Clinical Study of Oral PI3K/mTOR Inhibitor in Patients With Advanced Refractory Solid Tumors

Inclusion Criteria

• Patients having histologically and/or cytologically confirmed non-haematological malignancy that is metastatic or unresectable and for which standard curative/palliative treatment does not exist or is no longer effective or is not tolerated by patient.
• Patients of either sex, of all races and ethnic groups, and more than 18 years of age.
• ECOG (Eastern Cooperative Oncology Group) performance status less than 2.
• Patients with life expectancy of at least 4 months.
• Patients with measurable or evaluable disease per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1.
• Patients must have adequate organ and marrow function as defined below:
• Absolute neutrophil count more than equal to 1500/cmm
• Platelets more than equal 100,000/cmm
• Total bilirubin within normal limits of the institution.
• AST/ALT less than equal 2.5 X institutional upper limit of normal (ULN) or less than equal 5 X institutional upper limit of normal (ULN) in the presence of liver metastases
• Creatinine less than equal 1.5 X institutional upper limit of normal (ULN)
• 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

• Patients who have received any prior chemotherapy, radiotherapy, biologic/targeted anti-cancer therapy or surgery within 4 weeks (3 months for monoclonal antibodies, radioactive monoclonal antibodies or any radio- or toxin- immunoconjugates) before study drug administration and have not recovered (to < Grade 1) from the toxic effects from any prior therapy.
• Patients having received any other investigational agents within 4 weeks prior to the date of enrolment and have not recovered completely (to < Grade 1) from the side effects of the earlier investigational agent.
• Patients with known brain metastases (except for patients who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for two months prior to first dose of study drug.)
• Patients with a history of myocardial infarction or uncontrolled cardiac dysfunction during the previous 6 months.
• Patients with diabetes mellitus requiring insulin therapy at screening or patients with clinically significant diabetic complications, such as neuropathy, retinopathy, peripheral vascular disease or nephropathy.
• Clinically significant medical condition of malabsorption, inflammatory bowel disease, or chronic diarrheal condition that might affect the absorption of the investigational agent.
• Patients on chronic anticoagulation treatment. Prophylactic anticoagulation with low-molecular heparin is allowed.
• Patients with inter-current illness including, but not limited to ongoing or clinically significant active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Patients with a known history of allergic reaction to any other medication considered to be clinically significant by the investigator.
• Women who are pregnant or nursing.
• Patients with immune deficiency and at increased risk of lethal infections, for example, known h/o HIV, HBV or HCV.