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

NCT ID: NCT00866697

Last Updated: 2021-02-16

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

940 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-05-26

Study Completion Date

2017-08-24

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Ovarian Cancer

Study Design

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Allocation Method

RANDOMIZED

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Placebo

matched placebo tablet administered orally once daily for up to 24 months

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Matching placebo 800 mg tablet daily, for 104 weeks (24 months).

Pazopanib

Pazopanib tablet administered orally at 800 mg once daily for up to 24 months

Group Type EXPERIMENTAL

Pazopanib

Intervention Type DRUG

Pazopanib 800 mg tablet daily for 104 weeks (24 months)

Interventions

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Pazopanib

Pazopanib 800 mg tablet daily for 104 weeks (24 months)

Intervention Type DRUG

Placebo

Matching placebo 800 mg tablet daily, for 104 weeks (24 months).

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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GlaxoSmithKline

INDUSTRY

Sponsor Role collaborator

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Anaheim, California, United States

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Baldwin Park, California, United States

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Bellflower, California, United States

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Duarte, California, United States

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Fontana, California, United States

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Hayward, California, United States

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Irvine, California, United States

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Long Beach, California, United States

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Los Angeles, California, United States

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Los Angeles, California, United States

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Los Angeles, California, United States

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Oakland, California, United States

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Ontario, California, United States

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Orange, California, United States

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Panorama City, California, United States

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Riverside, California, United States

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Roseville, California, United States

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Sacramento, California, United States

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Sacramento, California, United States

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San Diego, California, United States

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San Diego, California, United States

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San Francisco, California, United States

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San Jose, California, United States

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Santa Clara, California, United States

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South San Francisco, California, United States

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Vallejo, California, United States

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Walnut Creek, California, United States

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Woodland Hills, California, United States

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Augusta, Georgia, United States

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Morristown, New Jersey, United States

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New York, New York, United States

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New York, New York, United States

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The Bronx, New York, United States

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Houston, Texas, United States

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Annandale, Virginia, United States

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Camperdown, New South Wales, Australia

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Liverpool, New South Wales, Australia

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Randwick, New South Wales, Australia

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Waratah, New South Wales, Australia

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Herston, Queensland, Australia

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South Brisbane, Queensland, Australia

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Adelaide, South Australia, Australia

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Hobart, Tasmania, Australia

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Malvern, Victoria, Australia

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Parkville, Victoria, Australia

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Wodonga, Victoria, Australia

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Nedlands, Western Australia, Australia

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Melbourne, , Australia

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Graz, , Austria

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Graz, , Austria

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Innsbruck, , Austria

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Klagenfurt, , Austria

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Korneuburg, , Austria

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Krems, , Austria

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Leoben, , Austria

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Linz, , Austria

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Linz, , Austria

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Oberpullendorf, , Austria

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Vienna, , Austria

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Vienna, , Austria

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Vienna, , Austria

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Bonheiden, , Belgium

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Duffel, , Belgium

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Ghent, , Belgium

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Kortrijk, , Belgium

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Leuven, , Belgium

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Liège, , Belgium

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Ostend, , Belgium

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Guangzhou, Guangdong, China

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Nanjing, Jiangsu, China

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Shenyang, Liaoning, China

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Jinan, Shandong, China

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Hangzhou, Zhejiang, China

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Beijing, , China

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Shanghai, , China

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Shanghai, , China

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Tianjin, , China

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Aalborg, , Denmark

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Herlev, , Denmark

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Herning, , Denmark

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Koebenhavn Oe, , Denmark

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Angers, , France

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Avignon, , France

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Besançon, , France

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Saint-Herblain, , France

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Saint-Priest-en-Jarez, , France

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Strasbourg, , France

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Suresnes, , France

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Thonon-les-Bains, , France

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Vandœuvre-lès-Nancy, , France

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Esslingen am Neckar, Baden-Wurttemberg, Germany

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Freiburg im Breisgau, Baden-Wurttemberg, Germany

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Freiburg im Breisgau, Baden-Wurttemberg, Germany

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Karlsruhe, Baden-Wurttemberg, Germany

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Karlsruhe, Baden-Wurttemberg, Germany

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Mannheim, Baden-Wurttemberg, Germany

