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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00281515
Recruitment Status : Completed
First Posted : January 25, 2006
Last Update Posted : June 29, 2012
Information provided by (Responsible Party):
AGO Study Group

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.

Condition or disease Intervention/treatment Phase
Epithelial Ovarian Cancer Drug: Lonafarnib Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 105 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : January 2006
Actual Primary Completion Date : December 2011
Actual Study Completion Date : December 2011

Arm Intervention/treatment
Experimental: Lonafarnib / Paclitaxel /Carboplatin Drug: Lonafarnib
100mg/twice a day during chemotherapie,in maintenance phase 200 mg twice a day
Standard Chemotherapy
Drug: Lonafarnib
100mg/twice a day during chemotherapie,in maintenance phase 200 mg twice a day

Primary Outcome Measures :
  1. Progression-free survival [ Time Frame: every 3 months until PD ]

Secondary Outcome Measures :
  1. Objective tumor response rate (CR/PR (RECIST)) [ Time Frame: During whole trial ]
  2. Duration of response [ Time Frame: Until Progression of disease ]
  3. Overall survival [ Time Frame: Until date of death ]
  4. safety based on nature, frequency and severity of adverse events [ Time Frame: During treatment phase until resolution ]
  5. Predose lonafarnib concentrations [ Time Frame: During treatment ]
  6. PD activity [ Time Frame: Assessment ]

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00281515

Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum, Klinik für Frauenheilkunde
Berlin, Germany, 13353
Klinikum Bremen Mitte, Frauenklinik
Bremen, Germany, 28177
Carl-Gustav-Carus der TU Dresden, Universitäts-Frauenklinik
Dresden, Germany, 01307
Ev. Krankenhaus, Frauenklinik
Düsseldorf, Germany, 40217
Klinik für Frauenheilkunde der Univ. Erlangen
Erlangen, Germany, 91054
Essen, Germany, 45147
Klinikum der Johann Wolfgang Goethe Universität, Klinik für Frauenheilkunde u. Geburtshilfe
Frankfurt, Germany, 60590
Universitätsklinikum Freiburg, Frauenklinik
Freiburg, Germany, 79106
Kreiskrankenhaus, Frauenklinik
Gifhorn, Germany, 38518
Klinik u. Poliklinik für Gynäkologie und Geburtshilfe
Greifswald, Germany, 17487
Medizinische Hochschule
Hannover, Germany, 30625
St. Vincentius-Krankenhäuser
Karlsruhe, Germany, 76137
Universitätsklinikum Schleswig-Holstein, Campus Kiel, Klinik für Gynäkologie und Geburtshilfe
Kiel, Germany, 24105
Klinik der Otto-von-Guericke Universität, Frauenklinik
Magdeburg, Germany, 39108
Johannes-Gutenberg-Universität, Universitäts-Frauenklinik
Mainz, Germany, 55101
Klinikum der Philipps-Universität Marburg, Klinik für Gynäkologie, Gynäkologische Endokrinologie
Marburg, Germany, 35037
Klinikum Großhadern, Frauenklinik
München, Germany, 81377
Klinikum rechts der Isar der TU München
München, Germany, 81675
Elblandkliniken, Frauenklinik
Radebeul, Germany, 01445
Klinikum Südstadt
Rostock, Germany, 18059
Tübingen, Germany, 72076
Ulm, Germany, 89075
Dr. Horst Schmidt Klinik, Gynäkologie u. Gynäkologische Onkologie
Wiesbaden, Germany, 65199
Sponsors and Collaborators
AGO Study Group
Principal Investigator: Werner Meier, Prof. Dr. Ev. Krankenhaus, Düsseldorf, Germany

Publications of Results:
Responsible Party: AGO Study Group Identifier: NCT00281515     History of Changes
Other Study ID Numbers: AGO-OVAR 15
First Posted: January 25, 2006    Key Record Dates
Last Update Posted: June 29, 2012
Last Verified: June 2012

Additional relevant MeSH terms:
Ovarian Neoplasms
Neoplasms, Glandular and Epithelial
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Neoplasms by Histologic Type
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors