STARTRK-2: 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)

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Recruiting

CT.gov ID

NCT02568267

Collaborator

(none)

700

Enrollment

147

Locations

Arms

112.4

Anticipated Duration (Months)

4.8

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	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	Drug: Entrectinib	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

700 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Nov 19, 2015

Anticipated Primary Completion Date :

Dec 31, 2024

Anticipated Study Completion Date :

Apr 1, 2025

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

Objective Response Rate [Approximately 24 months]
Assessed by blinded independent central review (BICR) using RECIST v1.1

Secondary Outcome Measures

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
Clinical Benefit Rate [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
CNS Progression-free Survival [Approximately 24 months]
Assessed by blinded independent central review (BICR) using RANO or RANO-BM, as applicable
Progression-free Survival [Approximately 30 months]
Assessed by Kaplan-Meier method
Overall Survival [Approximately 36 months]
Assessed by Kaplan-Meier method
Population PK [Approximately 24 months]
Assessed by Kaplan-Meier method
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
Bone Growth and Bone Mineral Density [Approximately 30 months]
Assessed with DHA scans
Bone Biomarkers [Approximately 30 months]
Measured by blood

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Western Regional Medical Center at Cancer Treatment Centers of America	Goodyear	Arizona	United States	85338
2	Dignity Health St Joseph's Hospital and Medical Center	Phoenix	Arizona	United States	85013
3	Mayo Clinic	Scottsdale	Arizona	United States	85259
4	City of Hope Cancer Center; Division of Medical Oncology & Experimental Therapeutics	Duarte	California	United States	91010
5	Scripps Clinic	La Jolla	California	United States	92037
6	University of California San Diego Moores Cancer Center; Dept of Lung Cancer	La Jolla	California	United States	92093
7	University of Southern California Medical Center	Los Angeles	California	United States	90033
8	Univ Of California Irvine College Of Medicine; 300194620	Orange	California	United States	92868
9	Southern California Kaiser Permanente	San Diego	California	United States	92108
10	UCSF Mount Zion Medical Ctr	San Francisco	California	United States	94115
11	Sarcoma Oncology Center	Santa Monica	California	United States	90403
12	University of Colorado Cancer Center	Aurora	Colorado	United States	80045
13	Yale University	New Haven	Connecticut	United States	06510
14	Georgetown University Medical Center Lombardi Cancer Center	Washington	District of Columbia	United States	20007
15	Florida Cancer Specialists - Sarasota	Sarasota	Florida	United States	34232
16	H. Lee Moffitt Cancer Center and Research Inst.	Tampa	Florida	United States	33612
17	Cleveland Clinic Florida	Weston	Florida	United States	33331
18	University Cancer & Blood Center, LLC; Research	Athens	Georgia	United States	30607
19	Winship Cancer Institute	Atlanta	Georgia	United States	30322
20	Southeastern Regional Medical Center, Inc.	Newnan	Georgia	United States	30265
21	University of Hawaii Cancer Center	Honolulu	Hawaii	United States	96813
22	Northwestern University	Chicago	Illinois	United States	60611
23	Advocate Medical Group - Park Ridge, Luther Lane - Oncology	Park Ridge	Illinois	United States	60068
24	Midwestern Regional Medical Center	Zion	Illinois	United States	60099
25	Weinberg Cancer Institution at Franklin Square	Baltimore	Maryland	United States	21237
26	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
27	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
28	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
29	University of Michigan Comprehensive Cancer Center; Clinical Trials Office	Ann Arbor	Michigan	United States	48109
30	Karmanos Cancer Center	Detroit	Michigan	United States	48201
31	Henry Ford Hospital	Detroit	Michigan	United States	48202
32	Regents of the University of Minnesota	Minneapolis	Minnesota	United States	55455
33	Washington University	Saint Louis	Missouri	United States	63128
34	Comprehensive Cancer Centers of Nevada (CCCN) - Central Valley	Las Vegas	Nevada	United States	89169
35	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
