Pazopanib and Weekly Topotecan in Patients Recurrent Ovarian Cancer (TOPAZ)

JSehouli

Status and phase

Unknown

Phase 2

Phase 1

Conditions

Ovarian Cancer

Treatments

Drug: pazopanib in combination with weekly topotecan

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT01600573

PazTo_2010

Details and patient eligibility

About

This clinical trial shall clarify the efficacy and safety of pazopanib in combination with weekly topotecan in patients with platinum-resistant or intermediate platinum-sensitive recurrent epithelial ovarian cancer, fallopian and peritoneal carcinoma

Full description

This study is a prospective single-arm, open-label, multicenter phase I/II trial. The phase I-trial is a dose-escalation trial to determine the maximum tolerated dose (MTD) of pazopanib in combination with weekly topotecan. The phase II-trial is a single arm open-label trial to further assess the safety and the efficacy of this combination of treatment.

Enrollment

68 estimated patients

Sex

Female

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

written informed consent
histologically confirmed diagnosis of epithelial ovarian cancer, primary peritoneal carcinoma or fallopian tube cancer
platinum resistant (recurrence within 6 months of a platinum-containing regimen) or platinum refractory (progression during platinum treatment) or intermediate platinum-sensitive (recurrence within 12 months after a platinum-based primary therapy) disease
no more than 2 prior treatment regimens for epithelial ovarian cancer
Age more than 18 years
ECOG of 0 or 1
adequate organ function
measurable disease or evaluable disease according to RECIST criteria
able to swallow and retain oral medication
life expectancy of at least 12 weeks
non-childbearing potential or negative serum pregnancy test of women of childbearing potential and agrees to use adequate contraception for 14 days before exposure to investigational product, through the dosing period, and for at least 6 months after the last dose of investigational product. Female subjects who are lactating should discontinue nursing prior to the first dose of study drug and should refrain from nursing throughout the treatment period and for 14 days following the last dose of study drug.

Exclusion criteria

prior malignancies; subject who have had another malignancy and have been disease-free for 5 years which effect progression free survival, or subject with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible
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. Screening with CNS imaging studies (computed tomography [CT] or magnetic resonance imaging [MRI]) is required only if clinically indicated or if the subject has a history of CNS metastases.
clinically significant gastrointestinal abnormalities that might interfere with oral dosing or that may increase the risk for gastrointestinal bleeding
clinically significant gastrointestinal abnormalities that may affect absorption of investigational product
Grade 3 or 4 diarrhoea
Any unstable or serious concurrent condition (e.g., active infection requiring systemic therapy)
poorly controlled hypertension [defined as systolic blood pressure (SBP) of ≥140 mmHg or diastolic blood pressure (DBP) of ≥ 90mmHg]
Prolongation of corrected QT interval (QTc) >450 milliseconds using Bazett's formula
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 III or IV congestive heart failure as defined by the New York Heart Association (NYHA)
History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months
Macroscopic hematuria
Hemoptysis in excess of 2.5 mL (or one half teaspoon) within 8 weeks of first dose of study drug
Evidence of active bleeding or bleeding diathesis
known endobronchial lesions and/or lesions infiltrating major pulmonary vessels and/or involvement of large pulmonary vessels by tumor
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
Chemotherapy or radiation therapy or tumour embolization within 2 weeks prior to the first dose of study drug
biological therapy, immunotherapy, hormonal therapy or treatment with an investigational agent within 14 days (for bevacizumab, 60 days) or 5 half-lives, whichever is longer prior to the first dose of study drug
is unable or unwilling to discontinue predefined prohibited medications listed in the protocol (refer to section 4.2.3) for 14 days or five half-lives of a drug (whichever is longer) prior to first dose of study drug and for the duration of the study
any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is progressing in severity, except alopecia
known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib
psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol
clinically assessed as having inadequate venous access for PK sampling
any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study
legal incapacity or limited legal capacity
Participation in another clinical study with experimental therapy within the 30 days before start of treatment
Subjects housed in an institution on official or legal orders
Pregnancy or lactation period