MLN8237 in Adults With Nonhematological Malignancies, Followed by MLN8237 in Lung, Breast, Head and Neck or Gastroesophageal Malignancies

Non-Small Cell Lung Cancer Clinical Trial

Official title:

A Phase 1 Dose Escalation Study of MLN8237, an Aurora A Kinase Inhibitor, in Adult Patients With Nonhematological Malignancies, Followed by a Phase 2 of MLN8237 in Lung, Breast, Head and Neck, or Gastroesophageal Malignancies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01045421
• Other study ID #: C14007
• Secondary ID: 2008-006981-27
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: January 8, 2010
• Last updated: March 3, 2015
• Start date: February 2010
• Est. completion date: January 2014

Study information

• Verified date: March 2015
• Source: Millennium Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 273
• Est. completion date: January 2014
• Est. primary completion date: May 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 (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:

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

• 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

Study Design

Allocation: Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Drug:
• MLN8237
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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Millennium Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1: To assess the safety and tolerability of MLN8237, formulated as an enteric-coated tablet (ECT), on a 7-day dosing schedule for determining the recommended dose and schedule to be used in Phase 2		12 months	Yes
Primary	Phase 2: To estimate the antitumor activity of MLN8237 as measured by overall response rate		12 months	No
Secondary	Phase 1: To characterize the pharmacokinetics of MLN8237, formulated as ECT, administered on a 7-day dosing schedule and to describe any antitumor activity that may be observed with treatment in patients with advanced nonhematological malignancies		12 months	No
Secondary	Phase 2: To assess the relationship between clinical response and molecular markers of response		12 months	No
Secondary	Phase 2: To assess additional measures of antitumor activity, including time to progression, progression-free survival and duration of response		12 months	No
Secondary	Phase 2: To characterize the safety profile associated with MLN8237		12 months	Yes