Clinical Trial - NCT02568267

       

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)

Recruiting

Sponsor: Hoffmann-La Roche

Collaborators:

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT02568267

Protocol Info

Short Description: Phase 2 Entrectinib for ASTs with NTRK1/2/3, ROS1, or ALK
Long Description: 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 (STARTRK-2)
MGH Status: Open
Sponsor: Ignyta Operating, Inc.
Disease Program: Phase I

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.




Purpose

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.
Condition Title Intervention Phase
Breast Cancer Cholangiocarcinoma Colorectal Cancer Head and Neck Neoplasms Lymphoma, Large-Cell, Anaplastic Melanoma Neuroendocrine Tumors Non-Small Cell Lung Cancer Ovarian Cancer Pancreatic Cancer Papillary Thyroid Cancer Primary Brain Tumors Renal Cell Carcinoma Sarcomas Salivary Gland Cancers Adult Solid Tumor Entrectinib Phase 2
Study Type Interventional
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

Primary Outcome Measures

Objective Response Rate [Time Frame: Approximately 24 months] [Designated as safety issue: ]


Secondary Outcome Measures

Duration of Response [Time Frame: Approximately 24 months] [Designated as safety issue: ]

Time to Response [Time Frame: Approximately 24 months] [Designated as safety issue: ]

Clinical Benefit Rate [Time Frame: Approximately 24 months] [Designated as safety issue: ]

Intracranial Tumor Response [Time Frame: Approximately 24 months] [Designated as safety issue: ]

CNS Progression-free Survival [Time Frame: Approximately 24 months] [Designated as safety issue: ]

Progression-free Survival [Time Frame: Approximately 30 months] [Designated as safety issue: ]

Overall Survival [Time Frame: Approximately 36 months] [Designated as safety issue: ]

Population PK [Time Frame: Approximately 24 months] [Designated as safety issue: ]

Adverse Events [Time Frame: Approximately 36 months] [Designated as safety issue: ]

Quality of Life [Time Frame: Approximately 24 months] [Designated as safety issue: ]

Bone Growth and Bone Mineral Density [Time Frame: Approximately 30 months] [Designated as safety issue: ]

Bone Biomarkers [Time Frame: Approximately 30 months] [Designated as safety issue: ]

Estimated Enrollment: 500
Study Start Date: November 2015
Estimated Study Completion Date: December 2024
Estimated Primary Completion Date: December 2022
Arms Assigned Interventions

Experimental:NTRK1/2/3-rearranged NSCLC

Oral entrectinib (RXDX-101)

Experimental:ROS1-rearranged NSCLC

Oral entrectinib (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

Experimental:NTRK/1/2/3-rearranged mCRC

Oral entrectinib (RXDX-101)

Experimental:ROS1-rearranged mCRC

Oral entrectinib (RXDX-101)

Experimental:ALK-rearranged mCRC

Oral entrectinib (RXDX-101)

Experimental:NTRK1/2/3-rearranged other solid tumor

Oral entrectinib (RXDX-101)

Experimental:ROS1-rearranged other solid tumor

Oral entrectinib (RXDX-101)

Experimental:ALK-rearranged other solid tumor

Oral entrectinib (RXDX-101)

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

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
  • • Note: Patients diagnosed with anaplastic large cell lymphoma (ALCL) harboring a gene rearrangement of interest may be eligible provided they meet all other inclusion/exclusion criteria
  • • 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, bone metabolism alterations or osteopenia
  • • 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT02568267

