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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) (STARTRK-2)

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ClinicalTrials.gov Identifier: NCT02568267
Recruitment Status : Active, not recruiting
First Posted : October 5, 2015
Last Update Posted : March 28, 2024
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Description
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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

Expanded Access : An investigational treatment associated with this study is no longer available outside the clinical trial.   More info ...

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 534 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 : November 19, 2015
Estimated Primary Completion Date : December 31, 2024
Estimated Study Completion Date : April 1, 2025

Resource links provided by the National Library of Medicine

Drug Information available for: Entrectinib

Arms and Interventions
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Arm Intervention/treatment
Experimental: NTRK1/2/3-rearranged NSCLC
Oral entrectinib (RXDX-101)
 Drug: Entrectinib
TrkA/B/C, ROS1, and ALK inhibitor
Other Name: RXDX-101
Experimental: ROS1-rearranged NSCLC
Oral entrectinib (RXDX-101)
 Drug: Entrectinib
TrkA/B/C, ROS1, and ALK inhibitor
Other Name: 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 Name: RXDX-101
Experimental: NTRK/1/2/3-rearranged mCRC
Oral entrectinib (RXDX-101)
 Drug: Entrectinib
TrkA/B/C, ROS1, and ALK inhibitor
Other Name: RXDX-101
Experimental: ROS1-rearranged mCRC
Oral entrectinib (RXDX-101)
 Drug: Entrectinib
TrkA/B/C, ROS1, and ALK inhibitor
Other Name: RXDX-101
Experimental: ALK-rearranged mCRC
Oral entrectinib (RXDX-101)
 Drug: Entrectinib
TrkA/B/C, ROS1, and ALK inhibitor
Other Name: RXDX-101
Experimental: NTRK1/2/3-rearranged other solid tumor
Oral entrectinib (RXDX-101)
 Drug: Entrectinib
TrkA/B/C, ROS1, and ALK inhibitor
Other Name: RXDX-101
Experimental: ROS1-rearranged other solid tumor
Oral entrectinib (RXDX-101)
 Drug: Entrectinib
TrkA/B/C, ROS1, and ALK inhibitor
Other Name: RXDX-101
Experimental: ALK-rearranged other solid tumor
Oral entrectinib (RXDX-101)
 Drug: Entrectinib
TrkA/B/C, ROS1, and ALK inhibitor
Other Name: RXDX-101


Outcome Measures
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Primary Outcome Measures :
  1. Objective Response Rate [ Time Frame: Approximately 24 months ]
    Assessed by blinded independent central review (BICR) using RECIST v1.1


Secondary Outcome Measures :
  1. Duration of Response [ Time Frame: Approximately 24 months ]
    Assessed by blinded independent central review (BICR) using RECIST v1.1

  2. Time to Response [ Time Frame: Approximately 24 months ]
    Assessed by blinded independent central review (BICR) using RECIST v1.1

  3. Clinical Benefit Rate [ Time Frame: Approximately 24 months ]
    Assessed by blinded independent central review (BICR) using RECIST v1.1

  4. Intracranial Tumor Response [ Time Frame: Approximately 24 months ]
    Assessed by blinded independent central review (BICR) using RANO or RANO-BM, as applicable

  5. CNS Progression-free Survival [ Time Frame: Approximately 24 months ]
    Assessed by blinded independent central review (BICR) using RANO or RANO-BM, as applicable

  6. Progression-free Survival [ Time Frame: Approximately 30 months ]
    Assessed by Kaplan-Meier method

  7. Overall Survival [ Time Frame: Approximately 36 months ]
    Assessed by Kaplan-Meier method

  8. Population PK [ Time Frame: Approximately 24 months ]
    Assessed by Kaplan-Meier method

  9. Adverse Events [ Time Frame: Approximately 36 months ]
    Type, incidence, severity, timing, seriousness, and relatedness of adverse events and laboratory abnormalities, graded by the NCI CTCAE

  10. Quality of Life [ Time Frame: 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

  11. Bone Growth and Bone Mineral Density [ Time Frame: Approximately 30 months ]
    Assessed with DHA scans

  12. Bone Biomarkers [ Time Frame: Approximately 30 months ]
    Measured by blood


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02568267


Locations
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Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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. Lancet Oncol. 2020 Jul;21(7):e341. Lancet Oncol. 2020 Aug;21(8):e372. Lancet Oncol. 2021 Oct;22(10):e428.

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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02568267    
Other Study ID Numbers: RXDX-101-02
2015-003385-84 ( EudraCT Number )
GO40782 ( Other Identifier: Hoffman-La Roche )
First Posted: October 5, 2015    Key Record Dates
Last Update Posted: March 28, 2024
Last Verified: March 2024

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
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
Additional relevant MeSH terms:
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Neoplasms
Carcinoma, Non-Small-Cell Lung
Colorectal Neoplasms
Melanoma
Pancreatic Neoplasms
Ovarian Neoplasms
Sarcoma
Brain Neoplasms
Thyroid Neoplasms
Cholangiocarcinoma
Neuroendocrine Tumors
Salivary Gland Neoplasms
Head and Neck Neoplasms
Thyroid Cancer, Papillary
Lymphoma, Large-Cell, Anaplastic
 Neoplasms by Site
Skin Diseases
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases