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

• ClinicalTrials.gov Identifier: NCT02048488
• Recruitment Status: Completed
• First Posted: January 29, 2014
• Last Update Posted: March 26, 2019
• Sponsor: Tesaro, Inc.
• Information provided by (Responsible Party): Tesaro, Inc.

Study Description

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

Study Design

• 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

Arms and Interventions

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

Outcome Measures

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

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

Poland

Warsaw, Mazowieckie, Poland

Gdansk, Pomorskie, Poland

Olsztyn, Warminsko-Mazurskie, Poland

Poznan, Wielkopolskie, Poland

Spain

Madrid, Spain

Santiago de Compostela, Spain

Taiwan

Tainan City, Taiwan

Taipei, Taiwan

United Kingdom

London, United Kingdom

Sponsors and Collaborators

Tesaro, Inc.

Investigators

• Study Director: Dmitri Bobilev, MD; Tesaro, Inc.

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Lin CC, Arkenau HT, Lu S, Sachdev J, de Castro Carpeño J, Mita M, Dziadziuszko R, Su WC, Bobilev D, Hughes L, Chan J, Zhang ZY, Weiss GJ. A phase 1, open-label, dose-escalation trial of oral TSR-011 in patients with advanced solid tumours and lymphomas. Br J Cancer. 2019 Jul;121(2):131-138. doi: 10.1038/s41416-019-0503-9. Epub 2019 Jun 20.

• Responsible Party: Tesaro, Inc.
• ClinicalTrials.gov Identifier: NCT02048488
• Other Study ID Numbers: PR-20-5006-C
• First Posted: January 29, 2014
• Last Update Posted: March 26, 2019
• Last Verified: March 2016

Keywords provided by Tesaro, Inc.:

non small cell lung cancer; NSCLC; Anaplastic lymphoma kinase; ALK tyrosine kinase receptor; ALK+; TRK+; ALK inhibitor; TRK inhibitor; tropomyosin receptor kinase; TRKA; TRKB; TRKC; advanced malignancy

Additional relevant MeSH terms:

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Belizatinib; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action