Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
AGO-OVAR 15
Study information
Scientific title
Acronym
AGO-OVAR 15
Study hypothesis
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
Not provided at time of registration
Study design
Randomised controlled trial
Primary study design
Interventional
Secondary study design
Multi-centre
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Condition
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
Phase
Phase II
Drug names
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 trial start date
01/09/2005
Overall trial end date
30/09/2006
Reason abandoned (if study stopped)
Eligibility
Participant 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
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
100
Participant 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
Recruitment start date
01/09/2005
Recruitment end date
30/09/2006
Locations
Countries of recruitment
Germany
Trial participating centre
Ludwig-Erhard-Str. 100
Wiesbaden
65199
Germany
Sponsor information
Organisation
AGO Research GmbH (Germany)
Sponsor details
Kaiser-Friedrich-Ring 71
Wiesbaden
65185
Germany
Sponsor type
Industry
Website
Funders
Funder type
Charity
Funder name
AGO Ovarian Cancer Study Group (AGO-OVAR)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2012 results http://www.ncbi.nlm.nih.gov/pubmed/22564713
Publication citations
-
Results
Meier W, du Bois A, Rau J, Gropp-Meier M, Baumann K, Huober J, Wollschlaeger K, Kreienberg R, Canzler U, Schmalfeldt B, Wimberger P, Richter B, Schröder W, Belau A, Stähle A, Burges A, Sehouli J, Randomized phase II trial of carboplatin and paclitaxel with or without lonafarnib in first-line treatment of epithelial ovarian cancer stage IIB-IV., Gynecol. Oncol., 2012, 126, 2, 236-240, doi: 10.1016/j.ygyno.2012.04.050.