Clinical trial NCT00281515: Comparison of Paclitaxel/Carboplatin and Lonafarnib to Paclitaxel/Carboplatin for First-line Treatment of Ovarian Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Epithelial Ovarian Cancer
Lead sponsor: AGO Study Group
Sponsor class: OTHER
First posted: 2006-01-25
Enrollment: 105
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression-free survival
timeFrame: every 3 months until PD
Secondary outcomes:
measure: Objective tumor response rate (CR/PR (RECIST))
timeFrame: During whole trial
measure: Duration of response
timeFrame: Until Progression of disease
measure: Overall survival
timeFrame: Until date of death
measure: safety based on nature, frequency and severity of adverse events
timeFrame: During treatment phase until resolution
measure: Predose lonafarnib concentrations
timeFrame: During treatment
measure: PD activity
timeFrame: Assessment
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum, Klinik für Frauenheilkunde
city: Bremen
country: Germany
facility: Klinikum Bremen Mitte, Frauenklinik
city: Dresden
country: Germany
facility: Carl-Gustav-Carus der TU Dresden, Universitäts-Frauenklinik
city: Düsseldorf
country: Germany
facility: Ev. Krankenhaus, Frauenklinik
city: Erlangen
country: Germany
facility: Klinik für Frauenheilkunde der Univ. Erlangen
city: Essen
country: Germany
facility: Universitätsfrauenklinik
city: Frankfurt
country: Germany
facility: Klinikum der Johann Wolfgang Goethe Universität, Klinik für Frauenheilkunde u. Geburtshilfe
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg, Frauenklinik
city: Gifhorn
country: Germany
facility: Kreiskrankenhaus, Frauenklinik
city: Greifswald
country: Germany
facility: Klinik u. Poliklinik für Gynäkologie und Geburtshilfe
city: Hannover
country: Germany
facility: Medizinische Hochschule
city: Karlsruhe
country: Germany
facility: St. Vincentius-Krankenhäuser
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein, Campus Kiel, Klinik für Gynäkologie und Geburtshilfe
city: Magdeburg
country: Germany
facility: Klinik der Otto-von-Guericke Universität, Frauenklinik
city: Mainz
country: Germany
facility: Johannes-Gutenberg-Universität, Universitäts-Frauenklinik
city: Marburg
country: Germany
facility: Klinikum der Philipps-Universität Marburg, Klinik für Gynäkologie, Gynäkologische Endokrinologie
city: München
country: Germany
facility: Klinikum Großhadern, Frauenklinik
city: München
country: Germany
facility: Klinikum rechts der Isar der TU München
city: Radebeul
country: Germany
facility: Elblandkliniken, Frauenklinik
city: Rostock
country: Germany
facility: Klinikum Südstadt
city: Tübingen
country: Germany
facility: Universitäts-Frauenklinik
city: Ulm
country: Germany
facility: Universitätsfrauenklinik
city: Wiesbaden
country: Germany
facility: Dr. Horst Schmidt Klinik, Gynäkologie u. Gynäkologische Onkologie
Study officials:
affiliation: Ev. Krankenhaus, Düsseldorf, Germany
name: Werner Meier, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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, Schroder W, Belau A, Stahle 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 Aug;126(2):236-40. doi: 10.1016/j.ygyno.2012.04.050. Epub 2012 May 4.