A Dose Escalation Study of MLN7243 (TAK-243) in Adult Participants With Advanced Solid Tumors

NCT ID: NCT02045095

Last Updated: 2019-03-14

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-01-31
• Study Completion Date: 2016-11-09

Brief Summary

The purpose of this study is to evaluate safety and tolerability (establish maximum tolerated dose [MTD], inform the recommended phase 2 dose [RP2D], and identify the dose-limiting toxicities [DLTs]) of MLN7243.

Detailed Description

This is a single arm Phase I study with multiple dosing cohorts as noted below:

• Schedule A: MLN7243 1 mg
• Schedule A: MLN7243 2 mg
• Schedule A: MLN7243 4 mg
• Schedule A: MLN7243 8 mg
• Schedule A: MLN7243 12 mg
• Schedule A: MLN7243 18 mg
• Schedule A: MLN7243 Homozygous Mutant 4 mg

Conditions

Advanced Malignant Solid Tumors

Study Design

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

Study Groups

Schedule A: MLN7243 1 mg

MLN7243 1 milligram (mg), infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or disease progression (PD) or discontinuation of study for another reason, or until study is stopped.

Group Type: EXPERIMENTAL

MLN7243

Intervention Type: DRUG

Dose escalation stage Schedule A: Intravenous infusion on Days 1, 4, 8, 11 for a 21-day treatment cycle.

Schedule B: Intravenous infusion on Days 1, 8, 15 for a 28-day treatment cycle.

Dose expansion stage: MLN7243 will be administered following schedule A (twice-weekly, 21-day dosing) and/or B (once-weekly, 28-day dosing).

Schedule A: MLN7243 2 mg

MLN7243 2 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD, or discontinuation of study for another reason, or until study is stopped.

Group Type: EXPERIMENTAL

MLN7243

Intervention Type: DRUG

Dose escalation stage Schedule A: Intravenous infusion on Days 1, 4, 8, 11 for a 21-day treatment cycle.

Schedule B: Intravenous infusion on Days 1, 8, 15 for a 28-day treatment cycle.

Dose expansion stage: MLN7243 will be administered following schedule A (twice-weekly, 21-day dosing) and/or B (once-weekly, 28-day dosing).

Schedule A: MLN7243 4 mg

MLN7243 4 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.

Group Type: EXPERIMENTAL

MLN7243

Intervention Type: DRUG

Dose escalation stage Schedule A: Intravenous infusion on Days 1, 4, 8, 11 for a 21-day treatment cycle.

Schedule B: Intravenous infusion on Days 1, 8, 15 for a 28-day treatment cycle.

Dose expansion stage: MLN7243 will be administered following schedule A (twice-weekly, 21-day dosing) and/or B (once-weekly, 28-day dosing).

Schedule A: MLN7243 8 mg

MLN7243 8 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.

Group Type: EXPERIMENTAL

MLN7243

Intervention Type: DRUG

Dose escalation stage Schedule A: Intravenous infusion on Days 1, 4, 8, 11 for a 21-day treatment cycle.

Schedule B: Intravenous infusion on Days 1, 8, 15 for a 28-day treatment cycle.

Dose expansion stage: MLN7243 will be administered following schedule A (twice-weekly, 21-day dosing) and/or B (once-weekly, 28-day dosing).

Schedule A: MLN7243 12 mg

MLN7243 12 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.

Group Type: EXPERIMENTAL

MLN7243

Intervention Type: DRUG

Dose escalation stage Schedule A: Intravenous infusion on Days 1, 4, 8, 11 for a 21-day treatment cycle.

Schedule B: Intravenous infusion on Days 1, 8, 15 for a 28-day treatment cycle.

Dose expansion stage: MLN7243 will be administered following schedule A (twice-weekly, 21-day dosing) and/or B (once-weekly, 28-day dosing).

Schedule A: MLN7243 18 mg

MLN7243 18 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.

Group Type: EXPERIMENTAL

MLN7243

Intervention Type: DRUG

Dose escalation stage Schedule A: Intravenous infusion on Days 1, 4, 8, 11 for a 21-day treatment cycle.

Schedule B: Intravenous infusion on Days 1, 8, 15 for a 28-day treatment cycle.

Dose expansion stage: MLN7243 will be administered following schedule A (twice-weekly, 21-day dosing) and/or B (once-weekly, 28-day dosing).

