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

NCT01449370 | Completed Phase 1 Results

• 1 other identifier: INK1117-001
• Study Type: interventional
• Target: 125
• Locations: 3 countries
• Sites: 5

Brief 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 TAK-117 when administered orally in subjects with advanced solid malignancies.

Conditions

Metastatic Solid Tumors

Keywords

INK1117; PIK3CA; KINASE; TUMOR; CANCER; Locally advanced or metastatic solid tumors; not eligible for standard of care therapy

Outcome Measures

Primary Outcomes (6)

• Maximum Tolerated Dose (MTD) of TAK-117

  MTD is highest dose level of TAK-117 at which no more than 1 out of 6 participants had a dose limiting toxicity (DLT) during first cycle. DLT was any 1 of following events occurring within first 21 days of Cycle 1 of TAK-117 administration, Grade 2: fasting hyperglycemia for \>14 days. Grade 3: nausea and/or vomiting/diarrhea for \>7 days; rash for \>7 days; thrombocytopenia with bleeding; fasting hyperglycemia for \>24 hours(hr). Grade \>=3:nonhematologic toxicity considered clinically significant by investigator. Grade 4:neutropenia (absolute neutrophil count \<=0.5\*10\^9per liter\[/L\]) for \>7 days in absence of growth factor support; neutropenia of any duration accompanied with fever \>=38.5 degree Celsius and/or systemic infection. Grade \>=4:hematologic toxicity. Inability to administer at least 75% of planned doses of TAK-117 within Cycle 1 due to its related toxicity;Any clinically significant occurrence that investigators and sponsor agreed would place participants at undue safety risk.

  Baseline up to Cycle 1 Day 21

• Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1

  Baseline up to Cycle 27 Day 45

• Number of Participants With Highest Level of TEAEs Severity

  Severity of AEs was evaluated based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0 as follow: Grade 1 (mild); Grade 2 (moderate); Grade 3 (severe); Grade 4 (life-threatening); Grade 5 (fatal).

  Baseline up to Cycle 27 Day 45

• Number of Participants With Clinically Meaningful Changes in Laboratory Values

  Baseline up to Cycle 27 Day 45

• Number of Participants With Clinically Meaningful Changes in Vital Signs

  Baseline up to Cycle 27 day 45

• Number of Participants With Clinically Meaningful Changes in Electrocardiogram (ECG)

  Baseline up to Cycle 27 Day 45

Secondary Outcomes (11)

• Overall Response Rate (ORR)

  Cycle 1 Day 8 up to Cycle 27 Day 1 or disease progression or death

• Duration of Objective Response

  Cycle 1 Day 8 up to Cycle 27 Day 1 or disease progression or death

• Clinical Benefit Rate (CBR)

  Cycle 1 Day 8 up to Cycle 27 Day 1 or disease progression or death

• Cmax: Maximum Observed Plasma Concentration for TAK-117

  Process A: Cycle 1 Day 1 pre-dose and at multiple timepoints (up to 24 hrs) post-dose; Process B: Cycle 1 Day 1 pre-dose and at multiple timepoints (up to 48 hrs) post-dose

• Ctrough: Observed Concentration at the End of Dosing Interval for TAK-117

  Process A: Cycle 1 Day 1 pre-dose and at multiple timepoints (up to 24 hrs) post-dose; Process B: Cycle 1 Day 1 pre-dose and at multiple timepoints (up to 48 hrs) post-dose

Study Arms (3)

Arm A

EXPERIMENTAL

TAK-117 administered once a day orally

Drug: TAK-117

Arm B

EXPERIMENTAL

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

Drug: TAK-117

Arm C

EXPERIMENTAL

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

Drug: TAK-117

Interventions

TAK-117 DRUG

oral administration of TAK-117, daily and intermittent schedules.

Arm A; Arm B; Arm C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Millennium Pharmaceuticals, Inc.: lead

Study Sites (5)

Unknown Facility

Boston, Massachusetts, United States

Location

Unknown Facility

Detroit, Michigan, United States

Location

Unknown Facility

Dallas, Texas, United States

Location

Unknown Facility

Barcelona, Spain

Location

Unknown Facility

Sutton, United Kingdom

Location

MeSH Terms

Conditions

Hereditary Sensory and Autonomic Neuropathies; Neoplasms

Interventions

serabelisib

Condition Hierarchy (Ancestors)

Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Monitor

  Millennium Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 11, 2011
• First Posted: October 10, 2011
• Study Start: October 1, 2011
• Primary Completion: July 1, 2015
• Study Completion: January 1, 2016
• Last Updated: March 9, 2017
• Results First Posted: March 9, 2017

Record last verified: 2017-01

Locations

ES (1); US (3); GB (1)