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A Phase I/IIa Open-Label, Dose Escalation and Cohort Expansion Trial of Oral TSR-011 in Patients With Advanced Solid Tumors and Lymphomas

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02048488
Recruitment Status : Completed
First Posted : January 29, 2014
Last Update Posted : March 26, 2019
Information provided by (Responsible Party):
Tesaro, Inc.

Brief Summary:

TSR-011 is a potent small molecule inhibitor of tyrosine kinases involved in cancer, including:

  1. Anaplastic lymphoma kinase (ALK)
  2. The tropomyosin-related kinases TRKA, TRKB, and TRKC

This is a sequential, open-label, non-randomized study with dose escalation in Phase 1, followed by expansion at a recommended phase 2 dose.

Condition or disease Intervention/treatment Phase
Solid Tumors Lymphomas Drug: TSR-011 Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 72 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/IIa Open-Label, Dose Escalation and Cohort Expansion Trial of Oral TSR-011 in Patients With Advanced Solid Tumors and Lymphomas
Study Start Date : October 2012
Actual Primary Completion Date : September 2016
Actual Study Completion Date : June 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: Experimental Drug TSR-011
Experimental Drug TSR-011
Drug: TSR-011
Number of cycles until progression or unacceptable toxicity develops.
Other Names:
  • ALK inhibitor, ALKi
  • TRK inhibitor

Primary Outcome Measures :
  1. Incidence of Adverse Events (AEs) [ Time Frame: Approximately 2 years ]

Secondary Outcome Measures :
  1. Area Under the Concentration-Time Curve (AUC) [ Time Frame: Day 1: 0-24 hrs after first dose; pre-dose on days 8 & 15; day 29: 0-24 hours ]
  2. Maximum Tolerated Dose (MTD) [ Time Frame: 28 days after first dose ]
    Phase 1, during the dose-escalation phase

  3. Response Rate (RR) [ Time Frame: approximately 2 years ]
    Phase 2

  4. Dose limiting toxicity (DLT) [ Time Frame: 28 days after first dose ]
    Phase 1, during the dose escalation phase

  5. Progression Free Survival (PFS) [ Time Frame: approximately 2 years ]
    Phase 2

  6. Recommended Phase 2 Dose (RP2D) [ Time Frame: approximately 2 years ]
    Phase 1

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

Inclusion Criteria:

  • To be considered eligible to participate in this study, all of the following requirements must be met:

    1. Patients in Phase 1 must have metastatic or locally advanced solid tumors who have failed to respond to standard therapy
    2. All patients must have confirmation of either ALK positive or TRK positive status.
    3. Patients in Phase 1 will not be required to have measurable disease. All patients in Phase 2a will be required to have measurable disease by RECIST.
    4. All patients enrolled in this study must have tumor tissue available.
    5. Patient (male or female) must be ≥ 18 years of age (except where age of majority is 16 years in a particular country, such as the United Kingdom).
    6. Patient must have performance status ≤2 on the ECOG Performance Scale.
    7. Patient must have an estimated life expectancy of at least 3 months.
    8. Patients must have adequate organ function.
    9. For patients previously treated with myelosuppressive therapy, at least 3 weeks must have elapsed and toxicity must have recovered to grade 1 or baseline. Non-myelosuppressive therapy patients must have recovered from all treatment-related toxicities. Fourteen days must have elapsed since palliative radiation for bone metastasis.
    10. Female patients of childbearing potential must have a negative serum pregnancy test and use adequate birth control for the duration of study participation and for 3 months after the last dose of study drug.
    11. The patient or his or her legal representative must be able to read, understand, and provide signed informed consent.
    12. Patient is able to understand the study procedures and agrees to participate in the study by giving written informed consent.

Exclusion Criteria:

  • Patients will not be deemed eligible for entry into this study if any of the following criteria are met:

    1. Patient has leukemia.
    2. Patient is a pregnant or lactating female.
    3. Patient has uncontrolled congestive heart failure, angina, or has had a myocardial infarction in the preceding 3 months.
    4. Ongoing cardiac dysrhythmias of NCI CTCAE Grade ≥2, atrial fibrillation of any grade, or QTc interval >450 msec.
    5. Patients with risk factors for Torsade de point and patients receiving concomitant medication with QT-prolonging medicines.
    6. Patient has an uncontrolled concurrent medical condition or disease.
    7. Patient has undergone bone marrow or stem cell transplantation in the past 6 months.
    8. Patient has a known hypersensitivity to the components of TSR-011 or the excipients.
    9. Patient has active or uncontrolled infection.
    10. Patient has a known psychiatric or substance abuse disorder.
    11. Patient has active second primary malignancy.
    12. Patient is observed to have a clinically active central nervous system (CNS) metastases or carcinomatous meningitis.
    13. Patient has any other severe concurrent disease which, in the judgment of the Investigator, would preclude study participation.
    14. Patient is known to be HIV positive or who has an AIDS-related illness.
    15. Patient has a known history of or active (treated or not) Hepatitis B or C.
    16. Patient has presence of ascites causing significant symptoms.
    17. A patient must stop taking any prescription, over-the-counter, or herbal remedy known to be an inhibitor or inducer of CYP3A4/5.

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 identifier (NCT number): NCT02048488

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United States, Arizona
Goodyear, Arizona, United States
Scottsdale, Arizona, United States
United States, California
Los Angeles, California, United States
United States, Tennessee
Nashville, Tennessee, United States
United States, Virginia
Norfolk, Virginia, United States
United States, Washington
Spokane, Washington, United States
Warsaw, Mazowieckie, Poland
Gdansk, Pomorskie, Poland
Olsztyn, Warminsko-Mazurskie, Poland
Poznan, Wielkopolskie, Poland
Madrid, Spain
Santiago de Compostela, Spain
Tainan City, Taiwan
Taipei, Taiwan
United Kingdom
London, United Kingdom
Sponsors and Collaborators
Tesaro, Inc.
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Study Director: Dmitri Bobilev, MD Tesaro, Inc.
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Tesaro, Inc. Identifier: NCT02048488    
Other Study ID Numbers: PR-20-5006-C
First Posted: January 29, 2014    Key Record Dates
Last Update Posted: March 26, 2019
Last Verified: March 2016
Keywords provided by Tesaro, Inc.:
non small cell lung cancer
Anaplastic lymphoma kinase
ALK tyrosine kinase receptor
ALK inhibitor
TRK inhibitor
tropomyosin receptor kinase
advanced malignancy
Additional relevant MeSH terms:
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Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action