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Mutlangen, Baden-Wurttemberg, Germany

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Reutlingen, Baden-Wurttemberg, Germany

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Schwäbisch Hall, Baden-Wurttemberg, Germany

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Tübingen, Baden-Wurttemberg, Germany

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Ulm, Baden-Wurttemberg, Germany

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Bayreuth, Bavaria, Germany

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Coburg, Bavaria, Germany

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Deggendorf, Bavaria, Germany

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Ebersberg, Bavaria, Germany

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Eggenfelden, Bavaria, Germany

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Fürth, Bavaria, Germany

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Munich, Bavaria, Germany

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Munich, Bavaria, Germany

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Munich, Bavaria, Germany

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Schweinfurt, Bavaria, Germany

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Darmstadt, Hesse, Germany

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Frankfurt am Main, Hesse, Germany

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Frankfurt am Main, Hesse, Germany

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Fulda, Hesse, Germany

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Kassel, Hesse, Germany

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Lich, Hesse, Germany

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Limburg an der Lahn, Hesse, Germany

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Marburg, Hesse, Germany

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Offenbach, Hesse, Germany

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Offenbach, Hesse, Germany

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Wiesbaden, Hesse, Germany

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Wiesbaden, Hesse, Germany

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Braunschweig, Lower Saxony, Germany

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Cuxhaven, Lower Saxony, Germany

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Georgsmarienhütte, Lower Saxony, Germany

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Gifhorn, Lower Saxony, Germany

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Goslar, Lower Saxony, Germany

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Göttingen, Lower Saxony, Germany

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Hanover, Lower Saxony, Germany

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Hanover, Lower Saxony, Germany

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Hanover, Lower Saxony, Germany

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Hildesheim, Lower Saxony, Germany

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Leer, Lower Saxony, Germany

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Lüneburg, Lower Saxony, Germany

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Oldenburg, Lower Saxony, Germany

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Salzgitter, Lower Saxony, Germany

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Wolfsburg, Lower Saxony, Germany

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Greifswald, Mecklenburg-Vorpommern, Germany

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Rostock, Mecklenburg-Vorpommern, Germany

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Bonn, North Rhine-Westphalia, Germany

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Bonn, North Rhine-Westphalia, Germany

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Bonn, North Rhine-Westphalia, Germany

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Bonn, North Rhine-Westphalia, Germany

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Cologne, North Rhine-Westphalia, Germany

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Detmold, North Rhine-Westphalia, Germany

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Dortmund, North Rhine-Westphalia, Germany

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Düsseldorf, North Rhine-Westphalia, Germany

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Essen, North Rhine-Westphalia, Germany

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Essen, North Rhine-Westphalia, Germany

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Essen, North Rhine-Westphalia, Germany

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Neuss, North Rhine-Westphalia, Germany

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Troisdorf, North Rhine-Westphalia, Germany

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Viersen, North Rhine-Westphalia, Germany

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Mainz, Rhineland-Palatinate, Germany

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Trier, Rhineland-Palatinate, Germany

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Chemnitz, Saxony, Germany

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Dresden, Saxony, Germany

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Radebeul, Saxony, Germany

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Zwickau, Saxony, Germany

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Halle, Saxony-Anhalt, Germany

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Magdeburg, Saxony-Anhalt, Germany

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Magdeburg, Saxony-Anhalt, Germany

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Salzwedel, Saxony-Anhalt, Germany

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Flensburg, Schleswig-Holstein, Germany

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Kiel, Schleswig-Holstein, Germany

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Lübeck, Schleswig-Holstein, Germany

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Gera, Thuringia, Germany

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Nordhausen, Thuringia, Germany

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Berlin, , Germany

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Berlin, , Germany

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Hamburg, , Germany

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Hamburg, , Germany

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Hamburg, , Germany

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Hong Kong, , Hong Kong

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Kowloon, , Hong Kong

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Dublin, , Ireland

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Dublin, , Ireland

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Waterford, , Ireland

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Wilton, Cork, , Ireland

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Bari, Apulia, Italy

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Potenza, Basilicate, Italy

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Avellino, Campania, Italy

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Napoli, Campania, Italy

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Bologna, Emilia-Romagna, Italy

