Comparative bioavailability study of Etoposide Capsules 100 mg in adult patients with platinum resistant or refractory ovarian cancer.

Not yet recruiting

• Conditions: Malignant neoplasm of unspecifiedovary,

• Registration Number: CTRI/2022/05/042819
• Lead Sponsor: Intas Pharmaceuticals Ltd India

Brief Summary

This is a multicentric, open label, balanced, randomized, two-treatment, two-period with two consecutive profile in single period, two-sequence, crossover, multiple oral dose, comparative bioavailability study of Etoposide Capsules 100 mg (Test drug from Intas Pharmaceuticals Limited, India)  with Vepesid 100 mg (Etoposide) Soft Capsules (Reference drug from Cheplapharm Arzneimittel GmbH) in adult patients with platinum resistant or refractory ovarian cancer. A target of 58 completers has been kept in this study. The study will be conducted in 2 phases: a 10-day screening phase, and a 12-day open label intervention phase extending from Day 1 (baseline) to Day 13 (EOS). The two-periods of the study will be conducted in two consecutive cycles. There will be no wash out period between two periods. The duration of individual participation will be approximately 23 days.

Detailed Description

Not available

Study Timeline

• Study Start: 2022-05-31
• Last Update Posted: 2022-12-13

Recruitment & Eligibility

• Status: Not Yet Recruiting
• Sex: Female
• Target Recruitment: 58

Inclusion Criteria

• Participants are eligible to be included in the study only if all of the following criteria apply: 1.
• Participant must sign an ICF indicating that she understands the purpose of, and procedures required for the study as described in this protocol and is willing to participate in the study.
• Participant must be woman, aged greater than 18 years of age, at the time of signing the informed consent.
• Documented medical history of histo-pathologically or cytologically confirmed diagnosis of epithelial carcinoma of the ovary, fallopian tube cancer or primary peritoneal carcinoma.
• Documented past medical history of platinum resistant or refractory disease as per standard clinical and Gynecologic Cancer Intergroup Committee (GCIC) criteria: Platinum-resistant disease, defined as disease progression less than or equal to 6 months after completing a platinum-based regimen (3- 6 cycles).
• Platinum-refractory disease: Lack of response (CR or PR) or disease progression while receiving the platinum-based therapy.
• Participant who are already receiving and tolerating oral etoposide monotherapy at dose of 100 mg once daily as per the independent clinical judgment of the Investigator for at least one previous cycle (i.e. 21 days treatment in a 28-days cycle).
• Body mass index (BMI) within the range 18.5 – 30 kg per m2 (inclusive) at screening and baseline.
• Life expectancy of greater than or equal to 12 weeks at screening and baseline.
• Participants if have received radiotherapy (regardless of site & dose), a gap of 28 days must be maintained between the last dose of radiotherapy and baseline.
• Participant with adequate hematologic, liver and renal function at screening and/or baseline as defined in schedule of assessments.
• Bone marrow function: ANC greater or equal to 1500 per mm3 without granulocyte colony-stimulating factor support at screening and at baseline, Platelet count greater or equal to 100,000 per mm3 without transfusion at screening and at baseline, Hemoglobin greater or equal to 9 g per dL without erythropoietin dependency and without packed red blood cell transfusion at screening and at baseline.
• Renal function: Creatinine Clearance greater than 50 mL per min as calculated by Cockcroft Gault formula at screening and at baseline.
• Hepatic function: Bilirubin less than or equal to ULN at screen, ALT, AST, Alkaline phosphatase less or equal to 2.5 times ULN at screening (ALT, AST, Alkaline phosphatase less than or equal to5 times ULN will be allowed in cases where increase is related to liver metastases), Serum Albumin greater than or equal to 3 g per dL at screening.
• A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: Is not a woman of childbearing potential (WOCBP) OR Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of less than 1% per year), with low user dependency when used consistently and correctly, during the intervention period and for at least 6 months after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during the study and for a period of at least 6 months.
• The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention.
• A WOCBP must have a negative highly sensitive serum pregnancy test at screening; and urine pregnancy test before the first dose of study intervention at baseline.
• If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required.
• In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
• The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
• Willing and able to adhere to the lifestyle restrictions specified in this protocol.

