Efficacy and Safety of Pazopanib Monotherapy After First Line Chemotherapy in Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Novartis

Status and phase

Completed

Phase 3

Conditions

Ovarian Cancer

Treatments

Drug: Placebo

Drug: Pazopanib

Study type

Interventional

Funder types

Industry

Identifiers

NCT00866697

2008-004672-50 (EudraCT Number)

CPZP034C2301 (Other Identifier)

110655

Details and patient eligibility

About

This was a study to determine whether therapy with pazopanib was effective and safe in women with epithelial ovarian, fallopian tube, or primary peritoneal cancer whose cancer had not progressed on first line chemotherapy.

Full description

This was a randomized, two-arm, placebo controlled, double-blind, multicenter, intergroup Phase III study in women with non-bulky FIGO (International Federation of Gynecology and Obstetrics) Stage II - IV ovarian, fallopian tube, or primary peritoneal cancer that had not progressed (i.e., complete response (CR), partial response (PR), stable disease (SD) after completing their first-line chemotherapy for advanced ovarian cancer. Approximately 900 subjects were to be enrolled into the study. Study was closed following 3rd overall survival (OS) interim analysis as planned per protocol, which confirmed futility.

Enrollment

940 patients

Sex

Female

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

written informed consent
At least 18 years old.
Histologically confirmed, FIGO stage II-IV epithelial ovarian, fallopian tube or primary peritoneal carcinoma that was treated with surgical debulking and at least five cycles of platinum-taxane doublet chemotherapy.
Study randomization at least 3 weeks and not more than 12 weeks from the date of the last chemotherapy dose, and all major toxicities from the previous chemotherapy must have resolved.
No evidence of disease progression
ECOG status of 0 or 2
Able to swallow and retain oral medication.
Adequate hematologic, hepatic, and renal system function as follows:

Hematologic

Absolute neutrophil count (ANC) at least 1.5 X 10^9/L
Hemoglobin at least 9 g/dL (or 5.59 mmol/L)
Platelets at least 100 X 10^9/L
Prothrombin time (PT) or international normalized ratio (INR) up to 1.2 X ULN
Activated partial thromboplastin time (aPTT) up to 1.2 X ULN Hepatic
Total bilirubin up to 1.5 X ULN
AST and ALT up to 2.5 X ULN Renal
Serum creatinine up to 1.5 mg/dL

Or, if greater than 1.5 mg/dL:

Calculated creatinine clearance at least 50 mL/min Urine Protein

Urine protein is 0, trace, or +1 determined by dipstick urinalysis, or < 1.0 gram determined by 24- hour urine protein analysis.
Non-childbearing potential (i.e., physiologically incapable of becoming pregnant) OR childbearing potential, and agrees to use adequate contraception.

Exclusion criteria

Either (a) bulky disease, or (b) any residual disease which in the opinion of the investigator will need imminent second-line therapy
Synchronous primary endometrial carcinoma, or a past history of primary endometrial carcinoma, are excluded unless certain conditions are met.
Clinically significant gastrointestinal abnormalities
Prolongation of corrected QT interval (QTc) > 480 msecs
History of any one or more cardiovascular conditions within the past 6 months prior to randomization
Cardiac angioplasty or stenting
Myocardial infarction
Unstable angina
Symptomatic peripheral vascular disease
- Class III or IV congestive heart failure
Poorly controlled hypertension
History of cerebrovascular accident (including transient ischemic attacks), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months prior to randomization
Major surgery (including interval debulking) or trauma within 28 days, or minor surgical procedures within 7 days, prior to randomization, or has any non-healing wound, fracture, or ulcer.
Evidence of active bleeding or bleeding diathesis.
Hemoptysis within 6 weeks prior to randomization.
Endobronchial metastases.
Serious and/or unstable pre-existing medical (e.g., uncontrolled infection), psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures.
Investigational or anti-VEGF anticancer therapy prior to study randomization.
Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib
Invasive malignancies that showed activity of disease within 5 years prior to randomization