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Bologna, Emilia-Romagna, Italy

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Carpi (MO), Emilia-Romagna, Italy

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Faenza (RA), Emilia-Romagna, Italy

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Reggio Emilia, Emilia-Romagna, Italy

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Aviano (PN), Friuli Venezia Giulia, Italy

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Rome, Lazio, Italy

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Rome, Lazio, Italy

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Como, Lombardy, Italy

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Milan, Lombardy, Italy

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Milan, Lombardy, Italy

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Milan, Lombardy, Italy

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Milan, Lombardy, Italy

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Milan, Lombardy, Italy

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Monza, Lombardy, Italy

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Sondrio, Lombardy, Italy

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Varese, Lombardy, Italy

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Campobasso, Molise, Italy

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Turin, Piedmont, Italy

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Turin, Piedmont, Italy

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Palermo, Sicily, Italy

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Perugia, Umbria, Italy

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Vicenza, Veneto, Italy

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Ehime, , Japan

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Fukuoka, , Japan

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Hiroshima, , Japan

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Hiroshima, , Japan

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Hokkaido, , Japan

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Kagoshima, , Japan

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Miyagi, , Japan

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Numakunai, , Japan

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Osaka, , Japan

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Saitama, , Japan

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Tokyo, , Japan

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Tokyo, , Japan

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Tokyo, , Japan

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Tokyo, , Japan

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Tottori, , Japan

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Bergen, , Norway

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Oslo, , Norway

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Stavanger, , Norway

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Tromsø, , Norway

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Goyang-si, Gyeonggi-do, , South Korea

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Kangnam-Ku ,Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Alcorcon (Madrid), , Spain

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Barcelona, , Spain

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Barcelona, , Spain

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Novartis Investigative Site

Barcelona, , Spain

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Novartis Investigative Site

Barcelona, , Spain

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Novartis Investigative Site

Cartagena (Murcia), , Spain

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Donostia / San Sebastian, , Spain

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Elche, , Spain

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Lleida, , Spain

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Madrid, , Spain

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Novartis Investigative Site

Madrid, , Spain

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Novartis Investigative Site

Madrid, , Spain

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Novartis Investigative Site

Madrid, , Spain

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Novartis Investigative Site

Madrid, , Spain

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Novartis Investigative Site

Murcia (El Palmar), , Spain

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Palma de Mallorca, , Spain

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Pamplona, , Spain

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Sabadell (Barcelona), , Spain

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Novartis Investigative Site

Santiago de Compostela, , Spain

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Novartis Investigative Site

Terrassa, , Spain

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Novartis Investigative Site

Valencia, , Spain

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Novartis Investigative Site

Valencia, , Spain

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Novartis Investigative Site

Zaragoza, , Spain

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Novartis Investigative Site

Linköping, , Sweden

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Novartis Investigative Site

Lund, , Sweden

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Novartis Investigative Site

Stockholm, , Sweden

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Novartis Investigative Site

Uppsala, , Sweden

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Novartis Investigative Site

Taipei, , Taiwan

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Novartis Investigative Site

Taipei, , Taiwan

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Countries

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United States Australia Austria Belgium China Denmark France Germany Hong Kong Ireland Italy Japan Norway South Korea Spain Sweden Taiwan

References

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Gaitskell K, Rogozinska E, Platt S, Chen Y, Abd El Aziz M, Tattersall A, Morrison J. Angiogenesis inhibitors for the treatment of epithelial ovarian cancer. Cochrane Database Syst Rev. 2023 Apr 18;4(4):CD007930. doi: 10.1002/14651858.CD007930.pub3.

Reference Type DERIVED
PMID: 37185961 (View on PubMed)

Vergote I, du Bois A, Floquet A, Rau J, Kim JW, Del Campo JM, Friedlander M, Pignata S, Fujiwara K, Colombo N, Mirza MR, Monk BJ, Tsibulak I, Calvert PM, Herzog TJ, Hanker LC, Meunier J, Lee JY, Bologna A, Carrasco-Alfonso MJ, Harter P. Overall survival results of AGO-OVAR16: A phase 3 study of maintenance pazopanib versus placebo in women who have not progressed after first-line chemotherapy for advanced ovarian cancer. Gynecol Oncol. 2019 Nov;155(2):186-191. doi: 10.1016/j.ygyno.2019.08.024. Epub 2019 Sep 10.

