Health Condition 1: C649- Malignant neoplasm of unspecifiedkidney, except renal pelvis
Conditions
Interventions
Intervention1: Everolimus 10 mg manufactured by Eugia Pharma Specialities Limited: The study will consist of two periods on Day 1 period I or day 15 period II based on randomization schedule patients
Sponsors
Eugia Pharma Specialities Limited
Eligibility
Inclusion criteria
Inclusion criteria: 1. Male and females of age in between 18 years to 65 years (both inclusive). 2. Ability to provide informed consent prior to participation in the study by patient/LAR 3. Confirmed diagnosis of advanced renal cell carcinoma. 4. Who are already receiving a stable dose of Everolimus tablets, 10 mg tablet once daily as per investigatorâ??s discretion for at least 14 days at first dosing of study drug. 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. 6. Estimated life expectancy >= 3 months. 7. No persistent toxicities from prior medications [Recovery to baseline or 8. Adequate organ and bone marrow function based upon the following laboratory criteria within 7 days before randomization: a. Hemoglobin >=9.0 g/dL b. Absolute neutrophil count >=1500/uL c. Platelet count >=100,000/uL d. Creatinine e. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) f. Total bilirubin within g. Clinically insignificant fasting serum glucose levels, S. blood urea nitrogen (BUN) and Urine protein levels. 9. Patient having negative urine screen for drugs of abuse 10. Patient having negative breath alcohol test 11. Sexually active women, unless surgically sterile (at least 6 months prior to study drug administration) or postmenopausal for at least 12 consecutive months, must agree to use effective methods of avoiding pregnancy from screening, during study and up to 8 weeks after the last dose of study drug. 12. Females must use acceptable and effective methods of contraception such as the following: • Tubal sterilization (tubal ligation performed more than one month before Study Day1 transcervical tubal occlusion procedure performed more than six months before Study Day 1) • Intrauterine Device (IUD) • Progestin Implant (i.e. Implanon or its equivalent) • Progestin injection or progestin oral contraceptive pill + one barrier method (cervical cap, diaphragm, contraceptive sponge, or vaginal spermicide + a male or female condom) • Two barrier methods used together (cervical cap, diaphragm contraceptive sponge, or vaginal spermicide + a male or female condom) • Absolute sexual abstinence (no sexual intercourse or genital contact with a male partner) 13. Male patient must agree to use an effective method of contraception from screening, during study and up to 8 weeks after the last dose of study drug. 14. Clinically insignificant laboratory values at screening 15. Patients willing to and able to comply with the protocol
Exclusion criteria
Exclusion criteria: 1. Known hypersensitivity to rapamycin, temsirolimus, everolimus or any excipient of everolimus. 2. Any prior treatment with everolimus resulting in unacceptable toxicity. 3. Receipt of any type of small molecule kinase inhibitors (i.e. axitinib, pazopanib, sorafenib, sunitinib etc) within 2 weeks before randomization. 4. Patients with renal failure, hepatic failure or for whom the need for dose change during the study can be anticipated. 5. Radiation therapy for bone metastasis within 2 weeks, any other external radiation therapy within 4 weeks before randomization. 6. Patients on active treatment with strong, moderate inhibitors or strong inducers of P-glycoprotein and CYP3A4[a minimal of 2 weeks or 5 half- lives wash-out period(whichever is earlier) recommended after stopping such medications]. 7. History of brain metastasis, spinal cord compression 8. Systemic treatment with radionuclides within 6 weeks before randomization or with clinically relevant persistent complications from prior radiation therapy. 9. Concomitant anticoagulation at therapeutic doses with oral anticoagulants or platelet inhibitors [Low-dose aspirin and low-dose warfarin ( 10. Uncontrolled, significant inter-current or recent illness including, but not limited to a. Cardiovascular disorders: i. Symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmias. ii. Uncontrolled hypertension defined as sustained BP 150 mm Hg systolic or > 100 mm Hg diastolic despite optimal antihypertensive treatment. iii. Stroke (including TIA), myocardial infarction, within 6 months before randomization. b. Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation: i. Active peptic ulcer disease, inflammatory bowel disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis or acute obstruction of the pancreatic or biliary duct, or gastric outlet obstruction. ii. Abdominal fistula, gastrointestinal perforation, bowel obstruction, or intra-abdominal abscess within 6 months before randomization. Clinically significant hematuria, hematemesis, or hemoptysis of half teaspoon (2.5 ml) of red blood, or other history of significant bleeding (eg, pulmonary hemorrhage) within 3 months before randomization. c. Cavitating pulmonary lesion(s) or known endobronchial disease manifestation. d. Patient with active infection and symptoms of Non-infectious pneumonitis as judged by the investigator. e. Malabsorption syndrome. f. Serious non-healing wound/ulcer/bone fracture. g. Lesions invading major pulmonary blood vessels. 11. In the past 5 years, other prior malignancy (except basal cell carcinoma, squamous cell carcinoma of the skin, or cervical carcinoma in situ). 12. Pregnant and lactating females. 13. Chronic treatment with corticosteroids or other immunosuppressive agents (with the exception of inhaled or topical corticosteroids or corticosteroids with a daily dosage equivalent 14. Positive test for hepatitis B surface antigen, hepatitis C antibody, or human immun
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| Minimum concentration over the steady state dosing interval Average concentration over the steady state dosing interval Percentage fluctuation Time of maximum measured blood concentration over the steady state dosing interval Pre dose concentrations determined before a dose at steady state Swing Safety and tolerabilityTimepoint: Venous blood samples 3mL will be withdrawn within 5 minutes prior to dosing on Day 1 12 13 and 14 Period I and Day 15 26 27 and 28 Period II to confirm steady state condition Venous blood samples 3mL will be withdrawn on Day 14 and 28 at 0.17 0.25 0.50 0.75 1 1.25 1.50 1.75 2.00 2.25 2.50 3.00 4.00 6.00 8.00 12.00 16.00 and 24.00 hours post drug administration. | — |
Primary
| Measure | Time frame |
|---|---|
| Cmax AUC0-Ï? Area under the blood concentration time curve over the steady state dosing interval Cmax ss Maximum concentration over the steady state dosing interval Timepoint: Venous blood samples 3mL will be withdrawn within 5 minutes prior to dosing on Day 1 12 13 and 14 Period I and Day 15 26 27 and 28 Period II to confirm steady state condition Venous blood samples 3mL will be withdrawn on Day 14 and 28 at 0.17 0.25 0.50 0.75 1 1.25 1.50 1.75 2.00 2.25 2.50 3.00 4.00 6.00 8.00 12.00 16.00 and 24.00 hours post drug administration. | — |
Countries
India
Contacts
Public ContactDr Subhra Lahiri
Axis Clinicals Ltd
Outcome results
None listed