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An Open Label Multicentre Phase 1 Study of Oral IGF-1R Inhibitor PL225B in Subjects With Advanced Refractory Solid Tumors.


Phase 1
18 Years
90 Years
Open (Enrolling)
Both
Advanced Refractory Solid Tumors

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Trial Information

An Open Label Multicentre Phase 1 Study of Oral IGF-1R Inhibitor PL225B in Subjects With Advanced Refractory Solid Tumors.


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.


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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose

Outcome Description:

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).

Outcome Time Frame:

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

Safety Issue:

Yes

Principal Investigator

Dr Anthony El-Khoueiry, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

USC/Norris Comprehensive Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

PL225B/71/11

NCT ID:

NCT01779336

Start Date:

December 2012

Completion Date:

December 2014

Related Keywords:

  • Advanced Refractory Solid Tumors
  • Advanced Refractory Solid Tumors
  • Neoplasms

Name

Location

USC Norris Comprehensive Cancer CenterLos Angeles, California  90089