Dose Escalation Study of TAK-117 (MLN1117) in Subjects With Advanced Cancer

Millennium Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Metastatic Solid Tumors

Treatments: Drug: TAK-117

Study type: Interventional

Funder types: Industry

Identifiers

NCT01449370

INK1117-001

Details and patient eligibility

About

The purpose of this study is to determine the maximum tolerated dose (MTD) and/or optimal biologic dose(OBD), safety and tolerability, dose-limiting toxicity (DLT) of TAK-117 when administered orally in subjects with advanced solid malignancies.

Enrollment: 125 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Subjects have had their PIK3CA gene mutation status assessed prior to enrolling into the study
• Subjects must have documented disease progression prior to enrolling into the study
• locally advanced or metastatic solid tumors with the exception of primary brain tumor, and have failed or are not eligible for standard of care therapy.
• Age greater than or equal to (>=) 18 years, including males and females;
• Eastern cooperative oncology group (ECOG) performance status (PS) 0-1;
• Adequate organ function;
• Male subjects must be surgically sterile or must agree to use physician-approved contraception during the study and for 30 days following the last study drug administration;
• Ability to swallow oral medications;
• Ability to understand and willingness to sign informed consent prior to initiation of any study procedures;
• For women of child-bearing potential, negative serum pregnancy test within 14 days prior to the first study drug administration and use of physician-approved method of birth control from 30 days prior to the first study drug administration to 30 days following the last study drug administration

Exclusion criteria

• Diagnosis of primary brain tumor; untreated brain metastasis or history of leptomeningeal disease or spinal cord compression;
• Received prior cancer or other investigational therapy within 2 weeks prior to the first administration of study drug;
• Have received a systemic corticosteroid within one week prior to the first administration of study drug;
• Clinically significant cardiac disease;
• Myocardial infarction or unstable angina within 6 months prior to the first administration of study drug;
• Malabsorption ;
• Poorly controlled diabetes mellitus;
• Pregnancy (positive serum or urine pregnancy test) or breast feeding;
• Untreated brain metastasis or history of leptomeningeal disease or spinal cord compression;
• Failed to recover from the reversible effects of prior anticancer therapies;
• Have received a selective phosphoinositide-3-kinase alpha isoform (PI3K-alpha) inhibitor
• Other clinically significant co-morbidities, such as uncontrolled pulmonary disease, active central nervous system (CNS) disease, active infection, or any other condition that could compromise the subject's participation in the study
• Known human immunodeficiency virus (HIV) infection
• Have a secondary malignancy within the last 3 years prior to first dose of study drug, excluding treated non-melanoma skin cancer, carcinoma in situ, or locally-treated prostate cancer

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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125 participants in 3 patient groups

Arm A

Experimental group

Description:

TAK-117 administered once a day orally

Treatment:

Drug: TAK-117

Arm B

Experimental group

Description:

TAK-117 administered orally intermittently, once every other day (Monday, Wednesday, and Friday) each week

Treatment:

Drug: TAK-117

Arm C

Experimental group

Description:

TAK-117 administered orally intermittently, once a day for 3 consecutive days (Monday, Tuesday, and Wednesday) each week

Treatment:

Drug: TAK-117