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

Launched by PRIV.-DOZ. DR. MED. JOACHIM ROM · Nov 10, 2010

Keywords

ClinConnect Summary

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.

Gender

FEMALE

Eligibility 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