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

This study has been completed.
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: February 8, 2016
Last verified: February 2016

November 10, 2010
February 8, 2016
November 2010
October 2014   (final data collection date for primary outcome measure)
  • 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 ]
  • Determination of the optimal doses for pazopanib (phase I) [ Time Frame: Phase I during treatment ] [ 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 ]
Complete list of historical versions of study NCT01238770 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Time to progression (TTP) according to RECIST criteria [ Time Frame: Treatment and FU period ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Treatment and FU period ] [ Designated as safety issue: Yes ]
  • Evaluation of CA125 tumour response [ Time Frame: Treatment and FU period ] [ Designated as safety issue: No ]
  • Safety and tolerability [ Time Frame: Treatment and FU period ] [ 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: Treatment and FU period ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Phase I/II Study of Pazopanib and Cyclophosphamide in Patients With Platinum-resistant Recurrent Ovarian Cancer
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.

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.

Interventional
Phase 1
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Epithelial Ovarian Cancer
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
Experimental: Cyclophosphamid + Pazopanib
Cyclophosphamid + Pazopanib
Intervention: Drug: Pazopanib
Eichbaum M, Mayer C, Eickhoff R, Bischofs E, Gebauer G, Fehm T, Lenz F, Fricke HC, Solomayer E, Fersis N, Schmidt M, Wallwiener M, Schneeweiss A, Sohn C. The PACOVAR-trial: a phase I/II study of pazopanib (GW786034) and cyclophosphamide in patients with platinum-resistant recurrent, pre-treated ovarian cancer. BMC Cancer. 2011 Oct 20;11:453. doi: 10.1186/1471-2407-11-453.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
10
October 2015
October 2014   (final data collection date for primary outcome measure)

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
Female
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Germany
 
NCT01238770
3107000
Yes
Not Provided
Not Provided
Priv.-Doz. Dr. med. Joachim Rom, University Hospital Heidelberg
Priv.-Doz. Dr. med. Joachim Rom
Not Provided
Principal Investigator: Michael Eichbaum, PD Dr. med. Medizinische Fakultät Heidelberg Abteilung für Frauenheilkunde und Geburtshilfe
University Hospital Heidelberg
February 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP