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

• Register: ClinicalTrials.gov
• Last refreshed on: 24 October 2016
• Main ID: NCT01600573
• Date of registration: 09/05/2012
• Prospective Registration: No
• Primary sponsor: JSehouli
• Public title: Pazopanib and Weekly Topotecan in Patients Recurrent Ovarian Cancer (TOPAZ)
• Scientific title: A Phase I/II Study of Pazopanib and Weekly Topotecan in Patients With Platinum-resistant or Intermediate-sensitive Recurrent Ovarian Cancer
• Date of first enrolment: May 2012
• Target sample size: 68
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/show/NCT01600573
• Study type: Interventional
• Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
• Phase: Phase 1/Phase 2

Countries of recruitment

Germany

Contacts

• Name: Jalid Sehouli, Prof. Dr.

• Name: jalid Sehouli, Prof. Dr.
• Affiliation: Charité Campus Virchow-Klinikum

• Name: Jalid Sehouli, Prof. Dr.

Key inclusion & exclusion criteria

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



Age minimum: 18 Years
Age maximum: N/A
Gender: Female

Health Condition(s) or Problem(s) studied

Ovarian Cancer

Intervention(s)

Drug: pazopanib in combination with weekly topotecan

Primary Outcome(s)

Phase I: Assessment of dose-limiting toxicity in order to determine the maximum tolerated dose (MTD) of pazopanib in combination with weekly topotecan [Time Frame: after 4 weeks]

• Phase II: Progression-free survival according to RECIST criteria [Time Frame: up to 3.5 years]

Secondary Outcome(s)

• Evaluation of CA-125 tumour response [Time Frame: up to 3.5 years]

• Clinical benefit rate (CR, PR, SD) [Time Frame: up to 3.5 years]

• Overall survival [Time Frame: up to 3.5 years]

• Duration of response [Time Frame: up to 3.5 years]

• Quality of life as defined by EORTC-QLQ C 30 and Ovar 28 questionnaire [Time Frame: up to 3.5 years]

• Time to progression (TTP) [Time Frame: up to 3.5 years]

Safety and tolerability of pazopanib in combination with weekly topotecan [Time Frame: up to 3.5 years]

• Response rate (CR, PR) according to RECIST criteria [Time Frame: up to 3.5 years]

Secondary ID(s)

PazTo_2010

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

GlaxoSmithKline