36	North Shore Hem Onc Associates	East Setauket	New York	United States	11733
37	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
38	Levine Cancer Institute	Charlotte	North Carolina	United States	28204
39	Duke Cancer Institute	Durham	North Carolina	United States	27710
40	Cleveland Clinic	Cleveland	Ohio	United States	44195
41	OSU, James Cancer Hospital	Columbus	Ohio	United States	43210
42	Cancer Treatment Centers of America; Tulsa	Tulsa	Oklahoma	United States	74133
43	Providence Portland Medical Center	Portland	Oregon	United States	97213
44	Oregon Health & Science Univ	Portland	Oregon	United States	97239
45	Cancer Treatment Centers of America - Eastern Regional Medical Center	Philadelphia	Pennsylvania	United States	19124
46	Mary Crowley Medical Research Center	Dallas	Texas	United States	75230
47	University Hospital Medical Oncology Clinic; Harold C. Simmons Comprehensive Cancer Center	Dallas	Texas	United States	75390
48	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
49	Baylor Scott & White Health	Temple	Texas	United States	76502
50	University of Utah Hospitals & Clinics	Salt Lake City	Utah	United States	84132
51	Virginia Cancer Specialists, PC	Fairfax	Virginia	United States	22031
52	Virginia Oncology Associates - Hampton	Hampton	Virginia	United States	23666
53	University of Washington Seattle Cancer Care Alliance	Seattle	Washington	United States	98195
54	Wheaton Franciscan Cancer Care-All Saints	Franklin	Wisconsin	United States	53132
55	Border Medical Oncology Research Unit	Albury	New South Wales	Australia	2640
56	Liverpool Hospital	Liverpool	New South Wales	Australia	2170
57	Newcastle Private Hospital	New Lambton Heights	New South Wales	Australia	2305
58	Flinders Medical Centre	Bedford Park	South Australia	Australia	5042
59	Austin Health	Heidelberg	Victoria	Australia	3084
60	Antwerp University Hospital	Edegem		Belgium	2650
61	Beijing Cancer Hospital	Beijing		China	100142
62	Sichuan Provincial Cancer Hospital	Chengdu		China	610041
63	Cancer Center of Guangzhou Medical University	Guangzhou		China	510000
64	Harbin Medical University Cancer Hospital	Harbin		China	150081
65	Fudan University Shanghai Cancer Center	Shanghai City		China	200120
66	Shanghai chest hospital	Shanghai		China	200030
67	Shenzhen People's Hospital	Shenzhen		China	510852
68	Tianjin Cancer Hospital	Tianjin		China	300060
69	Union Hospital Tongji Medical College Huazhong University of Science and Technology	Wuhan City		China	430023
70	Zhejiang Cancer Hospital	Zhejiang		China	310022
71	Institut de Cancerologie de l Ouest	Angers		France	49055
72	Institut Bergonie; Oncologie	Bordeaux		France	33076
73	Centre Oscar Lambret; Chir Cancerologie General	Lille		France	59000
74	Centre Leon Berard; Departement Oncologie Medicale	Lyon		France	69373
75	Hôpital de la Timone; Oncologie Médicale Hématologie & Soins Palliatifs	Marseille cedex 5		France	13385
76	Hôpital Nord - AP-HM Marseille#; Service d'Oncologie Multidisciplinaire	Marseille		France	13015
77	Institut de Recherche en Cancérologie de Montpellier	Montpellier cedex 5		France	34298
78	Hôpital Européen Georges Pompidou; Hématologie Oncologie	Paris cedex 15		France	75908
79	Institut Curie; Oncologie Medicale	Paris		France	75231
80	Institut De Cancerologie De L'ouest - Rene Gauducheau - Biology	Saint Herblain		France	44805
81	Institut Claudius Regaud; Departement Oncologie Medicale	Toulouse		France	31059
82	Institut Gustave Roussy; Pathologie Thoracique	Villejuif cedex		France	94805
83	Charite Universitaetsmedizin Berlin - Campus Charite Mitte ; Charite Comprehensive Cancer Center	Berlin		Germany	10117
84	Evang. Lungenklinik Berlin Klinik für Pneumologie	Berlin		Germany	13125
85	Universitaetsklinikum Carl Gustav Carus TU Dresden	Dresden		Germany	01307
86	Asklepios-Fachkliniken Muenchen-Gauting; Onkologie	Gauting		Germany	82131
87	Universitaetsmedizin Goettingen; Abteilung Haematologie und Onkologie	Göttingen		Germany	37075
88	NCT Uniklinikum Heidelberg; Medizinische Onkologie	Heidelberg		Germany	69120
89	Universitaetsklinikum Koeln; Innere Medizin I, Haematologie	Köln		Germany	50937
90	Hong Kong Integrated Oncology Centre	Hong Kong		Hong Kong
91	Princess Margaret Hospital	Hong Kong		Hong Kong
92	The University of Hong Kong	Hong Kong		Hong Kong
93	Queen Elizabeth Hospital	Kowloon		Hong Kong
94	The Chinese University of Hong Kong	Shatin		Hong Kong	123456
95	Seconda Università degli Studi di Napoli; Servizio Epato-Gastroenterologia	Napoli	Campania	Italy	80131
