Health Condition 1: null- Advanced refractory solid tumors
Conditions
Interventions
Intervention1: PL225B: Study drug will be administered once daily for 21 days. PL225B will be administered orally in the form of tablet(s) once daily.
Control Intervention1: NIL: NIL
Sponsors
Piramal Enterprises Limited
Eligibility
Inclusion criteria
Inclusion criteria: 1. 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 2. Subjects should have measurable or evaluable disease 3. Subjects of either sex, of all races and ethnic groups, and more than equal to 18 years of age 4. ECOG (Eastern Cooperative Oncology Group) performance status 0-1 5. Subjects with life expectancy of at least 4 months 6. Subjects with fasting plasma glucose less than equal to 125 mg/dl and HbA1c less than 6.5 % at screening Subjects with fasting plasma glucose less than equal to 150 mg/dL and HbA1c less than equal to 7.0 % at screening for the Diabetes Expansion Cohort 7. 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. 8. Subjects willing for repeat oral dosing and follow-up, including pharmacokinetic sampling 9. 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 10. Ability to understand and the willingness to provide a written informed consent document
Exclusion criteria
Exclusion criteria: 1. 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 less than equal to Grade 2) from the toxic effects from any prior therapy 2. Subjects having received any other investigational agents within 4 weeks prior to the first study drug administration and have not recovered completely (to AEs less than equal to Grade 2) from the side effects of the earlier investigational agent 3. Subjects with documented history of diabetes mellitus except for the Diabetes Expansion Cohort 4. For the Diabetes Expansion Cohort â?? Subjects who have type 1 diabetes mellitus, maturity onset diabetes of the young, hyperglycemia due to reasons other than type 2 diabetes mellitus 5. 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 6. Subjects with known complications of diabetes like diabetic nephropathy or diabetic retinopathy 7. Subjects with known brain metastases 8. Subjects with gastro intestinal abnormalities including inability to take oral medication, malabsorption or other conditions like chronic inflammatory bowel disease that may affect absorption 9. Subjects with a history of myocardial infarction or uncontrolled cardiac dysfunction during the previous 6 months 10. Subjects on warfarin. Prophylactic anticoagulation with low molecular weight heparin is allowed. 11. Subjects with history of anaphylaxis or angio-edema, bronchial asthma, peptic ulcer and clinically significant food or drug allergy 12. Subjects with uncontrolled inter-current 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 13. Women who are pregnant or nursing
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To determine the maximum tolerated dose and dose limiting toxicity (ies).Timepoint: 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. This 21 day administration will define a treatment cycle. Subjects may receive consecutive treatment cycles until evidence of disease progression, intolerance of therapy, or withdrawal from the protocol as specified | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. To characterize the safety profile of PL225B 2. To characterize the pharmacokinetic profile of PL225B 3. To evaluate activity of PL225B based on effect on selected biomarkers 4. To evaluate efficacy of PL225B based on objective response 5. To evaluate the safety, tolerability, pharmacokinetics and efficacy of PL225B in subjects of advanced refractory solid tumors with type 2 diabetes mellitus in a Diabetes Expansion Cohort Timepoint: 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. This 21 day administration will define a treatment cycle. Subjects may receive consecutive treatment cycles until evidence of disease progression, intolerance of therapy, or withdrawal from the protocol as specified | — |
Countries
India
Contacts
Public ContactDr Sanjeev C Hegde
Piramal Enterprises Limited
Outcome results
None listed