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

This study is currently recruiting participants. (see Contacts and Locations)
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 July 20, 2014