Study of Pazopanib and Pemetrexed in Advanced Non-small C... | NCT00871403

NCT00871403

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Label	Type	Description	Intervention Names
Arm 1	Experimental	Investigational treatment (pazopanib and pemetrexed)	Drug: pazopanib and pemetrexed
Arm 2	Active Comparator	Standard treatment (pemetrexed and cisplatin)	Drug: pemetrexed and cisplatin

Name	Type	Description	Arm Group Labels	Other Names
pazopanib and pemetrexed	Drug	oral pazopanib 600 mg once daily and pemetrexed intravenous (IV) 500mg/m^2 once every 3 weeks, then pazopanib 800 mg once daily	Arm 1

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Progression-free Survival (PFS)	PFS is defined as the interval between the date of randomization (date on which the investigator evaluated the participant and first determined he/she had disease progression) and the first occurrence of progressive disease (PD) or death from any cause. Per Response Evaluation Criteria in Solid Tumors (RECIST), version 1, PD is defined as a >=20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of >=1 new lesion).	Randomization until progression or death (up to 85 weeks)

Secondary Outcomes

Measure	Description	Time Frame
Overall Survival (OS)	OS was determined from the date of randomization to the date of death from any cause. Participants who had not died at the time of the cut-off for the final analysis were censored at the date the participants were last known to be alive. Because enrollment in the study was halted prematurely, the ability to achieve an estimate of OS was compromised. Consequently, OS was not estimated.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Written informed consent
At least 18 years old
Histologically- or cytologically-confirmed diagnosis of predominantly nonsquamous cell Stage IIIBwet (with confirmed malignant pleural effusion) or Stage IV NSCLC
No prior systemic first-line therapy for advanced NSCLC
Measurable disease
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Life expectancy of at least 12 weeks
Able to swallow and retain oral medication
Adequate organ system function (hematological, hepatic, and renal)
Non-childbearing potential (i.e., physiologically incapable of becoming pregnant) OR childbearing potential, and agrees to use adequate contraception. A male with a female partner of childbearing potential is eligible if he uses a barrier method of contraception or abstinence during the study

Exclusion Criteria:

Active malignancy or any malignancy in the 3 years prior to first dose of study drug other than NSCLC
Central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for asymptomatic, previously treated CNS metastases
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
Major surgery or trauma within 28 days or any non-healing wound, fracture, or ulcer
Evidence of active bleeding or bleeding diathesis
Recent hemoptysis
Endobronchial lesions and/or lesions infiltrating major pulmonary vessels
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
Use of any prohibited medication
Use of an investigational agent within 28 days or 5 half-lives, whichever is longer, prior to the first dose of study drug
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, pemetrexed, and/or cisplatin
Inability to interrupt aspirin or other non-steroidal anti-inflammatory drugs during the study
Inability or unwillingness to take folic acid, vitamin B12 supplementation, or dexamethasone
Clinically significant third-space fluid collections (e.g., ascites or pleural effusions) that cannot be controlled by drainage or other procedures prior to study start
Recent or concurrent yellow fever vaccination

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Herlev		2730	Denmark
GSK Investigational Site

Arm/Group Information

ID	Title	Description
FG000	Pazopanib 600 mg Plus Pemetrexed 500 mg/m^2	Oral pazopanib 600 milligrams (mg) once daily plus intravenous pemetrexed 500 mg/meters squared (m^2) once every 3 weeks for 4 or 6 cycles during the Combination Treatment Phase.
FG001	Pazopanib 800 mg Plus Pemetrexed 500 mg/m^2	Oral pazopanib 800 mg once daily plus intravenous (IV) pemetrexed 500 mg/ m^2 once every 3 weeks for 4 or 6 cycles during the Combination Treatment Phase. If participants experienced no disease progression, unacceptable toxicities, or death during the Combination Treatment Phase, they continued on pazopanib 800 mg monotherapy until disease progression, unacceptable toxicities, or death.
FG002	Cisplatin 75 mg/m^2 Plus Pemetrexed 500 mg/m^2	IV cisplatin 75 mg/m^2 plus intravenous pemetrexed 500 mg/m^2 once daily every 3 weeks for 4 or 6 cycles during the Combination Treatment Phase. Until Protocol Amendment 2, upon disease progression participants had the opportunity to receive pazopanib 800 mg monotherapy if the investigator considered it an appropriate treatment option after considering alternative options for second-line treatment.

Periods

Title

Milestones

Reasons Not Completed

Combination Treatment Phase

Type	Comment	Milestone Data
STARTED		FG0009 subjects FG00162 subjects FG00235 subjects
COMPLETED		FG0000 subjectsNo particiapants completed Combination Treatement. FG00113 subjectsThese participants completed combination treatment FG00223 subjectsThese participants completed combination treatment
NOT COMPLETED		FG0009 subjects FG00149 subjects FG00212 subjects

Type	Comment	Reasons
Randomized but Not Treated		FG0001 subjects FG0011 subjects FG0021 subjects
Treatment Stopped; Protocol Amendment		FG000

Monotherapy Treatment Phase

Type	Comment	Milestone Data
STARTED		FG0000 subjects FG00113 subjects FG0021 subjects
COMPLETED		FG000

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Pazopanib 600 mg Plus Pemetrexed 500 mg/m^2	Oral pazopanib 600 milligrams (mg) once daily plus intravenous pemetrexed 500 mg/meters squared (m^2) once every 3 weeks for 4 or 6 cycles during the Combination Treatment Phase.
BG001	Pazopanib 800 mg Plus Pemetrexed 500 mg/m^2

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Progression-free Survival (PFS)

PFS is defined as the interval between the date of randomization (date on which the investigator evaluated the participant and first determined he/she had disease progression) and the first occurrence of progressive disease (PD) or death from any cause. Per Response Evaluation Criteria in Solid Tumors (RECIST), version 1, PD is defined as a >=20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of >=1 new lesion).

Intent-to-Treat (ITT) Population: all participants randomized to receive treatment and who were analyzed based on the assigned randomized treatment and not based on actual treatment received/not received. Participants who had neither progressed nor died were censored at the date of the last adequate tumor assessment at the time of the cut-off.

Posted

Median

95% Confidence Interval

weeks

Randomization until progression or death (up to 85 weeks)

ID	Title	Description
OG000

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Pazopanib 600 mg Plus Pemetrexed 500 mg/m^2	Oral pazopanib 600 milligrams (mg) once daily plus intravenous pemetrexed 500 mg/meters squared (m^2) once every 3 weeks for 4 or 6 cycles during the Combination Treatment Phase.

ID	Term
D002283	Carcinoma, Bronchogenic
D001984	Bronchial Neoplasms
D008175	Lung Neoplasms
D012142	Respiratory Tract Neoplasms

ID	Term
D006147	Guanine
D007042	Hypoxanthines
D011688	Purinones
D011687	Purines
D006574