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

NCT02045095 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: C33001U1111-1203-6359
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 7

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.

Conditions

Advanced Malignant Solid Tumors

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (6)

• Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

  Baseline up to 30 days after last dose of study drug (Cycle 10 Day 41)

• Number of Participants With Laboratory Related TEAEs by System Organ Class (SOC)

  Baseline up to 30 days after last dose of study drug (Cycle 10 Day 41)

• Number of Participants With Vital Sign Related TEAEs by Preferred Term (PT)

  Baseline up to 30 days after last dose of study drug (Cycle 10 Day 41)

• Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities

  Cycle 1 Day 1 up to Cycle 1 Day 11

• Number of Participants With Clinically Significant Echocardiogram Abnormalities

  Cycle 1 Day 2 up to 30 days after last dose of study drug (Cycle 10 Day 41)

• Number of Participants With TEAEs Related to Tropinin I and T

  Baseline up to 30 days after last dose of study drug (Cycle 10 Day 41)

Secondary Outcomes (13)

• Ceoi: Plasma Concentration at the End of Infusion for TAK-243

  Cycle 1 Day 1 and 11: pre-infusion to end of infusion (up to 10 minutes)

• AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-243

  Cycle 1 Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose; Cycle 1 Day 11 pre-dose and at multiple time points (up to 72 hours) post-dose

• AUCτ: Area Under the Plasma Concentration-time Curve Over the Dosing Interval for TAK-243

  Cycle 1 Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose; Cycle 1 Day 11 pre-dose and at multiple time points (up to 72 hours) post-dose

• AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-243

  Cycle 1 Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose; Cycle 1 Day 11 pre-dose and at multiple time points (up to 72 hours) post-dose

• CL: Total Clearance After Intravenous Administration for TAK-243

  Cycle 1 Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose; Cycle 1 Day 11 pre-dose and at multiple time points (up to 72 hours) post-dose

Study Arms (7)

Schedule A: MLN7243 1 mg

EXPERIMENTAL

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.

Drug: MLN7243

Schedule A: MLN7243 2 mg

EXPERIMENTAL

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.

Drug: MLN7243

Schedule A: MLN7243 4 mg

EXPERIMENTAL

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.

Drug: MLN7243

Schedule A: MLN7243 8 mg

EXPERIMENTAL

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.

Drug: MLN7243

Schedule A: MLN7243 12 mg

EXPERIMENTAL

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.

Drug: MLN7243

Schedule A: MLN7243 18 mg

EXPERIMENTAL

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.

Drug: MLN7243

Schedule A: MLN7243 Homozygous Mutant 4 mg

EXPERIMENTAL

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.

Drug: MLN7243

Interventions

MLN7243 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).

Also known as: TAK-243

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female participants 18 years or older.
• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Participants with adequate hematologic and organ function.
• All participants must have radiographically detectable tumors with measurable disease as defined by RECIST (version 1.1).
• Participants undergoing a biopsy procedure must have accessible lesions which are safe to biopsy.
• Recovered (that is, less than or equal to (\<=) Grade 1 toxicity) from the reversible effects of prior antineoplastic therapy, except alopecia.
• 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.
• Suitable venous access for the study-required blood sampling including PK sampling.

You may not qualify if:

• Participants with clinically significant pre-existing cardiac impairment.
• 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.
• 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.
• Radiotherapy within 14 days before the first dose of study drug is not allowed except for limited field radiotherapy for palliative bone pain.
• 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).
• Major surgery within 28 days before the first dose of MLN7243.
• Life-threatening illness unrelated to cancer.
• Any evidence of active infection or antibiotic therapy within 14 days before the first dose of MLN7243.
• Known human immunodeficiency virus (HIV) positivity or AIDS-related illness, hepatitis B virus, and hepatitis C virus.
• Participants whose weight is less than (\<) 40 kilogram (kg).
• History of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease.
• 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.

Sponsors & Collaborators

• Millennium Pharmaceuticals, Inc.: lead

Study Sites (7)

Unknown Facility

Boston, Massachusetts, United States

Location

Unknown Facility

St Louis, Missouri, United States

Location

Unknown Facility

Cleveland, Ohio, United States

Location

Unknown Facility

Philadelphia, Pennsylvania, United States

Location

Unknown Facility

Charleston, South Carolina, United States

Location

Unknown Facility

Nashville, Tennessee, United States

Location

Unknown Facility

San Antonio, Texas, United States

Location

MeSH Terms

Interventions

TAK-243

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Monitor

  Millennium Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2013
• First Posted: January 24, 2014
• Study Start: January 31, 2014
• Primary Completion: November 9, 2016
• Study Completion: November 9, 2016
• Last Updated: March 14, 2019
• Results First Posted: March 14, 2019

Record last verified: 2018-11

Locations

US (7)