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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Priv.-Doz. Dr. med. Joachim Rom, University Hospital Heidelberg
ClinicalTrials.gov Identifier:
NCT01238770
First received: November 10, 2010
Last updated: July 21, 2015
Last verified: July 2015
  Purpose

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.


Condition Intervention Phase
Epithelial Ovarian Cancer
Drug: Pazopanib
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Pazopanib (GW786034) and Cyclophosphamide in Patients With Platinum-resistant Recurrent, Pre-treated Ovarian Cancer

Resource links provided by NLM:


Further study details as provided by University Hospital Heidelberg:

Primary Outcome Measures:
  • Determination of the optimal doses for pazopanib (phase I) [ Time Frame: 42 months ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to progression (TTP) according to RECIST criteria [ Time Frame: 7 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 7 years ] [ Designated as safety issue: Yes ]
  • Evaluation of CA125 tumour response [ Time Frame: 7 years ] [ Designated as safety issue: No ]
  • Number of patients with Adverse Events [ Time Frame: 7 years ] [ Designated as safety issue: Yes ]
  • Assessment of quality of life over time as defined by EORTC-QLQ C 30 and Ovar 28 questionnaire [ Time Frame: 7 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 57
Study Start Date: November 2010
Estimated Study Completion Date: August 2015
Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cyclophosphamid + Pazopanib
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 Name: Cyclophosphamid

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT01238770

Locations
Germany
Marienkrankenhaus Hamburg
Hamburg, Germany, 22087
Universitäts-Frauenklinik
Heidelberg, Germany, 69120
Klinikum Konstanz Gynäkologie und Geburtshilfe
Konstanz, Germany, 78464
Universitätsmedizin der Johannes Gutenberg-Universität Mainz Klinik und Poliklinik für Geburtshilfe und Frauenheilkunde
Mainz, Germany, 55131
Universitätsfrauenklinik Tübingen Klinik für Gynäkologie und Geburtshilfe
Tübingen, Germany, 72076
Sponsors and Collaborators
Priv.-Doz. Dr. med. Joachim Rom
Investigators
Principal Investigator: Michael Eichbaum, PD Dr. med. Medizinische Fakultät Heidelberg Abteilung für Frauenheilkunde und Geburtshilfe
  More Information

No publications provided by University Hospital Heidelberg

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Priv.-Doz. Dr. med. Joachim Rom, PD Dr. med, University Hospital Heidelberg
ClinicalTrials.gov Identifier: NCT01238770     History of Changes
Other Study ID Numbers: 3107000
Study First Received: November 10, 2010
Last Updated: July 21, 2015
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by University Hospital Heidelberg:
Ovarian cancer

Additional relevant MeSH terms:
Neoplasms, Glandular and Epithelial
Ovarian Neoplasms
Adnexal Diseases
Endocrine Gland Neoplasms
Endocrine System Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Gonadal Disorders
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Ovarian Diseases
Urogenital Neoplasms
Cyclophosphamide
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on July 30, 2015