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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02568267




Registration number
NCT02568267
Ethics application status
Date submitted
2/10/2015
Date registered
5/10/2015
Date last updated
21/06/2024

Titles & IDs
Public title
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)
Scientific 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
Secondary ID [1] 0 0
2015-003385-84
Secondary ID [2] 0 0
RXDX-101-02
Universal Trial Number (UTN)
Trial acronym
STARTRK-2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 0 0
Cholangiocarcinoma 0 0
Colorectal Cancer 0 0
Head and Neck Neoplasms 0 0
Lymphoma, Large-Cell, Anaplastic 0 0
Melanoma 0 0
Neuroendocrine Tumors 0 0
Non-Small Cell Lung Cancer 0 0
Ovarian Cancer 0 0
Pancreatic Cancer 0 0
Papillary Thyroid Cancer 0 0
Primary Brain Tumors 0 0
Renal Cell Carcinoma 0 0
Sarcomas 0 0
Salivary Gland Cancers 0 0
Adult Solid Tumor 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)
Cancer 0 0 0 0
Malignant melanoma
Cancer 0 0 0 0
Pancreatic
Cancer 0 0 0 0
Ovarian and primary peritoneal
Cancer 0 0 0 0
Sarcoma (also see 'Bone') - soft tissue
Cancer 0 0 0 0
Bone
Cancer 0 0 0 0
Brain
Cancer 0 0 0 0
Thyroid
Cancer 0 0 0 0
Biliary tree (gall bladder and bile duct)
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Cancer 0 0 0 0
Neuroendocrine tumour (NET)
Cancer 0 0 0 0
Head and neck
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - Entrectinib

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)

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)


Treatment: Drugs: Entrectinib
TrkA/B/C, ROS1, and ALK inhibitor
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Objective Response Rate
Timepoint [1] 0 0
Approximately 24 months
Secondary outcome [1] 0 0
Duration of Response
Timepoint [1] 0 0
Approximately 24 months
Secondary outcome [2] 0 0
Time to Response
Timepoint [2] 0 0
Approximately 24 months
Secondary outcome [3] 0 0
Clinical Benefit Rate
Timepoint [3] 0 0
Approximately 24 months
Secondary outcome [4] 0 0
Intracranial Tumor Response
Timepoint [4] 0 0
Approximately 24 months
Secondary outcome [5] 0 0
CNS Progression-free Survival
Timepoint [5] 0 0
Approximately 24 months
Secondary outcome [6] 0 0
Progression-free Survival
Timepoint [6] 0 0
Approximately 30 months
Secondary outcome [7] 0 0
Overall Survival
Timepoint [7] 0 0
Approximately 36 months
Secondary outcome [8] 0 0
Population PK
Timepoint [8] 0 0
Approximately 24 months
Secondary outcome [9] 0 0
Adverse Events
Timepoint [9] 0 0
Approximately 36 months
Secondary outcome [10] 0 0
Quality of Life
Timepoint [10] 0 0
Approximately 24 months
Secondary outcome [11] 0 0
Bone Growth and Bone Mineral Density
Timepoint [11] 0 0
Approximately 30 months
Secondary outcome [12] 0 0
Bone Biomarkers
Timepoint [12] 0 0
Approximately 30 months

