Evaluation of efficacy and safety of Paclitaxel Lipid Suspension for Injection in patients with recurrent metastatic ovarian carcinoma
- Conditions
- Health Condition 1: C569- Malignant neoplasm of unspecifiedovary
- Registration Number
- CTRI/2020/09/028042
- Lead Sponsor
- Intas Pharmaceuticals Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 0
1.The patient willing to give written signed and dated informed consent to participate in the study.
2.Female more than or equal to 18 years of age fulfilling all other eligibility criteria.
3.Patient must have histopathologically/cytologically confirmed diagnosis of epithelial carcinoma of the ovary, fallopian tube cancer or primary peritoneal high-grade serous carcinoma. Non epithelial or mixed epithelial/non-epithelial tumors (including malignant mixed Müllerian tumors), ovarian tumors with low malignant potential (borderline tumors), endometrioid, clear cell, mucinous or low-grade serous carcinomas or not otherwise specified (NOS) ovarian tumors are excluded.
4.Platinum resistant or refractory disease as per standard clinical and Gynecologic Oncology Group definition. Platinum-resistant/refractory disease, defined as disease progression within 6 months following the last administered dose of platinum therapy (resistant), or lack of response or disease progression while receiving the most recent platinum-based therapy (refractory), respectively. Progression due to rising CA125 only is not considered as platinum-resistant disease. Disease progression may be either radiographic progression or documented clinical progression.
5.Patients must have received at least one-prior platinum-based chemotherapy regimen, to include cisplatin, carboplatin or other organoplatinum compound, for treatment of primary or recurrent ovarian, fallopian tube or primary peritoneal cancer
6.Patients must have measurable or evaluable (i.e. positive serum Cancer Antigen (CA) -125 marker) disease.
7.Have at least one measurable lesion as per the RECIST criteria (version 1.1).
8.Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 1.
9.Left Ventricular Ejection fraction (LVEF) more than or equal to 50% as per Echocardiography (ECHO).
10.Patient must have recovered from any toxic effects of previous chemotherapy or radiotherapy as judged by the Investigator.
11.Previous chemotherapy/radiotherapy/surgery should be completed 4 weeks prior to start of Paclitaxel Lipid Suspension for Injection administration.
12.Patients with life expectancy of at least 6 months in the Investigatorâ??s opinion.
13.Serum pregnancy test at screening and urine pregnancy test on Day 1 (before randomization) must be negative.
14.Sexually active women, unless surgically sterile (at least 6 months prior to Study drug administration) or postmenopausal for at least 12 consecutive months, must use an effective method of avoiding pregnancy (including oral, transdermal, or implanted contraceptives [any hormonal method in conjunction with a secondary method], intrauterine device, female condom with spermicide, diaphragm with spermicide, absolute sexual abstinence, use of condom with spermicide by sexual partner or sterile [at least 6 months prior to Study drug administration] sexual partner) for at least 4 weeks prior to study drug administration, during study and up to 30 days after the last dose of study drug. Cessation of birth control after this point should be discussed with a responsible physician.
(It is the Investigatorâ??s responsibility to ensure that the above points regarding an effective method of avoiding pregnancy are discussed with patient in detail and the patient has agreed. It should be documented in the source document. The Investigato
1. Have previously received paclitaxel at any time in the platinum-resistant setting.
2. Patient who are candidate of debulking surgery, or in whom chemotherapy is planned to shrink the otherwise inoperable tumor and make it operable even if the intent is palliative.
3. Patients who are candidates to receive PARP inhibitors based on BRCA positivity and HRD status and as per its approved indication as mentioned below will be excluded.
a) Olaparib: use in women with recurrent ovarian cancer associated with a germline BRCA mutation as single-agent therapy after three or more prior lines of treatment. Relapse may be either platinum sensitive or platinum resistant.
b) Rucaparib: use in women with recurrent ovarian cancer and a known BRCA mutation (either germline or somatic) after at least two prior lines of treatment. Relapse may be either platinum sensitive or platinum resistant.
Niraparib: treatment of advanced ovarian cancer that has been treated with three or more prior chemotherapy regimens and is associated with homologous recombination deficiency-positive status, defined by either 1) a deleterious or suspected deleterious BRCA mutation, or 2) genomic instability, with progression more than six months after response to the last platinum-based chemotherapy. Genomic instability is identified by the FDA-approved companion diagnostic test for Niraparib based on the presence of three biomarkers: loss of heterozygosity, telomeric allelic imbalance, and large-scale state transitions.
Note: BRCA and HRD status will be based on history of documented testing and patients will not be screened for BRCA and HRD testing before randomization.
4. Patients who are using known substrates of CYP2C8 (i.e., repaglinide and rosiglitazone), inhibitors (i.e., gemfibrozil), and inducers (i.e., rifampin).
5. Patients who will receive Bevacizumab for their disease management will also be excluded.
6. Any of the following cardiac conditions:
6a. Unstable angina
6b. Myocardial infarction within the past 6 months
6c. Severe uncontrolled ventricular arrhythmias
6d. Clinically significant pericardial disease
6e. Electrocardiographic evidence of acute ischemia
6f. Patient with evidence of abnormal cardiac conduction (e.g., bundle branch block or heart block) except in whom the disease has been stable for the past six months
6g. History of cardiac disease that met the NYHA Classification class 2 or greater
6h. Cerebrovascular accident, transient ischemic attack or symptomatic pulmonary embolism within the past six months
7. Uncontrolled diabetes (defined as HbA1c more than or equal to 8% as per ADA) or has an active infection requiring systemic therapy.
8. History of drug or alcohol abuse according to Diagnostic and Statistical Manual of Mental Disorders (5th edition) - DSM V- criteria within 1 year before Screening or positive test result(s) for alcohol or drugs of abuse (including barbiturates, opiates, cocaine, cannabinoids, amphetamines and benzodiazepines) at Screening.
9. Has known active central nervous system metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To evaluate the efficacy of Test product (Paclitaxel Lipid Suspension for Injection) at the dose of 175 mg/m2 administered every 3 weeks, 80 mg/m2 and 60 mg/m2 every week, respectivelyTimepoint: At the end of 6 cycle (i.e. day 127(plus 2)) for 175 mg/m2 administered every 3 weeks whereas, 18 cycles (i.e. day 163(plus 2)) for 80 mg/m2 and 60 mg/m2 weekly dose.
- Secondary Outcome Measures
Name Time Method To study pharmacokinetic parameters of increasing dosages <br/ ><br>To evaluate safety of the patients who are exposed to the test product <br/ ><br>To explore dose response relationship on efficacy of different dosesTimepoint: 1.From baseline to end of the study/ 3weekly schedule-day 131-141, weekly schedule-day 180-190 <br/ ><br>2.End of treatment- 3 weekly schedule at the end of 6 cycle i.e. day 127(plus 2), weekly schedule at the end of 18 cycles i.e. day 163(plus 2). At EOS only in case of early withdrawal/discontinuation before end of treatment visit. <br/ ><br>3.From baseline to end of the treatment/ last IMP administration