Study of MLN8237 in Patients With Advanced Solid Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT00962091
First received: August 18, 2009
Last updated: July 1, 2013
Last verified: July 2013
  Purpose

This is an open-label, multicenter, phase 1 study to evaluate the safety and pharmacokinetic properties of an oral solution and enteric-coated tablet (ECT) formulations of MLN8237 in patients with advanced solid tumors. This study will be conducted in 3 parts, A, B, and C.


Condition Intervention Phase
Advanced Solid Tumors
Drug: MLN8237
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label, Phase 1 Study of the Relative Bioavailability, Food Effect, Safety and Tolerability of MLN8237 in Patients With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by Millennium Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Ratio of geometric mean dose-normalized Cmax and dose-normalized AUC0-tlast of oral solution vs powder in capsule formulations with 90% confidence intervals (CI) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    To estimate the relative bioavailability of an oral solution of MLN8237 in reference to a powder in capsule (PIC) formulation.

  • Ratio of geometric mean Cmax and AUC0-tlast of MLN8237 administered as an oral solution with food vs without food and 90% CI [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    To characterize the effect of food on the pharmacokinetics (PK) of MLN8237 administered as an oral solution formulation

  • Cmax, Tmax, AUC over the dosing interval of the oral solution following multiple-dose administration [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    To characterize the multiple dose steady-state PK of the oral solution formulation of MLN8237

  • Ratio of geometric mean Cmax and AUC0-tlast and AUCinf of MLN8237 administered as an enteric-coated capsule (ECT) with food vs without food and 90% CI [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    To characterize the effect of food on the single-dose PK of MLN8237 administered as an ECT formulation

  • Number of adverse events and serious adverse events [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    To characterize the multiple dose safety and tolerability of MLN8237


Secondary Outcome Measures:
  • Response, according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    To describe any antitumor activity that may be observed with MLN8237 treatment


Enrollment: 53
Study Start Date: September 2009
Study Completion Date: April 2012
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MLN8237- Part A
Oral solution vs Powder in Capsule (PIC)
Drug: MLN8237

Prior to initiation of Part A, an accelerated dose escalation cohort will be evaluated. The first cohort will be administered a single 15-mg dose of the oral solution administered on Day 1 of Cycle 1. Once the safety and tolerability of study drug is established in this cohort, Part A will commence as described below.

Part A: patients will receive either a single 25 mg dose of MLN8237 (oral solution) or a 50 mg powder in capsule (PIC) dose of MLN8237 on Day 1 of Cycle 1, followed by administration of a single dose of the respective alternate formulation on Day 1 of Cycle 2. Dosing at 50 mg twice a day of the PIC formulation for 7 days (Days 3-9) will then be resumed after the single-dose administration of the oral solution or PIC for both Cycle 1 and Cycle 2 followed by a 14 day rest period. Beginning with Cycle 3, MLN8237 will be administered at 50 mg PIC twice a day for 7 days followed by a 14 day rest period in 21-day cycles.

Experimental: MLN8237- Part B
Oral Solution MLN8237 Fed, Oral Solution MLN8237 Fasted
Drug: MLN8237
Patients will receive a single dose of MLN8237 (oral solution) with or without a standard high fat breakfast on Day 1 of Cycle 1, followed by administration under the respective alternate food intake condition (fasted to fed, or fed to fasted; N = 7 per sequence) on Day 1 in Cycle 2. The dose of MLN8237 (oral solution) to be administered in this food effect assessment will be determined from the relative bioavailability estimate in Part A. Dosing at X mg twice/day MLN8237 (oral solution) for 7 days will be resumed after the single dose administration of the oral solution for both Cycle 1 and Cycle 2 followed by a 14-day rest period. Beginning with Cycle 3, MLN8237 will be administered at the 50 mg twice/day PIC formulation with 7 days of dosing followed by a 14 day rest period in 21-day cycles.
Experimental: MLN8237- Part C
Enteric Coated Tablet (ECT) MLN8237 Fed, ECT MLN8237 Fasted
Drug: MLN8237

Patients will receive a single 50-mg dose of MLN8237 enteric-coated tablet (ECT) with or without a standard high fat breakfast on Day 1 of Cycle 1, followed by administration under the respective alternate food intake condition (fasted to fed, or fed to fasted; N = 7 per sequence) on Day 1 in Cycle 2.

Dosing at 40 mg twice/day MLN8237 ECT for 7 days will be resumed after the single dose administration of ECT for Cycle 1, followed by a 14-day rest period. In Cycle 2, MLN8237 ECT will be administered as a single dose of 50 mg on Day 1, followed by either 40 or 50 mg twice/day for Day 3 through the morning dose of Day 9 and followed by a 14-day rest period. Beginning with Cycle 3, MLN8237 ECT will be administered twice a day for 7 days followed by a 14 day rest period in 21-day cycles.


  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

  • 18 years or older
  • Histologically or cytologically confirmed metastatic and/or advanced solid tumor
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Female patients who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or abstain from heterosexual
  • Male patients who agree to practice effective barrier contraception or agree to abstain from heterosexual intercourse
  • Voluntary written consent
  • Suitable venous access for study-required blood sampling
  • Measurable disease
  • Recovered from effects of prior antineoplastic therapy

Exclusion Criteria:

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

  • Female patients who are pregnant or lactating
  • Serious medical or psychiatric illness that could interfere with protocol completion
  • Major surgery within 14 days of first dose of MLN8237
  • Antineoplastic therapy, radiation therapy or any experimental therapy 21 days prior to first dose of MLN8237
  • Nitrosoureas or mitomycin-C within 6 weeks before the first dose of MLN8237.
  • Autologous stem cell transplant within 3 months before the first dose of MLN8237, or prior allogeneic stem cell transplant at any time.
  • Active infection requiring systemic therapy, or other serious infection
  • Inability to swallow oral medication
  • Gastrointestinal (GI) disease or GI procedure that could interfere with oral absorption or tolerance of MLN8237
  • Symptomatic brain metastasis
  • Uncontrolled cardiovascular condition
  • Diagnosis or treatment of another malignancy within 2 years preceding first dose of study drug except nonmelanoma skin cancer or in situ malignancy completely resected
  • Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C
  • Lactose-intolerant (Parts A and B only)
  • Prior history of metabolic acidosis (Parts A and B only)
  • Use of enzyme-inducing antiepileptic drugs such as phenytoin, carbamazepine or phenobarbital, or rifampin, rifabutin, rifapentine or St. John's wort within 14 days prior to the first dose of MLN8237
  • A medical condition requiring use of pancreatic enzymes; or daily, chronic , or regular use of proton pump inhibitors (PPI); or histamine (H2) receptor antagonists. Patients who intermittently use these medications must meet the following:

    • No use of PPI within 7 days of first dose of MLN8237
    • No use of H2 antagonist or pancreatic enzymes within 24 hours of first dose of MLN8237
  • Patients requiring full systemic anticoagulation
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00962091

Locations
United States, California
Premiere Oncology, A Medical Corporation
Santa Monica, California, United States, 90404
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Investigators
Study Director: Medical Monitor Millennium Pharmaceuticals, Inc.
  More Information

No publications provided

Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT00962091     History of Changes
Other Study ID Numbers: C14010
Study First Received: August 18, 2009
Last Updated: July 1, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Millennium Pharmaceuticals, Inc.:
Area under the plasma concentration versus time curve (AUC)
Maximum plasma concentration (Cmax)
Area under the plasma concentration versus time curve zero to the time of the last quantifiable concentration (AUC0-tlast)
Confidence intervals (CI)
Time of first observed maximum plasma concentration (Tmax)

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on August 20, 2014