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

Millennium Pharmaceuticals

Status and phase: Terminated; Phase 1

Conditions: Advanced Malignant Solid Tumors

Treatments: Drug: MLN7243

Study type: Interventional

Funder types: Industry

Identifiers

NCT02045095

U1111-1203-6359 (Other Identifier)

C33001

Details and patient eligibility

About

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.

Full 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

Enrollment: 29 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

Each participant must meet all of the following inclusion criteria to be enrolled in the study:

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

Participants meeting any of the following exclusion criteria are not to be enrolled in the study:

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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29 participants in 7 patient groups

Schedule A: MLN7243 1 mg

Experimental group

Description:

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.

Treatment:

Drug: MLN7243

Schedule A: MLN7243 2 mg

Experimental group

Description:

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.

Treatment:

Drug: MLN7243

Schedule A: MLN7243 4 mg

Experimental group

Description:

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.

Treatment:

Drug: MLN7243

Schedule A: MLN7243 8 mg

Experimental group

Description:

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.

Treatment:

Drug: MLN7243

Schedule A: MLN7243 12 mg

Experimental group

Description:

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.

Treatment:

Drug: MLN7243

Schedule A: MLN7243 18 mg

Experimental group

Description:

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.

Treatment:

Drug: MLN7243

Schedule A: MLN7243 Homozygous Mutant 4 mg

Experimental group

Description:

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.

Treatment:

Drug: MLN7243