Reference Type DERIVED
PMID: 31519320 (View on PubMed)

Friedlander M, Rau J, Lee CK, Meier W, Lesoin A, Kim JW, Poveda A, Buck M, Scambia G, Shimada M, Hilpert F, King MT, Debruyne P, Bologna A, Malander S, Monk BJ, Petru E, Calvert P, Herzog TJ, Barrett C, du Bois A. Quality of life in patients with advanced epithelial ovarian cancer (EOC) randomized to maintenance pazopanib or placebo after first-line chemotherapy in the AGO-OVAR 16 trial. Measuring what matters-patient-centered end points in trials of maintenance therapy. Ann Oncol. 2018 Mar 1;29(3):737-743. doi: 10.1093/annonc/mdx796.

Reference Type DERIVED
PMID: 29267856 (View on PubMed)

Pulford DJ, Harter P, Floquet A, Barrett C, Suh DH, Friedlander M, Arranz JA, Hasegawa K, Tada H, Vuylsteke P, Mirza MR, Donadello N, Scambia G, Johnson T, Cox C, Chan JK, Imhof M, Herzog TJ, Calvert P, Wimberger P, Berton-Rigaud D, Lim MC, Elser G, Xu CF, du Bois A. Communicating BRCA research results to patients enrolled in international clinical trials: lessons learnt from the AGO-OVAR 16 study. BMC Med Ethics. 2016 Oct 21;17(1):63. doi: 10.1186/s12910-016-0144-y.

Reference Type DERIVED
PMID: 27769273 (View on PubMed)

Kim JW, Mahner S, Wu LY, Shoji T, Kim BG, Zhu JQ, Takano T, Park SY, Kong BH, Wu Q, Wang KL, Ngan HY, Liu JH, Wei LH, Mitrica I, Zhang P, Crescenzo R, Wang Q, Cox CJ, Harter P, du Bois A. Pazopanib Maintenance Therapy in East Asian Women With Advanced Epithelial Ovarian Cancer: Results From AGO-OVAR16 and an East Asian Study. Int J Gynecol Cancer. 2018 Jan;28(1):2-10. doi: 10.1097/IGC.0000000000000602.

Reference Type DERIVED
PMID: 26588236 (View on PubMed)

Floquet A, Vergote I, Colombo N, Fiane B, Monk BJ, Reinthaller A, Calvert P, Herzog TJ, Meier W, Kim JW, del Campo JM, Friedlander M, Pisano C, Isonishi S, Crescenzo RJ, Barrett C, Wang K, Mitrica I, du Bois A. Progression-free survival by local investigator versus independent central review: comparative analysis of the AGO-OVAR16 Trial. Gynecol Oncol. 2015 Jan;136(1):37-42. doi: 10.1016/j.ygyno.2014.11.074. Epub 2014 Nov 28.

Reference Type DERIVED
PMID: 25434635 (View on PubMed)

du Bois A, Floquet A, Kim JW, Rau J, del Campo JM, Friedlander M, Pignata S, Fujiwara K, Vergote I, Colombo N, Mirza MR, Monk BJ, Kimmig R, Ray-Coquard I, Zang R, Diaz-Padilla I, Baumann KH, Mouret-Reynier MA, Kim JH, Kurzeder C, Lesoin A, Vasey P, Marth C, Canzler U, Scambia G, Shimada M, Calvert P, Pujade-Lauraine E, Kim BG, Herzog TJ, Mitrica I, Schade-Brittinger C, Wang Q, Crescenzo R, Harter P. Incorporation of pazopanib in maintenance therapy of ovarian cancer. J Clin Oncol. 2014 Oct 20;32(30):3374-82. doi: 10.1200/JCO.2014.55.7348. Epub 2014 Sep 15.

Reference Type DERIVED
PMID: 25225436 (View on PubMed)

Provided Documents

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Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2008-004672-50

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CPZP034C2301

Identifier Type: OTHER

Identifier Source: secondary_id

110655

Identifier Type: -

Identifier Source: org_study_id

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