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

Epithelial Ovarian Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00281515
• Other study ID #: AGO-OVAR 15
• Status: Completed
• Phase: Phase 2
• First received: January 24, 2006
• Last updated: June 28, 2012
• Start date: January 2006
• Est. completion date: December 2011

Study information

• Verified date: June 2012
• Source: AGO Study Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 105
• Est. completion date: December 2011
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Epithelial Ovarian Cancer
• Neoplasms, Glandular and Epithelial
• Ovarian Neoplasms

Intervention

Drug:
• Lonafarnib
100mg/twice a day during chemotherapie,in maintenance phase 200 mg twice a day

Locations

Country	Name	City	State
Germany	Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum, Klinik für Frauenheilkunde	Berlin
Germany	Klinikum Bremen Mitte, Frauenklinik	Bremen
Germany	Carl-Gustav-Carus der TU Dresden, Universitäts-Frauenklinik	Dresden
Germany	Ev. Krankenhaus, Frauenklinik	Düsseldorf
Germany	Klinik für Frauenheilkunde der Univ. Erlangen	Erlangen
Germany	Universitätsfrauenklinik	Essen
Germany	Klinikum der Johann Wolfgang Goethe Universität, Klinik für Frauenheilkunde u. Geburtshilfe	Frankfurt
Germany	Universitätsklinikum Freiburg, Frauenklinik	Freiburg
Germany	Kreiskrankenhaus, Frauenklinik	Gifhorn
Germany	Klinik u. Poliklinik für Gynäkologie und Geburtshilfe	Greifswald
Germany	Medizinische Hochschule	Hannover
Germany	St. Vincentius-Krankenhäuser	Karlsruhe
Germany	Universitätsklinikum Schleswig-Holstein, Campus Kiel, Klinik für Gynäkologie und Geburtshilfe	Kiel
Germany	Klinik der Otto-von-Guericke Universität, Frauenklinik	Magdeburg
Germany	Johannes-Gutenberg-Universität, Universitäts-Frauenklinik	Mainz
Germany	Klinikum der Philipps-Universität Marburg, Klinik für Gynäkologie, Gynäkologische Endokrinologie	Marburg
Germany	Klinikum Großhadern, Frauenklinik	München
Germany	Klinikum rechts der Isar der TU München	München
Germany	Elblandkliniken, Frauenklinik	Radebeul
Germany	Klinikum Südstadt	Rostock
Germany	Universitäts-Frauenklinik	Tübingen
Germany	Universitätsfrauenklinik	Ulm
Germany	Dr. Horst Schmidt Klinik, Gynäkologie u. Gynäkologische Onkologie	Wiesbaden

Sponsors (1)

Lead Sponsor	Collaborator
AGO Study Group

Country where clinical trial is conducted

Germany, 

References & Publications (1)

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 wit — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival		every 3 months until PD	No
Secondary	Objective tumor response rate (CR/PR (RECIST))		During whole trial	No
Secondary	Duration of response		Until Progression of disease	No
Secondary	Overall survival		Until date of death	No
Secondary	safety based on nature, frequency and severity of adverse events		During treatment phase until resolution	Yes
Secondary	Predose lonafarnib concentrations		During treatment	No
Secondary	PD activity		Assessment	No