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
| ISRCTN | ISRCTN51315091 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN51315091 |
| Secondary identifying numbers | AGO-OVAR 15 |
- Submission date
- 12/07/2005
- Registration date
- 23/08/2005
- Last edited
- 02/07/2012
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Not provided at time of registration
Contact information
Mrs Gabriele Elser
Scientific
Scientific
Ludwig-Erhard-Str. 100
Wiesbaden
65199
Germany
Study information
| Study design | Randomised controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Multi-centre |
| Study setting(s) | Not specified |
| Study type | Treatment |
| Scientific title | |
| Study acronym | AGO-OVAR 15 |
| Study objectives | Standard chemotherapy for ovarian cancer patients after primary cytoreductive surgery is paclitaxel in combination with carboplatin. Several phase III studies are evaluating the efficacy of a third drug within this standard trial either as a combined or as a consolidation therapy. The final results of these studies have not yet been published. The addition of farnesyltransferase (FT) inhibitors or epidermal growth factor inhibitors to primary chemotherapy are very promising approaches to optimize primary therapy. Lonafarnib is a FT inhibitor 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 mice models. Based upon positive results from clinical studies demonstrating enhanced activity when combining taxanes with lonafarnib, combination therapy of paclitaxel and carboplatin with lonafarnib is expected to have greater efficacy than standard therapy or FTI therapy alone in primary ovarian cancer patients. |
| Ethics approval(s) | Not provided at time of registration |
| Health condition(s) or problem(s) studied | Epithelial Ovarian Cancer, First-Line Treatment |
| Intervention | Paclitaxel/Carboplatin +/- Lonafarnib The previous sponsor for this trial (until November 2009) was: MedServ. GmbH (Germany) Ludwig-Erhard-Str. 100, 65199 Wiesbaden Germany |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Paclitaxel/Carboplatin and Lonafarnib |
| Primary outcome measure | 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 IIBIV. 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 | 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. |
| Overall study start date | 01/09/2005 |
| Completion date | 30/09/2006 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 100 |
| Key inclusion criteria | 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 IIBIV 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 |
| Key exclusion criteria | 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 |
| Date of first enrolment | 01/09/2005 |
| Date of final enrolment | 30/09/2006 |
Locations
Countries of recruitment
- Germany
Study participating centre
Ludwig-Erhard-Str. 100
Wiesbaden
65199
Germany
65199
Germany
Sponsor information
AGO Research GmbH (Germany)
Industry
Industry
Kaiser-Friedrich-Ring 71
Wiesbaden
65185
Germany
| Website | http://www.ago-ovar.de |
|---|---|
"ROR" |
https://ror.org/01jdhsq12 |
Funders
Funder type
Charity
AGO Ovarian Cancer Study Group (AGO-OVAR)
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/08/2012 | Yes | No |
