Clinical trial NCT01227928: Efficacy and Safety of Pazopanib Monotherapy After First-line Chemotherapy in Ovarian, Fallopian Tube, or Primary Peritoneal Cancer in Asian Women
Official title: A Study to Evaluate Efficacy and Safety of Pazopanib Monotherapy in Asian Women Who Have Not Progressed After First-line Chemotherapy for Advanced Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma - An Extension Study to VEG110655
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neoplasms, Ovarian
Keywords: tyrosine kinase inhibitors
Primary Peritoneal Carcinoma
primary peritoneal cancer
ovarian cancer
Fallopian Tube Cancer
gynecologic cancer
anti-angiogenesis
pazopanib
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2010-10-25
Enrollment: 145
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a study to determine whether therapy with pazopanib is effective and safe in Asian women with epithelial ovarian, fallopian tube or primary peritoneal cancer whose cancer has not progressed on first-line chemotherapy.

Detailed description: This study is an extension study to the VEG110655 study. The parent study, VEG110655, was designed to evaluate whether pazopanib 800 mg daily for 52 weeks will prolong progression free survival (PFS) in women diagnosed with ovarian, fallopian tube or primary peritoneal cancer. These women will have obtained stable disease, a complete remission, or a partial remission after debulking surgery and at least five cycles of chemotherapy (taxane/platinum). This extension study will evaluate safety and efficacy outcomes of pazopanib monotherapy and placebo in an Asian population with the same indication as the parent study.

Eligibility criteria: Inclusion Criteria:

* written informed consent
* At least 18 years old.
* Histologically confirmed, International Federation of Gynecology and Obstetrics (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
* Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to 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
* 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.
* Prior or concurrent invasive malignancies that currently or within the last 5 years show/ed activity of disease (except ovarian, fallopian tube, or peritoneal cancer, or concurrent endometrial cancer FIGO stages IA/B)

Primary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: From randomization until evidence of progressive disease or death, whichever occurred first (average of 15.2 months)
Secondary outcomes:
measure: Overall Survival
timeFrame: From randomization until death due to any cause (average of 29.4 months)
measure: PFS by Gynaecologic Cancer Intergroup (GCIG) Criteria
timeFrame: From randomization to the earliest date of disease progression per GCIG criteria or death due to any cause (average of 15.2 months)
measure: Number of Participants With Any Dose Reduction or Any Dose Interruption
timeFrame: From Week 1 until the end of the treatment period (up to Study Week 108)
measure: Number of Participants With Any Non-serious Adverse Event (AE) and Any Serious Adverse Event (SAE)
timeFrame: From Week 1 until the end of the treatment period (up to Study Week 108)
measure: Number of Participants With Any On-therapy AE and Any AE Related to Study Treatment
timeFrame: From Week 1 until the end of the treatment period (up to Study Week 108)
measure: Number of Participants With Any Grade 3 or 4 AE
timeFrame: From Week 1 until the end of the treatment period (up to Study Week 108)
measure: Number of Participants With the Indicated On-therapy Grade 3-5 AEs
timeFrame: From Week 1 until the end of the treatment period (up to Study Week 108)
measure: Number of Participants With AEs Leading to Permanent Discontinuation of Study Treatment, Dose Interruption, and Dose Reduction
timeFrame: From Week 1 until the end of the treatment period (up to Study Week 108)
measure: Number of Participants With Any SAE, Any SAE Related to Study Treatment, and Any Fatal SAE
timeFrame: From Week 1 until the end of the treatment period (up to Study Week 108)
measure: Number of Participants With the Indicated Worst-case On-therapy Blood Pressure Shifts From Baseline
timeFrame: From Week 1 until the end of the treatment period (up to Study Week 108)
measure: Number of Participants With the Indicated Worst-case On-therapy Shift From Baseline in Bazett's Corrected QT Interval (QTc)
timeFrame: From Week 1 until the end of the treatment period (up to Study Week 108)
measure: Number of Participants With the Indicated Worst-case On-therapy Hematology Parameter Grade Shifts From Baseline Grade
timeFrame: From Week 1 until the end of the treatment period (up to Study Week 108)
measure: Number of Participants With the Indicated Worst-case On-therapy Chemistry Parameter Grade Shifts From Baseline Grade
timeFrame: From Week 1 until the end of the treatment period (up to Study Week 108)
measure: Number of Participants With the Indicated Worst-case Eastern Cooperative Oncology Group (ECOG) Performance Status Shifts From Baseline Grades of 0, 1, and 2
timeFrame: From Week 1 until the end of the treatment period (up to Study Week 108)
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: GSK Investigational Site
state: Guangdong
city: Nanjing
country: China
facility: GSK Investigational Site
state: Jiangsu
city: Shenyang
country: China
facility: GSK Investigational Site
state: Liaoning
city: Jinan
country: China
facility: GSK Investigational Site
state: Shandong
city: Chengdu
country: China
facility: GSK Investigational Site
state: Sichuan
city: Hangzhou
country: China
facility: GSK Investigational Site
state: Zhejiang
city: Hangzhou
country: China
facility: GSK Investigational Site
state: Zhejiang
city: Beijing
country: China
facility: GSK Investigational Site
city: Beijing
country: China
facility: GSK Investigational Site
city: Beijing
country: China
facility: GSK Investigational Site
city: Shanghai
country: China
facility: GSK Investigational Site
city: Hong Kong
country: Hong Kong
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Taipei
country: Taiwan
facility: GSK Investigational Site
city: Taipei
country: Taiwan
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.