Phase I/II Study of Pazopanib and Cyclophosphamide in Patients With Platinum-resistant Recurrent Ovarian Cancer

February 8, 2016 updated by: Priv.-Doz. Dr. med. Joachim Rom

A Phase I/II Study of Pazopanib (GW786034) and Cyclophosphamide in Patients With Platinum-resistant Recurrent, Pre-treated Ovarian Cancer

The current trial shall clarify the potential of the multitarget antiangiogenic tyrosinkinase inhibitor GW 786034 (pazopanib) in combination with oral cyclophosphamide as salvage treatment in patients with recurrent, pretreated ovarian cancer.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This study is a prospective open-label, non-randomized multicenter phase I/II trial in order to determine overall response rate of patients with platinum-resistant or refractory recurrent, pretreated epithelial ovarian cancer.

In order to assure adequate toxicity assessment, a phase-I-trial is proponed. Phase II will be performed with MTD.

Study Type

Interventional

Enrollment (Actual)

10

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Hamburg, Germany, 22087
        • Marienkrankenhaus Hamburg
      • Heidelberg, Germany, 69120
        • Universitäts-Frauenklinik
      • Konstanz, Germany, 78464
        • Klinikum Konstanz Gynäkologie und Geburtshilfe
      • Mainz, Germany, 55131
        • Universitätsmedizin der Johannes Gutenberg-Universität Mainz Klinik und Poliklinik für Geburtshilfe und Frauenheilkunde
      • Tübingen, Germany, 72076
        • Universitätsfrauenklinik Tübingen Klinik für Gynäkologie und Geburtshilfe

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  1. Written informed consent
  2. Female subjects ≥18 years of age
  3. Histologically or cytologically confirmed diagnosis of: epithelial ovarian cancer which is platinum resistant or platinum refractory,cancer of the fallopian tube, peritoneal cancer
  4. Patients must have failed available standard chemotherapy regimen
  5. Prior treatment with at least 2 chemotherapy regimens in advanced tumor setting
  6. Performance status ECOG 0 - 2
  7. Adequate contraception
  8. Adequate organ function
  9. Measurable disease according to RECIST criteria.
  10. Able to swallow and retain oral medication.
  11. Life expectancy of at least 12 weeks.

Exclusion Criteria:

  1. Any second malignancy within the last 5 years, with the exception of basal cell or squamous cell skin cancer or in situ carcinoma of the cervix uteri
  2. History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for 6 months prior to first dose of study drug.
  3. Clinically significant gastrointestinal abnormalities which might interfere with oral dosing
  4. Any unstable or serious concurrent condition (e.g., active infection requiring systemic therapy).
  5. Prolongation of corrected QT interval (QTc) >480 msecs.

  6. History of any one or more of the following cardiovascular conditions within the past 6 months:

    • Cardiac angioplasty or stenting
    • Myocardial infarction
    • Unstable angina
    • Symptomatic peripheral vascular disease
    • Coronary artery by-pass graft surgery
    • Class II, III or IV congestive heart failure as defined by the New York Heart Association (NYHA)
    • History of cerebrovascular accident, pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months
  7. Macroscopic hematuria
  8. Hemoptysis that is clinically relevant within 4 weeks of first dose of study drug
  9. Evidence of active bleeding or bleeding diathesis
  10. Known endobronchial lesions or involvement of large pulmonary vessels by tumor
  11. Prior major surgery or trauma within 14 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer.
  12. Chemotherapy or radiation therapy within 2 weeks prior to the first dose of study drug.
  13. Biological therapy, hormonal therapy or treatment with an investigational agent within 28 days or 5 half-lives
  14. Prior antiangiogenic therapy.
  15. Is unable or unwilling to discontinue predefined prohibited medications listed in the protocol for 14 days or five half-lives of a drug (whichever is longer) prior to Visit 1 and for the duration of the study
  16. Any ongoing toxicity from prior anti-cancer therapy that is > Grade 1 and/or that is progressing in severity.
  17. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib
  18. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
  19. Pregnancy
  20. More than 3 different chemotherapy regimens in advanced tumor setting
  21. Uncontrolled hypertension
  22. History of ischemic event (stroke, myocardial infarction, unstable angina, TIA, symptomatic peripheral vascular disease)
  23. History or clinical evidence of thrombo-embolic event
  24. History of haemoptysis, cerebral, or clinically significant gastrointestinal haemorrhage in the past 6 months
  25. Active bleeding
  26. Signs/Suspicion of intestinal obstruction

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cyclophosphamid + Pazopanib
Drug: Pazopanib

Phase I Cyclophosphamid Pazopanib Dose level I 50 mg/day 400 mg/day Dose level II 50 mg/day 600 mg/day Dose level III 50 mg/day 800 mg/day

Cyclophosphamide 50 mg daily orally Pazopanib 400, 600 or 800 mg daily orally

Phase II:

Cyclophosphamide 50 mg daily orally Pazopanib 400, 600 or 800 mg daily orally The dose for the phase II part of the trial will be based on the MTD of phase I.

Other Names:
  • Cyclophosphamid

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Determination of the optimal doses for pazopanib (phase I)
Time Frame: 42 months
42 months
Overall response rate according to RECIST criteria / clinical benefit (stable disease or partial response or complete response) (phase II)
Time Frame: 12 weeks after start of treatment
12 weeks after start of treatment

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall survival
Time Frame: 7 years
7 years
Time to progression (TTP) according to RECIST criteria
Time Frame: 7 years
7 years
Evaluation of CA125 tumour response
Time Frame: 7 years
7 years
Number of patients with Adverse Events
Time Frame: 7 years
7 years
Assessment of quality of life over time as defined by EORTC-QLQ C 30 and Ovar 28 questionnaire
Time Frame: 7 years
7 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Priv.-Doz. Dr. med. Joachim Rom

Investigators

  • Principal Investigator: Michael Eichbaum, PD Dr. med., Medizinische Fakultät Heidelberg Abteilung für Frauenheilkunde und Geburtshilfe

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2010

Primary Completion (Actual)

October 1, 2014

Study Completion (Actual)

October 1, 2015

Study Registration Dates

First Submitted

November 10, 2010

First Submitted That Met QC Criteria

November 10, 2010

First Posted (Estimate)

November 11, 2010

Study Record Updates

Last Update Posted (Estimate)

February 10, 2016

Last Update Submitted That Met QC Criteria

February 8, 2016

Last Verified

February 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 3107000

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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