Locations

  • United States, Arizona
    • Western Regional Medical Center at Cancer Treatment Centers of America Goodyear, Arizona, United States, 85338
    • Dignity Health St Joseph's Hospital and Medical Center Phoenix, Arizona, United States, 85013
    • Mayo Clinic Scottsdale, Arizona, United States, 85259
  • United States, California
    • City of Hope Cancer Center; Division of Medical Oncology & Experimental Therapeutics Duarte, California, United States, 91010
    • Scripps Clinic La Jolla, California, United States, 92037
    • University of California San Diego Moores Cancer Center; Dept of Lung Cancer La Jolla, California, United States, 92093
    • University of Southern California Medical Center Los Angeles, California, United States, 90033
    • Univ Of California Irvine College Of Medicine; 300194620 Orange, California, United States, 92868
    • Southern California Kaiser Permanente San Diego, California, United States, 92108
    • UCSF Mount Zion Medical Ctr San Francisco, California, United States, 94115
    • Sarcoma Oncology Center Santa Monica, California, United States, 90403
  • United States, Colorado
    • University of Colorado Cancer Center Aurora, Colorado, United States, 80045
  • United States, Connecticut
    • Yale University New Haven, Connecticut, United States, 06510
  • United States, District of Columbia
    • Georgetown University Medical Center Lombardi Cancer Center Washington, District of Columbia, United States, 20007
  • United States, Florida
    • Florida Cancer Specialists - Sarasota Sarasota, Florida, United States, 34232
    • H. Lee Moffitt Cancer Center and Research Inst. Tampa, Florida, United States, 33612
    • Cleveland Clinic Florida Weston, Florida, United States, 33331
  • United States, Georgia
    • University Cancer & Blood Center, LLC; Research Athens, Georgia, United States, 30607
    • Winship Cancer Institute Atlanta, Georgia, United States, 30322
    • Southeastern Regional Medical Center, Inc. Newnan, Georgia, United States, 30265
  • United States, Hawaii
    • University of Hawaii Cancer Center Honolulu, Hawaii, United States, 96813
  • United States, Illinois
    • Northwestern University Chicago, Illinois, United States, 60611
    • Advocate Medical Group - Park Ridge, Luther Lane - Oncology Park Ridge, Illinois, United States, 60068
    • Midwestern Regional Medical Center Zion, Illinois, United States, 60099
  • United States, Maryland
    • Weinberg Cancer Institution at Franklin Square Baltimore, Maryland, United States, 21237
  • United States, Massachusetts
    • Massachusetts General Hospital Boston, Massachusetts, United States, 02114
    • Beth Israel Deaconess Medical Center Boston, Massachusetts, United States, 02215
    • Dana Farber Cancer Institute Boston, Massachusetts, United States, 02215
  • United States, Michigan
    • University of Michigan Comprehensive Cancer Center Ann Arbor, Michigan, United States, 48109
    • Karmanos Cancer Center Detroit, Michigan, United States, 48201
    • Henry Ford Hospital Detroit, Michigan, United States, 48202
  • United States, Minnesota
    • Regents of the University of Minnesota Minneapolis, Minnesota, United States, 55455
  • United States, Missouri
    • Washington University Saint Louis, Missouri, United States, 63128
  • United States, Nevada
    • Comprehensive Cancer Centers of Nevada (CCCN) - Central Valley Las Vegas, Nevada, United States, 89169
  • United States, New Hampshire
    • Dartmouth Hitchcock Medical Center Lebanon, New Hampshire, United States, 03756
  • United States, New York
    • North Shore Hem Onc Associates East Setauket, New York, United States, 11733
    • Memorial Sloan Kettering Cancer Center New York, New York, United States, 10065
  • United States, North Carolina
    • Levine Cancer Institute Charlotte, North Carolina, United States, 28204
    • Duke Cancer Institute Durham, North Carolina, United States, 27710
  • United States, Ohio
    • Cleveland Clinic Cleveland, Ohio, United States, 44195
    • OSU, James Cancer Hospital Columbus, Ohio, United States, 43210
  • United States, Oklahoma
    • Cancer Treatment Centers of America; Tulsa Tulsa, Oklahoma, United States, 74133
  • United States, Oregon
    • Providence Portland Medical Center Portland, Oregon, United States, 97213
    • Oregon Health & Science Univ Portland, Oregon, United States, 97239
  • United States, Pennsylvania
    • Cancer Treatment Centers of America - Eastern Regional Medical Center Philadelphia, Pennsylvania, United States, 19124
  • United States, Texas
    • Mary Crowley Medical Research Center Dallas, Texas, United States, 75230