Schedule A: MLN7243 Homozygous Mutant 4 mg

MLN7243 homozygous mutant 4 mg, infusion, intravenously over 10-minutes, on Days 1, 4, 8, and 11 followed by 10 days of rest in a 21-day treatment cycle for a maximum of 12 months, or until symptomatic deterioration or PD or discontinuation of study for another reason, or until study is stopped.

Group Type: EXPERIMENTAL

MLN7243

Intervention Type: DRUG

Dose escalation stage Schedule A: Intravenous infusion on Days 1, 4, 8, 11 for a 21-day treatment cycle.

Schedule B: Intravenous infusion on Days 1, 8, 15 for a 28-day treatment cycle.

Dose expansion stage: MLN7243 will be administered following schedule A (twice-weekly, 21-day dosing) and/or B (once-weekly, 28-day dosing).

Interventions

MLN7243

Dose escalation stage Schedule A: Intravenous infusion on Days 1, 4, 8, 11 for a 21-day treatment cycle.

Schedule B: Intravenous infusion on Days 1, 8, 15 for a 28-day treatment cycle.

Dose expansion stage: MLN7243 will be administered following schedule A (twice-weekly, 21-day dosing) and/or B (once-weekly, 28-day dosing).

Intervention Type: DRUG

Other Intervention Names

TAK-243

Eligibility Criteria

Inclusion Criteria

1. Male or female participants 18 years or older.

2. Participants must have a histologically confirmed diagnosis of an advanced, metastatic malignant solid tumor and must have failed or exhausted standard therapies or for which no standard therapy is available.

3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

4. Participants with adequate hematologic and organ function.

5. All participants must have radiographically detectable tumors with measurable disease as defined by RECIST (version 1.1).

6. Participants undergoing a biopsy procedure must have accessible lesions which are safe to biopsy.

7. Recovered (that is, less than or equal to (<=) Grade 1 toxicity) from the reversible effects of prior antineoplastic therapy, except alopecia.

8. Female participants who are postmenopausal for at least 1 year before the screening visit, surgically sterile, or agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 4 months after the last dose of study drug, or agree to practice true abstinence.

Male participants who agree to practice effective barrier contraception during the entire study treatment period through 4 months after the last dose of study drug or agree to practice true abstinence.

9. Suitable venous access for the study-required blood sampling including PK sampling.

Exclusion Criteria

1. Participants with clinically significant pre-existing cardiac impairment.

2. Participants homozygous for the ABCG2 (BCRP) c.421C greater than (>) 1 A polymorphism will be excluded from the study until the safety of a minimum of the first 3 dose levels has been characterized and the sponsor confirms that such participants can be enrolled at doses that are at least 3-fold lower than the most recently determined safe and tolerable dose among at least 3 dose limiting toxicities (DLT)-evaluable non-homozygous participants.

3. Participants with known active central nervous system (CNS) lesions are excluded. Systemic antineoplastic therapy or investigational agents within 21 days before the first dose of study drug.

4. Radiotherapy within 14 days before the first dose of study drug is not allowed except for limited field radiotherapy for palliative bone pain.

5. For participants where tumor biopsies are required or requested:

• Any known coagulation abnormalities that would contraindicate the tumor biopsy procedure.
• Ongoing therapy with any anticoagulant or antiplatelet agents (example, aspirin, clopidogrel [Plavix®], heparin, or warfarin).

6. Major surgery within 28 days before the first dose of MLN7243.

7. Life-threatening illness unrelated to cancer.

8. Any evidence of active infection or antibiotic therapy within 14 days before the first dose of MLN7243.

9. Known human immunodeficiency virus (HIV) positivity or AIDS-related illness, hepatitis B virus, and hepatitis C virus.

10. Participants whose weight is less than (<) 40 kilogram (kg).

11. History of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease.

12. Female participants who are lactating and breastfeeding or have a positive serum pregnancy test during the Screening period or a positive urine pregnancy test on Day 1 before first dose of study drug.

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

Sponsors

Millennium Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor

Role: STUDY_DIRECTOR

Millennium Pharmaceuticals, Inc.

Locations

Boston, Massachusetts, United States

St Louis, Missouri, United States

Cleveland, Ohio, United States

Philadelphia, Pennsylvania, United States

Charleston, South Carolina, United States

Nashville, Tennessee, United States

San Antonio, Texas, United States

Countries

United States

Other Identifiers

U1111-1203-6359

Identifier Type: OTHER

Identifier Source: secondary_id

C33001

Identifier Type: -

Identifier Source: org_study_id