Asan Medical Center.
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
NKI The Netherlands Cancer Institute
🇳🇱Amsterdam, Netherlands
Leids Universitair Medisch Centrum
🇳🇱Leiden, Netherlands
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdansk, Poland
Centrum Onkologii-Instytut im.M.Sklodowskiej Curie
🇵🇱Gliwice, Poland
Szpital Kliniczny Przemienienia Panskiego Uni. Medycznego im. Karola Marcinkowskiego
🇵🇱Pozna?, Poland
Centrum Onkologii Instytut im. M. Sklodowskiej-Curie, Klinika Nowotworow Ukladu Chlonnego
🇵🇱Warszawa, Poland
National University Hospital
🇸🇬Singapore, Singapore
National Cancer Centre
🇸🇬Singapore, Singapore
Centro Nacional de Investigaciones Oncológicas(CNIO)
🇪🇸Fuenlabrada, Madrid, Spain
Vall d?Hebron Institute of Oncology (VHIO), Barcelona
🇪🇸Barcelona, Spain
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
Hospital Universitario Clínico San Carlos
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Clinico Universitario Virgen de la Victoria
🇪🇸Malaga, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
Addenbrookes Hospital
🇬🇧Cambridge, United Kingdom
Sarah Cannon Research Institute
🇬🇧London, United Kingdom
The Christie
🇬🇧Manchester, United Kingdom