    • University Hospital Medical Oncology Clinic; Harold C. Simmons Comprehensive Cancer Center Dallas, Texas, United States, 75390
    • University of Texas MD Anderson Cancer Center Houston, Texas, United States, 77030
    • Baylor Scott & White Health Temple, Texas, United States, 76502
  • United States, Utah
    • University of Utah Hospitals & Clinics Salt Lake City, Utah, United States, 84132
  • United States, Virginia
    • Virginia Cancer Specialists, PC Fairfax, Virginia, United States, 22031
    • Virginia Oncology Associates - Hampton Hampton, Virginia, United States, 23666
  • United States, Washington
    • University of Washington Seattle Cancer Care Alliance Seattle, Washington, United States, 98195
  • United States, Wisconsin
    • Wheaton Franciscan Cancer Care-All Saints Franklin, Wisconsin, United States, 53132
  • Australia, New South Wales
    • Border Medical Oncology Research Unit Albury, New South Wales, Australia, 2640
    • Liverpool Hospital Liverpool, New South Wales, Australia, 2170
    • Newcastle Private Hospital New Lambton Heights, New South Wales, Australia, 2305
  • Australia, South Australia
    • Flinders Medical Centre Bedford Park, South Australia, Australia, 5042
  • Australia, Victoria
    • Austin Hospital Heidelberg, Victoria, Australia, 3084
  • Belgium,
    • Antwerp University Hospital Edegem, , Belgium, 2650
  • China,
    • Beijing Cancer Hospital Beijing, , China, 100142
    • Beijing Union Hospital Beijing, , China, 100730
    • Hunan Cancer Hospital Changsha City, , China, 410013
    • Sichuan Provincial Cancer Hospital Chengdu, , China, 610041
    • Fujian Provincial Cancer Hospital Fuzhou City, , China, 350014
    • Cancer Center of Guangzhou Medical University Guangzhou, , China, 510000
    • Harbin Medical University Cancer Hospital Harbin, , China, 150081
    • Shanghai chest hospital Shanghai, , China, 200030
    • Fudan University Shanghai Cancer Center Shanghai, , China, 200120
    • Shenzhen People's Hospital Shenzhen, , China, 510852
    • Tianjin Cancer Hospital Tianjin, , China, 300060
    • Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan City, , China, 430023
    • Zhejiang Cancer Hospital Zhejiang, , China, 310022
  • France,
    • Institut de Cancerologie de l Ouest Angers, , France, 49055
    • Institut Bergonie; Oncologie Bordeaux, , France, 33076
    • Centre Oscar Lambret; Chir Cancerologie General Lille, , France, 59000
    • Centre Leon Berard; Departement Oncologie Medicale Lyon, , France, 69373
    • Hôpital de la Timone; Oncologie Médicale Hématologie & Soins Palliatifs Marseille cedex 5, , France, 13385
    • Hôpital Nord - AP-HM Marseille#; Service d'Oncologie Multidisciplinaire Marseille, , France, 13015
    • Institut de Recherche en Cancérologie de Montpellier Montpellier cedex 5, , France, 34298
    • Hôpital Européen Georges Pompidou; Hématologie Oncologie Paris cedex 15, , France, 75908
    • Institut Curie; Oncologie Medicale Paris, , France, 75231
    • Institut De Cancerologie De L'ouest - Rene Gauducheau - Biology Saint Herblain, , France, 44805
    • Institut Claudius Regaud; Departement Oncologie Medicale Toulouse, , France, 31059
    • Institut Gustave Roussy; Pathologie Thoracique Villejuif cedex, , France, 94805
  • Germany,
    • Charite Universitaetsmedizin Berlin - Campus Charite Mitte ; Charite Comprehensive Cancer Center Berlin, , Germany, 10117
    • Evang. Lungenklinik Berlin Klinik für Pneumologie Berlin, , Germany, 13125
    • Universitaetsklinikum Carl Gustav Carus TU Dresden Dresden, , Germany, 01307
    • Asklepios-Fachkliniken Muenchen-Gauting; Onkologie Gauting, , Germany, 82131
    • Universitaetsmedizin Goettingen; Abteilung Haematologie und Onkologie Göttingen, , Germany, 37075
    • NCT Uniklinikum Heidelberg; Medizinische Onkologie Heidelberg, , Germany, 69120
    • Universitaetsklinikum Koeln; Innere Medizin I, Haematologie Köln, , Germany, 50937
  • Hong Kong,
    • Hong Kong Integrated Oncology Centre Hong Kong, , 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, , Hong Kong, 123456
  • Italy, Campania
    • Seconda Università degli Studi di Napoli; Servizio Epato-Gastroenterologia Napoli, Campania, Italy, 80131
  • Italy, Lazio
    • Università Campus Bio-Medico di Roma; Oncologia Medica Roma, Lazio, Italy, 128
  • Italy, Liguria
    • Azienda Ospedaliero Universitaria San Martino; Lung Cancer Unit Genova, Liguria, Italy, 16132
  • Italy, Lombardia
    • Fondazione IRCCS Istituto Nazionale dei Tumori Milano, Lombardia, Italy, 20133
