An open-label, multicenter, randomized Phase II Study to compare the effects of Paclitaxel/Carboplatin and Lonafarnib to those of Paclitaxel/Carboplatin for 1st line Treatment of patients with epithelial ovarian cancer International Federation of Gynecology and Obstetrics (FIGO) Stages IIB-IV
- Conditions
- Epithelial Ovarian Cancer, First-Line TreatmentCancerOvarian
- Registration Number
- ISRCTN51315091
- Lead Sponsor
- AGO Research GmbH (Germany)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 100
1. Previously untreated patients with a histologically confirmed diagnosis of cancer of the ovary or the fallopian tube or extra-ovarian papillary serous tumors
FIGO stage IIB?IV regardless of measurable or non-measurable disease
2. Age =18 years
3. Eastern Cooperative Oncology Group (ECOG) performance status =2
4. Life-expectancy of at least 6 months
5. Adequate bone marrow, renal and hepatic function defined as
white blood cell count (WBC) >3.0/nl, Neutrophils (ANC) =1.5/nl, Platelets =100/nl, Hemoglobin >6 mmol/l (>10.0 g/dl), Bilirubin =1 x upper limit of normal range
6. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <1.5 x upper limit of normal range
7. Alkaline phosphatase <2.5 x upper limit of normal range
8. Estimated glomerular filtration rate GFR =50 ml/min according to Jelliffe or Cockroft-Gault formula
9. 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
10. Patients must be geographically accessible for treatment and follow-up
11. Time between definitive surgery and randomization =6 weeks
1. Ovarian tumors of low malignant potential (borderline tumors
2. Non-epithelial ovarian or mixed epithelial/non epithelial tumors (e.g. mixed Mullerian tumors)
3. Patients who have received previous chemotherapy or radiotherapy
4. Prior treatment with FT inhibitors
5. 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)
6. Complete bowel obstruction or the presence of symptomatic brain metastases
7. 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
8. Patients with a history of seizure disorder or central nervous system disorders
9. Pre-existing motor or sensory neurologic pathology or symptoms >National Cancer Institute - Common Toxicity Criteria (NCI-CTC) grade 1
10. History of congestive heart failure (New York Heart Association [NYHA] Classification >2), even if medically controlled
11. History of clinical and electrocardiographically documented myocardial infarction within the last 6 months
12. History of atrial or ventricular arrhythmias (=LOWN II)
13. Patients with significant Fridericia QTc (QTcF) prolongation at Baseline (i.e. QTcF >470 msec)
14. Patients with severe active infection
15. 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
16. Fertile women not using adequate contraceptive methods
17. Women who are pregnant or breast feeding
18. 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)
19. Patients who have used any investigational drugs within 30 days of study entry
20. Patients who are participating in any other clinical study
21. Dementia or significantly altered mental status that would prohibit the understanding and giving of informed consent
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Comparison of the effect (progression-free survival [PFS]) of paclitaxel/carboplatin and lonafarnib to that of paclitaxel/carboplatin in patients with previously untreated epithelial cancer of the ovary FIGO stages IIB?IV. The primary purpose of this study is to determine whether the additional effect of lonafarnib is sufficient to conduct a phase III study.
- Secondary Outcome Measures
Name Time Method The secondary objectives are to evaluate response to treatment and overall survival, and to assess the safety in both treatment arms and to assess exposure (PK) and PD of lonafarnib.