Epithelial Ovarian Cancer
Conditions
Brief summary
The purpose of this study is to compare the effects of Paclitaxel/Carboplatin and Lonafarnib to those of Paclitaxel/Carboplatin in primary treatment of patients with epithelial ovarian cancer.
Detailed description
Today the standard therapy for patients with advanced ovarian carcinoma is paclitaxel and carboplatin. Lonafarnib is a farnesyl transferase inhibitor (FTI) that is active against a broad spectrum of tumor cell lines in vitro and tumor xenografts in nude mice. Lonafarnib has single-agent antitumor activity as well as enhanced activity in combination with taxanes in a number of tumor cell lines and in vivo models.
Interventions
DRUGLonafarnib
100mg/twice a day during chemotherapie,in maintenance phase 200 mg twice a day
Sponsors
AGO Study Group
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Previously untreated patients with a histologically confirmed diagnosis of cancer of the ovary, the fallopian tube or extra-ovarian papillary serous tumors FIGO stage IIB-IV, regardless of measurable or non-measurable disease * Age \>= 18 years * ECOG performance status \<= 2 * Life-expectancy of at least 6 months * Adequate bone marrow, renal and hepatic function: WBC \>= 3.0 x 10\^9/l; Neutrophils (ANC) \>= 1.5 x 10\^9/l; Platelets \>= 100 x 10\^9/l; Hemoglobin \> 6 mmol/l (\> 10.0 g/dl); Bilirubin \<= 1 x upper limit of normal range; Alkaline phosphatase \<= 2.5 x upper limit of normal range; estimated GFR \>= 50 ml/min according to Jelliffe or Cockroft-Gault formula * Patients who have given their signed and written informed consent to participate in the trial after fully understanding the implication and constraints of the protocol * Patients must be geographically accessible for treatment and follow-up * Time between definitive surgery and randomization into the study \<= 6 weeks
Exclusion criteria
* Ovarian tumors of low malignant potential (borderline tumors) * Non-epithelial ovarian or mixed epithelial/nonepithelial tumors (e.g. Mixed Mullerian tumors) * Patients who have received previous chemotherapy or radiotherapy * Prior treatment with FT inhibitors * Patients with a prior diagnosis of any malignancy not cured by surgery alone less than 5 years before study entry (except in situ carcinoma of the cervix or adequately treated basal cell carcinoma of the skin) * Complete bowel obstruction or the presence of symptomatic brain metastases * Concurrent severe medical problems unrelated to malignancy which would significantly limit full compliance with the study or expose the patient to extreme risk or decreased life expectancy * Patients with a history of seizure disorder or central nervous system disorders; pre-existing motor or sensory neurologic pathology or symptoms \> NCI grade 1 * History of congestive heart failure (NYHA Classification \> 2, even if medically controlled. * History of clinical and electrocardiographically documented myocardial infarction within the last 6 months. * History of atrial or ventricular arrhythmias (\>= LOWN II) * Patients with significant Fridericia QTc (QTcF) prolongation at Baseline (ie. QTcF \>= 470 msec) * Patients with severe active infection * Patients with a history of severe hypersensitivity reactions to products containing Cremophor EL (cyclosporin or vitamin K) and/or patients with known hypersensitivity to compounds chemically related to Carboplatin and Paclitaxel * Women with childbearing potential and who are sexually active and unwilling to use a medically acceptable method of contraception (oral contraceptive, diaphragm with spermicide, intrauterine device, condom with spermicide) * Women who are pregnant or breast feeding * Administration of other anticancer therapy or simultaneous chemotherapeutic and/or hormonal drugs, or radiotherapy during the study treatment period (except: hormonal replacement therapy and/or steroid antiemetics) * Patients who are participating in any other clinical study * Dementia or significantly altered mental status that would prohibit the understanding and giving of informed consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-free survival | every 3 months until PD |
Secondary
| Measure | Time frame |
|---|---|
| Objective tumor response rate (CR/PR (RECIST)) | During whole trial |
| Duration of response | Until Progression of disease |
| Overall survival | Until date of death |
| safety based on nature, frequency and severity of adverse events | During treatment phase until resolution |
| Predose lonafarnib concentrations | During treatment |
| PD activity | Assessment |
Countries
Germany
Outcome results
None listed