Alisertib in Adults With Nonhematological Malignancies, Followed by Alisertib in Lung, Breast, Head and Neck or Gastroesophageal Malignancies

NCT ID: NCT01045421

Last Updated: 2016-08-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 273 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-02-28
• Study Completion Date: 2014-04-30

Brief Summary

This is an open-label, multicenter study with a phase 1 dose escalation portion and a 2-stage, phase 2 portion, investigating MLN8237 (alisertib) in patients with advanced nonhematological malignancies.

Detailed Description

Following the determination of the Recommended Phase 2 Dose (RP2D) and schedule (Phase 1), 20 response-evaluable patients in each of the 5 tumor indications will be enrolled (Phase 2-Stage 1). An interim analysis will determine which tumor indications will proceed to enroll an additional 25 patients (Phase 2-Stage 2) to further evaluate Overall Response Rate (ORR) and other secondary endpoints.

Conditions

Advanced Nonhematological Malignancies; Non-Small Cell Lung Cancer; Small Cell Lung Cancer; Metastatic Breast Cancer; Head and Neck Squamous Cell Carcinoma; Gastroesophageal Adenocarcinoma

Study Design

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

Study Groups

MLN8237 (Alisertib)

MLN8237 administered as an enteric-coated tablet (ECT)

Group Type: EXPERIMENTAL

MLN8237 (Alisertib)

Intervention Type: DRUG

Phase 1:

MLN8237 will be administered orally twice a day on a 7-day dosing schedule

Phase 2:

MLN8237 will be administered orally at the maximum tolerated dose determined in Phase 1 for 7-days followed by a minimum 14-day rest period.

Interventions

MLN8237 (Alisertib)

Phase 1:

MLN8237 will be administered orally twice a day on a 7-day dosing schedule

Phase 2:

MLN8237 will be administered orally at the maximum tolerated dose determined in Phase 1 for 7-days followed by a minimum 14-day rest period.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 18 years or older
• Histologically or cytologically confirmed metastatic and/or advanced solid tumor (Phase 1 only)
• Phase 2 requires Non-small cell lung cancer (NSCLC); Small-cell lung cancer; Breast adenocarcinoma (female patients only); Squamous cell cancer of the head and neck (HNSCC); or Gastroesophageal adenocarcinoma
• 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 intercourse
• Male patients who agree to practice effective barrier contraception or agree to abstain from heterosexual intercourse
• Voluntary written consent
• Wiling to comply with scheduled visits, treatment plan, laboratory tests and other trial procedures
• Measurable disease (Phase 2 only)

Exclusion Criteria

• Female patients who are pregnant or lactating
• Serious medical or psychiatric illness that could interfere with protocol completion
• Receipt of more than 2 previous cytotoxic chemotherapeutic regimens (4 previous regimens for breast cancer). There is no limit on the number of prior noncytotoxic therapies
• Prior treatment with Aurora A-targeted agents, including MLN8237
• Prior treatment with high-dose chemotherapy
• Prior allogeneic bone marrow or other organ transplant
• Antineoplastic therapy, radiation therapy or any experimental therapy 21 days prior to first dose of MLN8237
• Symptomatic brain metastasis
• Radiotherapy to greater than 25% of bone marrow
• 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
• Myocardial infarction within 6 months of enrollment
• Uncontrolled cardiovascular condition
• Major surgery within 14 days of first dose of MLN8237
• Active infection requiring systemic therapy, or other serious infection
• Inability to swallow oral medication
• Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C
• Patients requiring full systemic anticoagulation
• History of uncontrolled sleep apnea syndrome
• Treatment with clinically significant enzyme inducers within 14 days prior to the first dose of MLN8237 and during the study

• 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

Houston, Texas, United States

Salt Lake City, Utah, United States

Countries

United States

References

Melichar B, Adenis A, Lockhart AC, Bennouna J, Dees EC, Kayaleh O, Obermannova R, DeMichele A, Zatloukal P, Zhang B, Ullmann CD, Schusterbauer C. Safety and activity of alisertib, an investigational aurora kinase A inhibitor, in patients with breast cancer, small-cell lung cancer, non-small-cell lung cancer, head and neck squamous-cell carcinoma, and gastro-oesophageal adenocarcinoma: a five-arm phase 2 study. Lancet Oncol. 2015 Apr;16(4):395-405. doi: 10.1016/S1470-2045(15)70051-3. Epub 2015 Feb 27.

Reference Type: DERIVED

PMID: 25728526 (View on PubMed)

Falchook G, Kurzrock R, Gouw L, Hong D, McGregor KA, Zhou X, Shi H, Fingert H, Sharma S. Investigational Aurora A kinase inhibitor alisertib (MLN8237) as an enteric-coated tablet formulation in non-hematologic malignancies: phase 1 dose-escalation study. Invest New Drugs. 2014 Dec;32(6):1181-7. doi: 10.1007/s10637-014-0121-6. Epub 2014 Jun 1.

Reference Type: DERIVED

PMID: 24879333 (View on PubMed)

Other Identifiers

2008-006981-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1171-0859

Identifier Type: REGISTRY

Identifier Source: secondary_id

C14007

Identifier Type: -

Identifier Source: org_study_id