Patients with a histologic diagnosis of FIGO Stage IIB, IIC, III, or IV advanced invasive epithelial ovarian, fallopian tube, or peritoneal carcinoma. MedDRA version: 8.1 Level: LLT Classification code 10033130 Term: Ovarian cancer NOS
Conditions
Interventions
Product Name: Enzastaurin
Product Code: LY317615
Pharmaceutical Form: Tablet
INN or Proposed INN: Enzastaurin Hydrochloride
Concentration unit: mg milligram(s)
Concentration type: up to
Concentration
Sponsors
Eli Lilly and Company limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - present with a histologic diagnosis of FIGO Stage IIB, IIC, III, or IV advanced invasive epithelial ovarian, fallopian tube, or peritoneal carcinoma. - should be primarily optimal debulked (0 cm residual tumor) or sub-optimal debulked (>0 cm residual tumor). - must be enrolled within six weeks after laparotomy, but should not start treatment with chemotherapy or enzastaurin/placebo earlier than 3 weeks; and have recovered from surgery sufficiently to start study therapy. - are women, who are at least 18 years of age. - have an ECOG performance status of 0, 1, or 2. - have adequate organ function including the following: Adequate bone marrow reserve and Hepatic and Renal functioning. - signed informed consent - Reproductive potential of women must be surgically sterile, postmenopausal, or compliant with a medically approved contraceptive regimen (for example, intrauterine device, birth control pills, or barrier device) during and for 6 months after the treatment period; women with reproductive potential must have a negative serum or urine pregnancy test within 3 days before study enrollment and must not be breast-feeding. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry. - receive concurrent administration of any other systemic anticancer therapy. Receive simultaneous administration of hormonal therapy during the study treatment period (hormone replacement therapy is allowed, as are steroid antiemetics). - receive concurrent radiation therapy during the study treatment period. - patients with a history of hypersensitivity reactions to products containing Cremophor EL (cyclosporine, castor oil, or vitamin K) and/or patients with known hypersensitivity to compounds chemically related to carboplatin, paclitaxel, or enzastaurin. - are unable to discontinue concurrent administration of carbamazepine, phenobarbital, or phenytoin at least 14 days prior to study therapy. - have an active infection, including active bacterial, fungal, or viral infection (at the discretion of the investigator), as well as other serious concomitant systemic disorders (for example, active infection including HIV, or cardiac disease) that, in the opinion of the investigator, would compromise the patient’s ability to adhere to the protocol. - have a serious cardiac condition, such as myocardial infarction within 6 months, angina, or heart disease, as defined by the New York Heart Association Class III or IV. Patients with a QTc prolongation >470msec and patients who have a congenital long-QT-syndrome in their own or family medical history should be excluded. - have a second primary malignancy (except adequately treated basal cell carcinoma of the skin) or a prior diagnosis of any malignancy less than 5 years before study entry (except in situ carcinoma of the cervix or adequately treated basal cell carcinoma of the skin). - have a history of central nervous system (CNS) disorder or metastases (unless the patient has completed successful local therapy for CNS metastases and has been off corticosteroids for at least 4 weeks before starting study therapy). A screening computed tomography (CT) or magnetic resonance imaging (MRI) before enrollment in the absence of a clinical suspicion of brain metastases is not required. - Are unable to swallow tablets. - are pregnant, breast feeding, or not using adequate contraceptive methods to prevent pregnancy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to compare the antitumor activity in first-line therapy of paclitaxel- and carboplatin-combination therapy plus enzastaurin followed by enzastaurin maintenance therapy (Regimen A), versus paclitaxel- and carboplatin-combination therapy plus placebo followed by placebo as a maintenance (Regimen B), as measured by progression-free survival (PFS), in patients with advanced ovarian cancer (FIGO Stage IIB-IV ovarian, fallopian tube or peritoneal epithelial carcinoma).;Secondary Objective: • to compare the response rates (RR) according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria and CA-125 according to GCIG criteria between Regimen A and Regimen B: Rate of complete response (CR), partial response (PR), and stable disease (SD) • to compare safety and adverse event profiles (including the Common Terminology Criteria for Adverse Events [CTCAE Version 3.0, NCI 2003] grades for laboratory and nonlaboratory AEs, between Regimen A and Regimen B • to evaluate the pharmacogenomics and biological markers for enzastaurin (for example: PKCß, GSK-3ß, PI3K/AKT, S6K) and the effect of enzastaurin on these molecular markers compared to patients receiving placebo • to determine if enzastaurin alters carboplatin and paclitaxel pharmacokinetics (PK) when administered in combination • to characterize the PK of enzastaurin using intensive sampling in Part 1 (safety lead-in) and sparse sampling in the randomized Part 2 of trial. ;Primary end point(s): At the time of Protocol Amendment S019(b) being implemented, 142 patients were randomized in a 1:1 fashion. Given the status of the data and that the change of the primary endpoint would lead to a more robust and informative analysis, the primary endpoint will be changed from the PFS rate at 18 months to the estimate of PFS. The original hypothesis stated an increase from 50% to 60% at 18 months was translated into an over 36% increase in the median time from 18 to 24.4 months. So, u | — |
Countries
Belgium, Germany, Spain
Outcome results
None listed