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)
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: 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
Keywords: 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
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2015-10-05
Enrollment: 534
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Objective Response Rate
timeFrame: Approximately 24 months
Secondary outcomes:
measure: Duration of Response
timeFrame: Approximately 24 months
measure: Time to Response
timeFrame: Approximately 24 months
measure: Clinical Benefit Rate
timeFrame: Approximately 24 months
measure: Intracranial Tumor Response
timeFrame: Approximately 24 months
measure: CNS Progression-free Survival
timeFrame: Approximately 24 months
measure: Progression-free Survival
timeFrame: Approximately 30 months
measure: Overall Survival
timeFrame: Approximately 36 months
measure: Population PK
timeFrame: Approximately 24 months
measure: Adverse Events
timeFrame: Approximately 36 months
measure: Quality of Life
timeFrame: Approximately 24 months
measure: Bone Growth and Bone Mineral Density
timeFrame: Approximately 30 months
measure: Bone Biomarkers
timeFrame: Approximately 30 months
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Dignity Health St Joseph's Hospital and Medical Center
state: Arizona
city: Phoenix
country: United States
facility: Mayo Clinic
state: Arizona
city: Duarte
country: United States
facility: City of Hope Cancer Center
state: California
city: Duarte
country: United States
facility: City of Hope Duarte - Comprehensive Cancer Center, Investigational Drug Services
state: California
city: La Jolla
country: United States
facility: Scripps Clinic
state: California
city: La Jolla
country: United States
facility: University of California San Diego Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: Southern California Kaiser Permanente
state: California
city: Los Angeles
country: United States
facility: University of Southern California Medical Center
state: California
city: Orange
country: United States
facility: Univ Of California Irvine College Of Medicine
state: California
city: San Francisco
country: United States
facility: UCSF Mount Zion Medical Ctr
state: California
city: San Francisco
country: United States
facility: UCSF Mission Bay
state: California
city: Santa Monica
country: United States
facility: Sarcoma Oncology Center
state: California
city: Santa Monica
country: United States
facility: Sarcoma Oncology Research Center LLC
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Washington
country: United States
facility: Georgetown University Medical Center Lombardi Cancer Center
state: District of Columbia
city: Sarasota
country: United States
facility: Florida Cancer Specialists - Sarasota
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Inst.
state: Florida
city: Athens
country: United States
facility: University Cancer & Blood Center, LLC
state: Georgia
city: Atlanta
country: United States
facility: Winship Cancer Institute
state: Georgia
city: Newnan
country: United States
facility: Southeastern Regional Medical Center, Inc.
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Park Ridge
country: United States
facility: Advocate Medical Group - Park Ridge, Luther Lane - Oncology
state: Illinois
city: Zion
country: United States
facility: Midwestern Regional Medical Center
state: Illinois
city: Baltimore
country: United States
facility: Weinberg Cancer Institution at Franklin Square
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hosp CAR
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Detroit
country: United States
facility: Karmanos Cancer Center
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Minneapolis
country: United States
facility: Regents of the University of Minnesota
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada (CCCN) - Central Valley
state: Nevada
city: East Setauket
country: United States
facility: North Shore Hem Onc Associates
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Durham
country: United States
facility: Duke Cancer Institute
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Columbus
country: United States
facility: OSU, James Cancer Hospital
state: Ohio
city: Tulsa
country: United States
facility: Cancer Treatment Centers of America
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Portland
country: United States
facility: Oregon Health & Science Univ
state: Oregon
city: Dallas
country: United States
facility: Mary Crowley Medical Research Center
state: Texas
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Temple
country: United States
facility: Baylor Scott & White Health
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Hospitals & Clinics
state: Utah
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates - Hampton
state: Virginia
city: Seattle
country: United States
facility: University of Washington Seattle Cancer Care Alliance
state: Washington
city: Liverpool
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: Newcastle
country: Australia
facility: Newcastle Private Hospital
state: New South Wales
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Edegem
country: Belgium
facility: Antwerp University Hospital
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Chengdu
