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

NCT01779336 | Suspended Phase 1

• 1 other identifier: PL225B/71/11
• Study Type: interventional
• Target: 70
• Locations: 2 countries
• Sites: 5

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.

Conditions

Advanced Refractory Solid Tumors

Keywords

Advanced Refractory Solid Tumors

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose

  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).

  End of Cycle 1 (i.e. 21 Days)

Secondary Outcomes (4)

• Number of subject with adverse events

  Until disease progression or unacceptable toxicity (expected to be 4-6 months)

• Pharmacokinetic profile(Cmax,Tmax and AUC)

  Until disease progression or unacceptable toxicity (expected to be 4-6 months)

• Activity of PL225B based on selected biomarkers

  Until disease progression or unacceptable toxicity (expected to be 4-6 months)

• Objective response

  Until disease progression or unacceptable toxicity (expected to be 4-6 months)

Study Arms (1)

PL225B

EXPERIMENTAL

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

Drug: PL225B

Interventions

PL225B 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.

PL225B

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Absolute neutrophil count ≥ 1500/cmm
• Platelets ≥ 100,000/cmm
• Total bilirubinwithin normal limits of the institution
• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Piramal Enterprises Limited: lead

Study Sites (5)

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Central India Cancer Research Institute

Nagpur, Maharashtra, 440010, India

Location

Curie Manavata Cancer Centre

Nashik, Maharashtra, 422004, India

Location

Ruby Hall Clinic

Pune, Maharashtra, 411001, India

Location

Meenakshi Mission Hospital and Research Centre

Madurai, Tamil Nadu, 625107, India

Location

Study Officials

• Dr Anthony El-Khoueiry, MD

  University of Southern California

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2013
• First Posted: January 30, 2013
• Study Start: December 1, 2012
• Primary Completion: November 1, 2014
• Study Completion: December 1, 2014
• Last Updated: September 29, 2014

Record last verified: 2014-09

Locations

US (1); IN (4)