    • Azienda Socio Sanitaria Territoriale Niguarda (Ospedale Niguarda Ca' Granda); Oncologico -Onc.Falck Milano, Lombardia, Italy, 20162
  • Italy, Piemonte
    • Fondazione del Piemonte per l'Oncologia - IRCCS;Ematologia Candiolo, Piemonte, Italy, 10060
    • Azienda Ospedaliero-Universitaria S.Luigi Gonzaga; SSD Oncologia Polmonare Orbassano, Piemonte, Italy, 10043
    • A.O Città della Salute e della Scienza di Torino; Colorectal Cancer Unit (CRCU) - SSCVD Torino, Piemonte, Italy, 10126
  • Italy, Toscana
    • Azienda Ospedaliero - Universitaria Pisana U.O. Oncologia Medica 2 Universitaria - Polo Oncologico Pisa, Toscana, Italy, 56126
  • Italy, Umbria
    • Azienda Ospedaliera di Perugia Ospedale S. Maria della Misericordia ; S.C. Oncologia Medica Perugia, Umbria, Italy, 6132
  • Italy, Veneto
    • IOV - Istituto Oncologico Veneto - IRCCS; Oncologia Medica II Padova, Veneto, Italy, 35128
  • Japan,
    • Aichi Cancer Center Hospital; Respiratory Medicine Aichi, , Japan, 464-8681
    • NHO Shikoku Cancer Center; Dept of Respiratory Medicine Ehime, , Japan, 791-0280
    • NHO Kyushu Cancer Center Fukuoka, , Japan, 811-1395
    • Hyogo Cancer Center, Dept of Respiratory Medicine Hyogo, , Japan, 673-8558
    • National Cancer Center Hospital; Dept of Respiratory Medicine Kashiwa-shi, , Japan, 277-8577
    • Miyagi Cancer Center; Respiratory Medicine Miyagi, , Japan, 981-1293
    • Niigata Cancer Center Hospital; Internal Medicine Niigata, , Japan, 951-8566
    • OSAKA CITY GENERAL HOSPITAL;Medical Oncology Osaka, , Japan, 534-0021
    • Kindai University Hospital; Medical Oncology Osaka, , Japan, 589-8511
    • Shizuoka Cancer Center; Respiratory Internal Medicine Shizuoka, , Japan, 411-8777
  • Korea, Republic of,
    • Chungbuk National University Hospital Cheongju-si, , Korea, Republic of, 28644
    • Samsung Medical Center Seoul, , Korea, Republic of, (0)6351
    • Seoul National University Hospital Seoul, , Korea, Republic of, 03080
    • Severance Hospital, Yonsei University Health System Seoul, , Korea, Republic of, 03722
    • Asan Medical Center. Seoul, , Korea, Republic of, 138-736
  • Netherlands,
    • NKI The Netherlands Cancer Institute Amsterdam, , Netherlands, 1066 CX
    • Leids Universitair Medisch Centrum Leiden, , Netherlands, 2333 ZA
  • Poland,
    • Uniwersyteckie Centrum Kliniczne; Klinika Onkologii i Radioterapii Gdansk, , Poland, 80-214
    • Centrum Onkologii-Instytut im.M.Sklodowskiej Curie; Dept of Nuclear Med. and Endocrine Oncology Gliwice, , Poland, 44-101
    • Mazowieckie Centrum Leczenia Chorob Pluc i Gruzlicy; Dept of Pulmonology & subdiv. of oncology Otwock, , Poland, 05-400
    • Szpital Kliniczny Przemienienia Panskiego Uni. Medycznego im. Karola Marcinkowskiego; Chemotherapy Poznan, , Poland, 60-569
    • Centrum Onkologii Instytut im. M. Sklodowskiej-Curie, Klinika Nowotworow Ukladu Chlonnego Warszawa, , Poland, 02-781
  • Singapore,
    • National University Hospital; Haematology/Oncology Singapore, , Singapore, 119074
    • National Cancer Centre Singapore, , Singapore, 169610
  • Spain, Madrid
    • Centro Nacional de Investigaciones Oncológicas(CNIO); Gastrointestinal Cancer Clinical Research Unit Fuenlabrada, Madrid, Spain, 28942
  • Spain,
    • Hospital Universitari Vall dHebron; Oncology Barcelona, , Spain, 08035
    • Hospital Universitario de La Princesa; Servicio de Oncologia Madrid, , Spain, 28006
    • Hospital Universitario Ramon y Cajal; Servicio de Farmacia Madrid, , Spain, 28034
    • Hospital Universitario Clínico San Carlos; Servicio de Oncologia Madrid, , Spain, 28040
    • Hospital Universitario 12 de Octubre; Servicio de Oncologia Madrid, , Spain, 28041
    • Hospital Universitario La Paz; Servicio de Oncologia Madrid, , Spain, 28046
    • START Madrid. Centro Integral Oncologico Clara Campal; Unidad de Fase I-Oncologica Madrid, , Spain, 28050
    • Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia Malaga, , Spain, 29010
    • Hospital Universitario Virgen del Rocio; Servicio de Oncologia Sevilla, , Spain, 41013
  • Taiwan,
    • Changhua Christian Hospital Chang Hua, , Taiwan, 500
    • Taichung Veterans General Hospital Taichung, , Taiwan, 407
    • National Cheng Kung University Hospital Tainan, , Taiwan, 70457
    • Taipei Veterans General Hospital Taipei City, , Taiwan, 11217
    • National Taiwan University Hospital Taipei, , Taiwan, 10002
  • United Kingdom,
    • Cambridge University Hospitals NHS Foundation Trust - Addenbrookes Hospital Cambridge, , United Kingdom, CB2 0QQ
    • Sarah Cannon Research Institute London, , United Kingdom, W1G 6AD
    • Christie Hospital Nhs Trust; Medical Oncology Manchester, , United Kingdom, M2O 4BX

