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

NCT ID: NCT02048488

Last Updated: 2019-03-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-31
• Study Completion Date: 2018-06-30

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.

Conditions

Solid Tumors; Lymphomas

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Experimental Drug TSR-011

Experimental Drug TSR-011

Group Type: EXPERIMENTAL

TSR-011

Intervention Type: DRUG

Number of cycles until progression or unacceptable toxicity develops.

Interventions

TSR-011

Number of cycles until progression or unacceptable toxicity develops.

Intervention Type: DRUG

Other Intervention Names

ALK inhibitor, ALKi; TRK inhibitor

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tesaro, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dmitri Bobilev, MD

Role: STUDY_DIRECTOR

Tesaro, Inc.

Locations

Goodyear, Arizona, United States

Scottsdale, Arizona, United States

Los Angeles, California, United States

Nashville, Tennessee, United States

Norfolk, Virginia, United States

Spokane, Washington, United States

Poznan, Greater Poland Voivodeship, Poland

Warsaw, Masovian Voivodeship, Poland

Gdansk, Pomeranian Voivodeship, Poland

Olsztyn, Warmian-Masurian Voivodeship, Poland

Madrid, , Spain

Santiago de Compostela, , Spain

Tainan City, , Taiwan

Taipei, , Taiwan

London, , United Kingdom

Countries

United States; Poland; Spain; Taiwan; United Kingdom

References

Lin CC, Arkenau HT, Lu S, Sachdev J, de Castro Carpeno 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.

Reference Type: DERIVED

PMID: 31217479 (View on PubMed)

Other Identifiers

PR-20-5006-C

Identifier Type: -

Identifier Source: org_study_id