Clinical Study of Oral IGF-1R Inhibitor in Subjects With Advanced Refractory Solid Tumors

NCT ID: NCT01779336

Last Updated: 2014-09-29

Basic Information

• Recruitment Status: SUSPENDED
• Clinical Phase: PHASE1
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-12-31
• Study Completion Date: 2014-12-31

Brief Summary

Clinical study of oral IGF-1R inhibitor PL225B in subjects with advanced refractory solid tumors. The primary objective is to determine the maximum tolerated dose and dose limiting toxicity (ies) of oral IGF-1R inhibitor PL225B in subjects with advanced refractory solid tumors.

Detailed Description

An open label multicentre Phase 1 study of oral IGF-1R inhibitor PL225B in subjects with advanced refractory solid tumors. This is a dose-finding trial using the modified Accelerated Titration Design with 3 new subjects per cohort and 100% dose increments in the accelerated phase followed by standard phase with 40% dose increments.Subjects will receive study drug on a daily basis for twenty-one (21) days according to the dose and schedule specified for a particular cohort of therapy. Toxicity profile of the drug will be assessed during Cycle 1 of subject treatment in each cohort for determination of Maximum Tolerated Dose (MTD) according to the schedule given below.

Conditions

Advanced Refractory Solid Tumors

Study Design

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

Study Groups

PL225B

Patients will receive study drug on a daily basis until disease progression or unacceptable toxicity in sequential cohorts following accelerated titration design.

Group Type: EXPERIMENTAL

PL225B

Intervention Type: DRUG

• Patients will receive study drug on a daily basis for twenty-one (21) days according to the dose and schedule specified for a particular cohort of therapy.
• This 21 day administration will define a treatment cycle.
• Patients may receive consecutive treatment cycles until evidence of disease progression, intolerance of therapy, or withdrawal from the protocol as specified.

Interventions

PL225B

• Patients will receive study drug on a daily basis for twenty-one (21) days according to the dose and schedule specified for a particular cohort of therapy.
• This 21 day administration will define a treatment cycle.
• Patients may receive consecutive treatment cycles until evidence of disease progression, intolerance of therapy, or withdrawal from the protocol as specified.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Subjects having histologically and/or cytologically confirmed non-haematological malignancy that is metastatic or unresectable and for which standard curative or palliative treatment does not exist or is no longer effective
• Subjects should have measurable or evaluable disease
• Subjects of either sex, of all races and ethnic groups, and ≥18 years of age
• ECOG (Eastern Cooperative Oncology Group) performance status 0-1
• Subjects with life expectancy of at least 4 months
• Subjects with fasting plasma glucose ≤ 125 mg/dL and HbA1c < 6.5 % at screening Subjects with fasting plasma glucose ≤150 mg/dL and HbA1c ≤ 7.0 % at screening for the Diabetes Expansion Cohort.
• For the Diabetes Expansion Cohort - Subjects with known history of type 2 diabetes mellitus that are well-controlled on a stable dose of oral anti-diabetic agents such as metformin and/or sulfonylureas for 4 weeks prior to screening.
• Subjects must have normal organ and marrow function as defined below:

1. Absolute neutrophil count ≥ 1500/cmm

2. Platelets ≥ 100,000/cmm

3. Total bilirubinwithin normal limits of the institution

4. AST/ALT ≤ 2.5 X institutional upper limit of normal (ULN) or ≤ 5 X institutional upper limit of normal (ULN) in the presence of liver metastases

5. Creatinine ≤ 1.5 X institutional upper limit of normal (ULN)

• Subjects willing for repeat oral dosing and follow-up, including pharmacokinetic sampling
• Women of childbearing potential and men willing to agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, during the duration of study participation and for at least 4 weeks after withdrawal from the study, unless they are surgically sterilised
• Ability to understand and the willingness to provide a written informed consent document

Exclusion Criteria

• Subjects who have received any prior chemotherapy, radiotherapy, biologic/targeted anti-cancer therapy or surgery within 4 weeks (6 weeks for monoclonal antibodies, radioactive monoclonal antibodies or any radio- or toxin- immunoconjugates) before the first study drug administration and have not recovered (to AEs < Grade 2) from the toxic effects from any prior therapy
• Subjects having received any other investigational agents within 4 weeks prior to the first study drug administration and have not recovered completely (to AEs < Grade 2) from the side effects of the earlier investigational agent
• Subjects with documented history of diabetes mellitus except for the Diabetes Expansion Cohort
• For the Diabetes Expansion Cohort - Subjects who have type 1 diabetes mellitus, maturity onset diabetes of the young, hyperglycemia due to reasons other than type 2 diabetes mellitus.
• For the Diabetes Expansion Cohort - Subjects who currently require insulin, thiazolidinediones, dual proliferator-activated receptors (PPAR) agonists, glucagon-like peptide (GLP-1) analogues, dipeptidyl peptidase (DPP-IV) inhibitors or have received the same in the 4 weeks prior to screening.
• Subjects with known complications of diabetes like diabetic nephropathy or diabetic retinopathy
• Subjects with known brain metastases
• Subjects with gastrointestinal abnormalities including inability to take oral medication, malabsorption or other conditions like chronic inflammatory bowel disease that may affect absorption.
• Subjects with a history of myocardial infarction or uncontrolled cardiac dysfunction during the previous 6 months
• Subjects with baseline QTc interval >470 msec at screening
• Subjects on warfarin. Prophylactic anticoagulation with low molecular weight heparin is allowed
• Subjects with history of anaphylaxis or angioedema, bronchial asthma, peptic ulcer and clinically significant food or drug allergy
• Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Women who are pregnant or nursing
• Subjects with known seropositivity to human immunodeficiency virus (HIV), positive for Hepatitis B, positive for Hepatitis C (antigen positive), or known hepatic cirrhosis

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Piramal Enterprises Limited

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dr Anthony El-Khoueiry, MD

Role: PRINCIPAL_INVESTIGATOR

University of Southern California

Locations

USC Norris Comprehensive Cancer Center

Los Angeles, California, United States

Central India Cancer Research Institute

Nagpur, Maharashtra, India

Curie Manavata Cancer Centre

Nashik, Maharashtra, India

Ruby Hall Clinic

Pune, Maharashtra, India

Meenakshi Mission Hospital and Research Centre

Madurai, Tamil Nadu, India

Countries

United States; India

Other Identifiers

PL225B/71/11

Identifier Type: -

Identifier Source: org_study_id