Exclusion Criteria

• Any potential participant who meets any of the following criteria will be excluded from participating in the study: 1.
• History of clinically significant medical condition including but not limited to cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances; any severe, acute, or chronic medical, psychiatric or social condition; or laboratory abnormality that as per Investigators opinion may either (a) not be in the best interest of the participant (e.g., compromise the well-being), (b) interfere with the informed consent process and or with compliance with the requirements of the trial, or (c) prevent, limit, or confound the protocol-specified assessments or (d) result in the variation of absorption or metabolism of drug, i.e., ulcerative colitis, or gastrointestinal disease.
• Known allergies, hypersensitivity, or intolerance to etoposide capsules 100 mg or its excipients (refer to SmPC of Vepesid).
• Contraindications to the use of etoposide as per SmPC of Vepesid at screening and at baseline.
• Had major surgery, (e.g., requiring general anesthesia) within 4 weeks before screening, or will not have fully recovered from surgery, or has surgery planned during the time the participant is expected to participate in the study or within 30 days after the last dose of study intervention administration.
• NOTE: Participants with planned minor surgical procedures to be conducted under local anesthesia may participate.
• History of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) positive, or other clinically active liver disease, or tests positive for HBsAg or anti-HCV at screening.
• History of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV at screening.
• History of drug abuse within 1 year before screening or positive test result(s) for drugs of abuse (including barbiturates, opiates, cocaine, cannabinoids, amphetamines and benzodiazepines) at baseline with exception of drugs prescribed for medical reason.
• History of alcohol abuse within 1 year before screening or positive test result(s) for alcohol abuse at baseline.
• Lymphoma, leukemia, or any malignancy within the past 5 years from screening except for malignancy under study, basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years; carcinoma in situ of the cervix; or malignancy, which is considered cured with minimal risk of recurrence.
• Participant s unable to ingest oral medications.
• Known CNS disease at screening, except for treated asymptomatic CNS metastases, provided all of the following criteria are met: Only supratentorial metastases allowed (i.e., no metastases to midbrain, pons, medulla, or spinal cord), No evidence of interim progression or hemorrhage after completion of CNS-directed therapy, No ongoing requirement for corticosteroids as therapy for CNS disease, No stereotactic radiation within 14 days or whole-brain radiation within 28 days prior to randomization.
• Leptomeningeal disease at screening and baseline.
• Spinal cord compression not definitively treated with surgery and/or radiation, or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for greater than or equal to 4 weeks prior to baseline.
• Documented medical history of any of the following clinically significant cardiac conditions within 6 months of screening: Unstable angina, Myocardial infarction, New York Heart Association (NYHA) cardiac disease (Class II or greater), Unstable arrhythmias, Clinically significant pericardial disease, Electrocardiographic evidence of acute ischemic or active conduction system abnormalities, Any other cardiac illness that could lead to a safety risk to the participant in case of enrolment in the study.
• Participants requiring dose adjustment from 100 mg established dose during screening period.
• Received an investigational intervention (including investigational live vaccines) or used an invasive investigational medical device within 30 days or 5 half-lives prior to Baseline, whichever is longer, before signing the consent or is currently enrolled in an investigational study.
• Donation of blood (1 unit or 350 ml) within 90 days prior to receiving the first dose of study intervention for the current study.
• Uncontrolled blood pressure (BP) with or without antihypertensive medications, defined as systolic greater or equal to 140 mm Hg or diastolic greater or equal to 90 mm Hg at screening.
• Concomitant use of CYP3A4 inhibitors at baseline or participant who may require prohibited therapies defined in the protocol during the study.
• Current evidence of tumor lysis syndrome at screening.

Study & Design

• Study Type: BA/BE
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To characterize the pharmacokinetic profile and to compare bioavailability of Etoposide Capsules 100 mg relative to Vepesid 100 mg (Etoposide) soft capsules	12 days. | Following pharmacokinetic parameters will be evaluated, Primary Pharmacokinetic Parameters: Post dose on day 05, day 06 and day 11, day 12: Cmax, ss and AUC0-Tau,ss

Secondary Outcome Measures

Name	Time	Method
Safety: To compare the safety of Etoposide Capsules 100	mg relative to Vepesid 100 mg (Etoposide) soft capsules.
To evaluate the pharmacokinetic profile of Etoposide Capsules 100 mg relative to Vepesid 100 mg (etoposide) soft capsules	Day 12.

Trial Locations

Locations (20)

Chopda medicare & Research Centre, Meghnam Heart Institute; 🇮🇳 Nashik, MAHARASHTRA, India

Dept of Oncology & Radiation Therapy, GMCH; 🇮🇳 Nagpur, MAHARASHTRA, India

Erode Cancer Centre; 🇮🇳 Erode, TAMIL NADU, India

GBH Memorial Cancer Hospital; 🇮🇳 Udaipur, RAJASTHAN, India

HCG Manavata Cancer Centre; 🇮🇳 Nashik, MAHARASHTRA, India

Khandesh Cancer Centre; 🇮🇳 Surat, GUJARAT, India

King George Hospital, Andhra Medical Collage; 🇮🇳 Visakhapatnam, ANDHRA PRADESH, India

Kiran Hospital Multi Super Speciality Hospital & Research Centre; 🇮🇳 Surat, GUJARAT, India

KLES Dr. Prabhakar Kore Hospital & MRC; 🇮🇳 Belgaum, KARNATAKA, India

Kolhapur Cancer Centre Pvt. Ltd; 🇮🇳 Kolhapur, MAHARASHTRA, India

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Chopda medicare & Research Centre, Meghnam Heart Institute

🇮🇳Nashik, MAHARASHTRA, India

Dr Mangesh Korde

Principal investigator

9028532380

drmangeshkorde@yahoo.in