Comparison of Paclitaxel/Carboplatin and Lonafarnib to Paclitaxel/Carboplatin for First-line Treatment of Ovarian Cancer

Study Overview
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Brief Summary
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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
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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.

Official Title
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An Open-label, Multicenter, Randomized Phase II Study to Compare the Effects of Paclitaxel/Carboplatin and Lonafarnib to Those of Paclitaxel/Carboplatin for First-line Treatment of Patients With Epithelial Ovarian Cancer FIGO Stages IIB-IV

Conditions
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Epithelial Ovarian Cancer

Intervention / Treatment
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* Drug: Lonafarnib


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lonafarnib / Paclitaxel /Carboplatin<br> | Drug: Lonafarnib<br>* 100mg/twice a day during chemotherapie,in maintenance phase 200 mg twice a day<br>|
| Other: Paclitaxel/Carboplatin<br>Standard Chemotherapy | Drug: Lonafarnib<br>* 100mg/twice a day during chemotherapie,in maintenance phase 200 mg twice a day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  | every 3 months until PD | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 |