country: China
facility: Sichuan Provincial Cancer Hospital
city: Guangzhou
country: China
facility: Cancer Center of Guangzhou Medical University
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
city: Shanghai
country: China
facility: Shanghai chest hospital
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
city: Shenzhen
country: China
facility: Shenzhen People's Hospital
city: Wuhan City
country: China
facility: Union Hospital Tongji Medical College Huazhong University of Science and Technology
city: Angers
country: France
facility: Institut de Cancerologie de l Ouest
city: Bordeaux
country: France
facility: Institut Bergonie
city: Lyon
country: France
facility: Centre Leon Berard
city: Marseille cedex 20
country: France
facility: Hôpital Nord - AP-HM Marseille#
city: Marseille cedex 5
country: France
facility: Hôpital de la Timone
city: Montpellier
country: France
facility: Institut de Recherche en Cancérologie de Montpellier
city: Paris
country: France
facility: Institut Curie
city: Saint Herblain
country: France
facility: Institut De Cancerologie De L'ouest - Rene Gauducheau - Biology
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Villejuif cedex
country: France
facility: Institut Gustave Roussy
city: Berlin
country: Germany
facility: Evang. Lungenklinik Berlin Klinik für Pneumologie
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus TU Dresden
city: Göttingen
country: Germany
facility: Universitaetsmedizin Goettingen
city: Heidelberg
country: Germany
facility: NCT Uniklinikum Heidelberg
city: Köln
country: Germany
facility: Universitaetsklinikum Koeln
city: Hong Kong
country: Hong Kong
facility: Princess Margaret Hospital
city: Hong Kong
country: Hong Kong
facility: The University of Hong Kong
city: Kowloon
country: Hong Kong
facility: Queen Elizabeth Hospital
city: Shatin
country: Hong Kong
facility: The Chinese University of Hong Kong
city: Napoli
country: Italy
facility: Seconda Università degli Studi di Napoli
state: Campania
city: Roma
country: Italy
facility: Università Campus Bio-Medico di Roma
state: Lazio
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
state: Lombardia
city: Milano
country: Italy
facility: Azienda Socio Sanitaria Territoriale Niguarda (Ospedale Niguarda Ca' Granda)
state: Lombardia
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
state: Toscana
city: Perugia
country: Italy
facility: Azienda Ospedaliera di Perugia Ospedale S. Maria della Misericordia
state: Umbria
city: Padova
country: Italy
facility: IOV - Istituto Oncologico Veneto - IRCCS
state: Veneto
city: Aichi
country: Japan
facility: Aichi Cancer Center Hospital
city: Chuo
country: Japan
facility: National Cancer Center Hospital
city: Fukuoka
country: Japan
facility: NHO Kyushu Cancer Center
city: Hyogo
country: Japan
facility: Hyogo Cancer Center, Dept of Respiratory Medicine
city: Kashiwa-shi
country: Japan
facility: National Cancer Center Hospital
city: Matsuyama-shi
country: Japan
facility: NHO Shikoku Cancer Center
city: Miyagi
country: Japan
facility: Miyagi Cancer Center
city: Niigata
country: Japan
facility: Niigata Cancer Center Hospital
city: Osaka
country: Japan
facility: Osaka City General Hospital
city: Osaka
country: Japan
facility: Kindai University Hospital
city: Shizuoka
country: Japan
facility: Shizuoka Cancer Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center.
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Amsterdam
country: Netherlands
facility: NKI The Netherlands Cancer Institute
city: Leiden
country: Netherlands
facility: Leids Universitair Medisch Centrum
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Gliwice
country: Poland
facility: Centrum Onkologii-Instytut im.M.Sklodowskiej Curie
city: Pozna?
country: Poland
facility: Szpital Kliniczny Przemienienia Panskiego Uni. Medycznego im. Karola Marcinkowskiego
city: Warszawa
country: Poland
facility: Centrum Onkologii Instytut im. M. Sklodowskiej-Curie, Klinika Nowotworow Ukladu Chlonnego
city: Singapore
country: Singapore
facility: National University Hospital
city: Singapore
country: Singapore
facility: National Cancer Centre
city: Fuenlabrada
country: Spain
facility: Centro Nacional de Investigaciones Oncológicas(CNIO)
state: Madrid
city: Barcelona
country: Spain
facility: Vall d?Hebron Institute of Oncology (VHIO), Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Malaga
country: Spain
facility: Hospital Clinico Universitario Virgen de la Victoria
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Cambridge
country: United Kingdom
facility: Addenbrookes Hospital
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute
city: Manchester
country: United Kingdom
facility: The Christie
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Sullivan WG, Hatswell AJ. Letter re: 'Intrapatient comparisons of efficacy in a single-arm trial of entrectinib in tumour-agnostic indications'. ESMO Open. 2021 Dec;6(6):100282. doi: 10.1016/j.esmoop.2021.100282. Epub 2021 Oct 28. No abstract available.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: Sigal D, Tartar M, Xavier M, Bao F, Foley P, Luo D, Christiansen J, Hornby Z, Maneval EC, Multani P. Activity of Entrectinib in a Patient With the First Reported NTRK Fusion in Neuroendocrine Cancer. J Natl Compr Canc Netw. 2017 Nov;15(11):1317-1322. doi: 10.6004/jnccn.2017.7029.