Dose Escalation Study of MLN1117 in Subjects With Advanced Cancer

Metastatic Solid Tumors Clinical Trial

Official title:

A Phase I, Dose Escalation Study of MLN1117 in Subjects With Advanced Solid Malignancies Followed by Expansion in Subjects With Measurable Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01449370
• Other study ID #: INK1117-001
• Status: Completed
• Phase: Phase 1
• First received: August 11, 2011
• Last updated: November 4, 2016
• Start date: October 2011
• Est. completion date: January 2016

Study information

• Verified date: November 2016
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationSpain: Ministry of HealthUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

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 MLN1117 when administered orally in subjects with advanced solid malignancies.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 124
• Est. completion date: January 2016
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 = 18 years, including males and females;

• 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 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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Metastatic Solid Tumors

Intervention

Drug:
• MLN1117
oral administration of MLN1117, daily and intermittent schedules.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Millennium Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose (MTD)		3 week cycle	Yes
Primary	Number of Adverse Events (AE)		From first dose of study drug through 30 days after last dose of study drug	Yes
Secondary	Plasma level of MLN1117	Pharmacokinetic profile	Days 1-21 of Cycles 1 & 2	No
Secondary	Biomarker levels	Pharmacodynamic profile in samplings of skin and/or tumor biopsies pre- and post-treatment.	Day 1 of Cycle 2 (Arms B & C only)	No
Secondary	Objective response rate	Complete response and partial response	Day 1 of Cycles 3 and beyond and at termination visit	No