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

This study is currently recruiting participants.
Verified January 2014 by Piramal Enterprises Limited
Sponsor:
Information provided by (Responsible Party):
Piramal Enterprises Limited
ClinicalTrials.gov Identifier:
NCT01779336
First received: January 28, 2013
Last updated: January 31, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Advanced Refractory Solid Tumors
Drug: PL225B
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label Multicentre Phase 1 Study of Oral IGF-1R Inhibitor PL225B in Subjects With Advanced Refractory Solid Tumors.

Resource links provided by NLM:


Further study details as provided by Piramal Enterprises Limited:

Primary Outcome Measures:
  • Maximum tolerated dose [ Time Frame: End of Cycle 1 (i.e. 21 Days) ] [ Designated as safety issue: Yes ]
    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).


Secondary Outcome Measures:
  • Number of subject with adverse events [ Time Frame: Until disease progression or unacceptable toxicity (expected to be 4-6 months) ] [ Designated as safety issue: Yes ]
    The toxic effects of the drug would be assessed from adverse events, vital signs and by clinically significant changes in the laboratory evaluations.

  • Pharmacokinetic profile(Cmax,Tmax and AUC) [ Time Frame: Until disease progression or unacceptable toxicity (expected to be 4-6 months) ] [ Designated as safety issue: No ]
    The following PK parameters will be calculated: Cmax (peak plasma concentration), Tmax (time to peak plasma concentration), AUC0-t (area under the plasma concentration curve from time zero to time of last quantifiable concentration), AUC0-12, AUC0-inf (area under the plasma concentration curve from time zero extrapolated to infinity), percent AUC extrapolated, kel (elimination rate constant), t1/2 (elimination half-life), CL/F (oral clearance), Vz/F (oral apparent volume of distribution) and Racc (accumulation ratio).

  • Activity of PL225B based on selected biomarkers [ Time Frame: Until disease progression or unacceptable toxicity (expected to be 4-6 months) ] [ Designated as safety issue: No ]
    Plasma samples will be used for analysis of circulating exploratory biomarkers which are likely to change in response to PL225B administration.

  • Objective response [ Time Frame: Until disease progression or unacceptable toxicity (expected to be 4-6 months) ] [ Designated as safety issue: No ]
    Evaluation of Response: Clinical responses will be presented patient wise for different dose levels.


Estimated Enrollment: 70
Study Start Date: December 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PL225B
Patients will receive study drug on a daily basis until disease progression or unacceptable toxicity in sequential cohorts following accelerated titration design.
Drug: 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.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01779336

Contacts
Contact: Dr Alan K Hatfield, MD +91 22 3027 5002 ext 5002 alan.hatfield@piramal.com
Contact: Dr Sandesh Sawant, MBBS +91 22 30275130 ext 5130 sandesh.sawant@piramal.com

Locations
United States, California
USC Norris Comprehensive Cancer Center Recruiting
Los Angeles, California, United States, 90033
Contact: Dr Anthony El-Khoueir, MD    323-865-3967    elkhouei@usc.edu   
Principal Investigator: Dr Anthony El-Khoueiry, MD         
India
Central India Cancer Research Institute Recruiting
Nagpur, Maharashtra, India, 440010
Contact: Dr. Ajay Mehta, MBBS, MS, UICC    91-712-2520956    ajayonco@hotmail.com   
Principal Investigator: Ajay Mehta, MBBS, MS, UICC         
Curie Manavata Cancer Centre Recruiting
Nashik, Maharashtra, India, 422004
Contact: Dr Rajnish Nagarkar    02532592666    drraj@manavatacancercentre.com   
Principal Investigator: Dr Rajnish Nagarkar         
Ruby Hall Clinic Recruiting
Pune, Maharashtra, India, 411001
Contact: Dr Minish Jain, MD    +912066455604    minishjain009@gmail.com   
Principal Investigator: Dr Minish Jain Jain         
Meenakshi Mission Hospital and Research Centre Not yet recruiting
Madurai, Tamil Nadu, India, 625107
Contact: Dr. Krishna Kumar Ratnam, MBBS, MD, DM    91-9380417299    kkratnam@gmail.com   
Principal Investigator: Dr Krishna Kumar Ratnam, MBBS, MD, DM         
Sponsors and Collaborators
Piramal Enterprises Limited
Investigators
Principal Investigator: Dr Anthony El-Khoueiry, MD University of Southern California
  More Information

No publications provided

Responsible Party: Piramal Enterprises Limited
ClinicalTrials.gov Identifier: NCT01779336     History of Changes
Other Study ID Numbers: PL225B/71/11
Study First Received: January 28, 2013
Last Updated: January 31, 2014
Health Authority: United States: Food and Drug Administration
India: Drugs Controller General of India

Keywords provided by Piramal Enterprises Limited:
Advanced Refractory Solid Tumors

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on April 17, 2014