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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AGO Study Group
ClinicalTrials.gov Identifier:
NCT00281515
First received: January 24, 2006
Last updated: June 28, 2012
Last verified: June 2012
  Purpose

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 Intervention Phase
Epithelial Ovarian Cancer
Drug: Lonafarnib
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by AGO Study Group:

Primary Outcome Measures:
  • Progression-free survival [ Time Frame: every 3 months until PD ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Objective tumor response rate (CR/PR (RECIST)) [ Time Frame: During whole trial ] [ Designated as safety issue: No ]
  • Duration of response [ Time Frame: Until Progression of disease ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Until date of death ] [ Designated as safety issue: No ]
  • safety based on nature, frequency and severity of adverse events [ Time Frame: During treatment phase until resolution ] [ Designated as safety issue: Yes ]
  • Predose lonafarnib concentrations [ Time Frame: During treatment ] [ Designated as safety issue: No ]
  • PD activity [ Time Frame: Assessment ] [ Designated as safety issue: No ]

Enrollment: 105
Study Start Date: January 2006
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lonafarnib / Paclitaxel /Carboplatin Drug: Lonafarnib
100mg/twice a day during chemotherapie,in maintenance phase 200 mg twice a day
Paclitaxel/Carboplatin
Standard Chemotherapy
Drug: Lonafarnib
100mg/twice a day during chemotherapie,in maintenance phase 200 mg twice a day

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00281515

Locations
Germany
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
Universitätsfrauenklinik
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
Universitäts-Frauenklinik
Tübingen, Germany, 72076
Universitätsfrauenklinik
Ulm, Germany, 89075
Dr. Horst Schmidt Klinik, Gynäkologie u. Gynäkologische Onkologie
Wiesbaden, Germany, 65199
Sponsors and Collaborators
AGO Study Group
Investigators
Principal Investigator: Werner Meier, Prof. Dr. Ev. Krankenhaus, Düsseldorf, Germany
  More Information

Publications:
Responsible Party: AGO Study Group
ClinicalTrials.gov Identifier: NCT00281515     History of Changes
Other Study ID Numbers: AGO-OVAR 15
Study First Received: January 24, 2006
Last Updated: June 28, 2012
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Ovarian Neoplasms
Neoplasms, Glandular and Epithelial
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Neoplasms by Histologic Type
Carboplatin
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014