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

AGO Study Group

Status and phase

Completed

Phase 2

Conditions

Epithelial Ovarian Cancer

Treatments

Drug: Lonafarnib

Study type

Interventional

Funder types

Other

Identifiers

NCT00281515

AGO-OVAR 15

Details and patient eligibility

About

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.

Full 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.

Enrollment

105 patients

Sex

Female

Ages

18+ years old

Volunteers

No Healthy Volunteers

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