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
19/11/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/04/2025
Actual
Sample size
Target
Accrual to date
Final
534
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [2] 0 0
Newcastle Private Hospital - New Lambton Heights
Recruitment hospital [3] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [4] 0 0
Austin Health - Heidelberg
Recruitment postcode(s) [1] 0 0
2170 - Liverpool
Recruitment postcode(s) [2] 0 0
2305 - New Lambton Heights
Recruitment postcode(s) [3] 0 0
5042 - Bedford Park
Recruitment postcode(s) [4] 0 0
3084 - Heidelberg
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
District of Columbia
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Georgia
Country [8] 0 0
United States of America
State/province [8] 0 0
Illinois
Country [9] 0 0
United States of America
State/province [9] 0 0
Maryland
Country [10] 0 0
United States of America
State/province [10] 0 0
Massachusetts
Country [11] 0 0
United States of America
State/province [11] 0 0
Michigan
Country [12] 0 0
United States of America
State/province [12] 0 0
Minnesota
Country [13] 0 0
United States of America
State/province [13] 0 0
Missouri
Country [14] 0 0
United States of America
State/province [14] 0 0
Nevada
Country [15] 0 0
United States of America
State/province [15] 0 0
New York
Country [16] 0 0
United States of America
State/province [16] 0 0
North Carolina
Country [17] 0 0
United States of America
State/province [17] 0 0
Ohio
Country [18] 0 0
United States of America
State/province [18] 0 0
Oklahoma
Country [19] 0 0
United States of America
State/province [19] 0 0
Oregon
Country [20] 0 0
United States of America
State/province [20] 0 0
Pennsylvania
Country [21] 0 0
United States of America
State/province [21] 0 0
Texas
Country [22] 0 0
United States of America
State/province [22] 0 0
Utah
Country [23] 0 0
United States of America
State/province [23] 0 0
Virginia
Country [24] 0 0
United States of America
State/province [24] 0 0
Washington
Country [25] 0 0
Belgium
State/province [25] 0 0
Edegem
Country [26] 0 0
China
State/province [26] 0 0
Beijing
Country [27] 0 0
China
State/province [27] 0 0
Chengdu
Country [28] 0 0
China
State/province [28] 0 0
Guangzhou
Country [29] 0 0
China
State/province [29] 0 0
Harbin
Country [30] 0 0
China
State/province [30] 0 0
Shanghai City
Country [31] 0 0
China
State/province [31] 0 0
Shanghai
Country [32] 0 0
China
State/province [32] 0 0
Shenzhen
Country [33] 0 0
China
State/province [33] 0 0
Tianjin
Country [34] 0 0
China
State/province [34] 0 0
Wuhan City
Country [35] 0 0
China
State/province [35] 0 0
Zhejiang
Country [36] 0 0
France
State/province [36] 0 0
Angers
Country [37] 0 0
France
State/province [37] 0 0
Bordeaux
Country [38] 0 0
France
State/province [38] 0 0
Lyon
Country [39] 0 0
France
State/province [39] 0 0
Marseille cedex 5
Country [40] 0 0
France
State/province [40] 0 0
Marseille
Country [41] 0 0
France
State/province [41] 0 0
Montpellier cedex 5
Country [42] 0 0
France
State/province [42] 0 0
Paris
Country [43] 0 0
France
State/province [43] 0 0
Saint Herblain
Country [44] 0 0
France
State/province [44] 0 0
Toulouse
Country [45] 0 0
France
State/province [45] 0 0
Villejuif cedex
Country [46] 0 0
Germany
State/province [46] 0 0
Berlin
Country [47] 0 0
Germany
State/province [47] 0 0
Dresden
Country [48] 0 0
Germany
State/province [48] 0 0
Göttingen
Country [49] 0 0
Germany
State/province [49] 0 0
Heidelberg
Country [50] 0 0
Germany
State/province [50] 0 0
Köln
Country [51] 0 0
Hong Kong
State/province [51] 0 0
Hong Kong
Country [52] 0 0
Hong Kong
State/province [52] 0 0
Kowloon
Country [53] 0 0
Hong Kong
State/province [53] 0 0
Shatin
Country [54] 0 0
Italy
State/province [54] 0 0
Campania
Country [55] 0 0
Italy
State/province [55] 0 0
Lazio
Country [56] 0 0
Italy
State/province [56] 0 0
Lombardia
Country [57] 0 0
Italy
State/province [57] 0 0
Toscana
Country [58] 0 0
Italy
State/province [58] 0 0
Umbria
Country [59] 0 0
Italy
State/province [59] 0 0
Veneto
Country [60] 0 0
Japan
State/province [60] 0 0
Aichi
Country [61] 0 0
Japan
State/province [61] 0 0
Ehime
Country [62] 0 0
Japan
State/province [62] 0 0
Fukuoka
Country [63] 0 0
Japan
State/province [63] 0 0
Hyogo
Country [64] 0 0
Japan
State/province [64] 0 0
Kashiwa-shi
Country [65] 0 0
Japan
State/province [65] 0 0
Miyagi
Country [66] 0 0
Japan
State/province [66] 0 0
Niigata
Country [67] 0 0
Japan
State/province [67] 0 0
Osaka
Country [68] 0 0
Japan
State/province [68] 0 0
Shizuoka
Country [69] 0 0
Korea, Republic of
State/province [69] 0 0
Seoul
Country [70] 0 0
Netherlands
State/province [70] 0 0
Amsterdam
Country [71] 0 0
Netherlands
State/province [71] 0 0
Leiden
Country [72] 0 0
Poland
State/province [72] 0 0
Gdansk
Country [73] 0 0
Poland
State/province [73] 0 0
Gliwice
Country [74] 0 0
Poland
State/province [74] 0 0
Pozna?
Country [75] 0 0
Poland
State/province [75] 0 0
Warszawa
Country [76] 0 0
Singapore
State/province [76] 0 0
Singapore
Country [77] 0 0
Spain
State/province [77] 0 0
Madrid
Country [78] 0 0
Spain
State/province [78] 0 0
Barcelona
Country [79] 0 0
Spain
State/province [79] 0 0
Malaga
Country [80] 0 0
Spain
State/province [80] 0 0
Sevilla
Country [81] 0 0
Taiwan
State/province [81] 0 0
Tainan
Country [82] 0 0
Taiwan
State/province [82] 0 0
Taipei City
Country [83] 0 0
Taiwan
State/province [83] 0 0
Taipei
Country [84] 0 0
United Kingdom
State/province [84] 0 0
Cambridge
Country [85] 0 0
United Kingdom
State/province [85] 0 0
London
Country [86] 0 0
United Kingdom
State/province [86] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT02568267
Trial related presentations / publications
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.
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. Erratum In: J Comp Eff Res. 2022 May;11(7):545-548. doi: 10.2217/cer-2021-0131c1.
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.
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. Erratum In: Lancet Oncol. 2020 Feb;21(2):e70. doi: 10.1016/S1470-2045(20)30007-3. Lancet Oncol. 2020 Jul;21(7):e341. doi: 10.1016/S1470-2045(20)30346-6.
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. Erratum In: Lancet Oncol. 2020 Feb;21(2):e70. doi: 10.1016/S1470-2045(20)30029-2. Lancet Oncol. 2020 Jul;21(7):e341. doi: 10.1016/S1470-2045(20)30345-4. Lancet Oncol. 2020 Aug;21(8):e372. doi: 10.1016/S1470-2045(20)30382-X. Lancet Oncol. 2021 Oct;22(10):e428. doi: 10.1016/S1470-2045(21)00538-6.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02568267