Sponsors and Collaborators

Hoffmann-La Roche

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT02568267
Other Study ID Numbers: 2015-003385-84
Study First Received:
Last Updated:
Health Authority:

Keywords provided by Hoffmann-La Roche:

Entrectinib

RXDX-101

TrkA

TrkB

TrkC

NTRK1

NTRK2

NTRK3

ROS1

ALK

Trk Fusions

NTRK Gene Rearrangements

ROS1 Fusions

ROS1 Gene Rearrangements

ALK Fusions

ALK Gene Rearrangements

Basket study

Non-small cell lung cancer

Colorectal cancer

Salivary gland cancers

Primary brain tumors

Melanoma

Sarcomas

Papillary thyroid cancer

Renal cell cancer

Pancreatic cancer

Breast cancer

Cholangiocarcinoma

Head & Neck cancers

Ovarian cancer

Neuroendocrine tumors

Anaplastic Large Cell Lymphoma

Additional relevant MeSH terms:

Neoplasms

Carcinoma, Non-Small-Cell Lung

Colorectal Neoplasms

Melanoma

Pancreatic Neoplasms

Sarcoma

Ovarian Neoplasms

Brain Neoplasms

Thyroid Neoplasms

Neuroendocrine Tumors

Cholangiocarcinoma

Salivary Gland Neoplasms

Head and Neck Neoplasms

Thyroid Cancer, Papillary

Lymphoma, Large-Cell, Anaplastic

Entrectinib

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on January 20, 2021