96	Università Campus Bio-Medico di Roma; Oncologia Medica	Roma	Lazio	Italy	128
97	Azienda Ospedaliero Universitaria San Martino; Lung Cancer Unit	Genova	Liguria	Italy	16132
98	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano	Lombardia	Italy	20133
99	Azienda Socio Sanitaria Territoriale Niguarda (Ospedale Niguarda Ca' Granda); Oncologico -Onc.Falck	Milano	Lombardia	Italy	20162
100	Fondazione del Piemonte per l'Oncologia - IRCCS;Ematologia	Candiolo	Piemonte	Italy	10060
101	Azienda Ospedaliero-Universitaria S.Luigi Gonzaga; SSD Oncologia Polmonare	Orbassano	Piemonte	Italy	10043
102	A.O Città della Salute e della Scienza di Torino; Colorectal Cancer Unit (CRCU) - SSCVD	Torino	Piemonte	Italy	10126
103	Azienda Ospedaliero Universitaria Pisana; Uff. Sperim. Clin. U.O. Farmaceutica	Pisa	Toscana	Italy	56126
104	Azienda Ospedaliera di Perugia Ospedale S. Maria della Misericordia ; S.C. Oncologia Medica	Perugia	Umbria	Italy	6132
105	IOV - Istituto Oncologico Veneto - IRCCS; Oncologia Medica II	Padova	Veneto	Italy	35128
106	Aichi Cancer Center Hospital; Respiratory Medicine	Aichi		Japan	464-8681
107	NHO Shikoku Cancer Center; Dept of Respiratory Medicine	Ehime		Japan	791-0280
108	NHO Kyushu Cancer Center	Fukuoka		Japan	811-1395
109	Hyogo Cancer Center, Dept of Respiratory Medicine	Hyogo		Japan	673-8558
110	National Cancer Center Hospital; Dept of Respiratory Medicine	Kashiwa-shi		Japan	277-8577
111	Miyagi Cancer Center; Respiratory Medicine	Miyagi		Japan	981-1293
112	Niigata Cancer Center Hospital; Internal Medicine	Niigata		Japan	951-8566
113	OSAKA CITY GENERAL HOSPITAL;Medical Oncology	Osaka		Japan	534-0021
114	Kindai University Hospital; Medical Oncology	Osaka		Japan	589-8511
115	Shizuoka Cancer Center; Respiratory Internal Medicine	Shizuoka		Japan	411-8777
116	Chungbuk National University Hospital	Cheongju-si		Korea, Republic of	28644
117	Seoul National University Hospital	Seoul		Korea, Republic of	03080
118	Severance Hospital, Yonsei University Health System	Seoul		Korea, Republic of	03722
119	Samsung Medical Center	Seoul		Korea, Republic of	06351
120	Asan Medical Center.	Seoul		Korea, Republic of	138-736
121	NKI The Netherlands Cancer Institute	Amsterdam		Netherlands	1066 CX
122	Leids Universitair Medisch Centrum	Leiden		Netherlands	2333 ZA
123	Uniwersyteckie Centrum Kliniczne; Klinika Onkologii i Radioterapii	Gdańsk		Poland	80-214
124	Centrum Onkologii-Instytut im.M.Sklodowskiej Curie; Dept of Nuclear Med. and Endocrine Oncology	Gliwice		Poland	44-101
125	Mazowieckie Centrum Leczenia Chorob Pluc i Gruzlicy; Dept of Pulmonology & subdiv. of oncology	Otwock		Poland	05-400
126	Szpital Kliniczny Przemienienia Panskiego Uni. Medycznego im. Karola Marcinkowskiego; Chemotherapy	Poznań		Poland	60-569
127	Centrum Onkologii Instytut im. M. Sklodowskiej-Curie, Klinika Nowotworow Ukladu Chlonnego	Warszawa		Poland	02-781
128	National University Hospital; Haematology/Oncology	Singapore		Singapore	119074
129	National Cancer Centre	Singapore		Singapore	169610
130	Centro Nacional de Investigaciones Oncológicas(CNIO); Gastrointestinal Cancer Clinical Research Unit	Fuenlabrada	Madrid	Spain	28942
131	Vall d´Hebron Institute of Oncology (VHIO), Barcelona	Barcelona		Spain	08035
132	Hospital Universitario de La Princesa; Servicio de Oncologia	Madrid		Spain	28006
133	Hospital Universitario Ramon y Cajal; Servicio de Farmacia	Madrid		Spain	28034
134	Hospital Universitario Clínico San Carlos; Servicio de Oncologia	Madrid		Spain	28040
135	Hospital Universitario 12 de Octubre; Servicio de Oncologia	Madrid		Spain	28041
136	Hospital Universitario La Paz; Servicio de Oncologia	Madrid		Spain	28046
137	Centro Integral Oncologico Clara Campal; Servicio de Oncología	Madrid		Spain	28050
138	Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia	Malaga		Spain	29010
139	Hospital Universitario Virgen del Rocio; Servicio de Oncologia	Sevilla		Spain	41013
140	Changhua Christian Hospital	Chang Hua		Taiwan	500
141	National Cheng Kung University Hospital	Tainan		Taiwan	70457
142	Taipei Veterans General Hospital	Taipei City		Taiwan	11217
143	National Taiwan University Hospital	Taipei		Taiwan	10002
144	Taichung Veterans General Hospital	Xitun Dist.		Taiwan	40705
145	Addenbrookes Hospital	Cambridge		United Kingdom	CB2 0QQ
146	Sarah Cannon Research Institute	London		United Kingdom	W1G 6AD
147	Christie Hospital Nhs Trust; Medical Oncology	Manchester		United Kingdom	M2O 4BX