A Study to Evaluate Pazopanib in Comparison to Pemetrexed in Maintenance Setting in Non-progressing Subjects With Metastatic Stage IVA and IVB Non-squamous Non-small Cell Lung Cancer (NSCLC) Population

NCT01313663 | Terminated Phase 2 Results

• 1 other identifier: 113758
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 25

Brief Summary

This is a Phase II, randomized, open-label, multi-center study in advanced (Stage IVA and IVB subjects per the International Association for the Study of Lung Cancer (IASLC) 2009 Lung cancer staging schema) non-squamous NSCLC subjects comparing pazopanib relative to pemetrexed in the maintenance setting. Subjects should have completed 4-6 cycles of induction therapy with carboplatin + pemetrexed or cisplatin + pemetrexed and have had Stable Disease (SD), Partial Response (PR) or Complete Response (CR) as the best response to be enrolled into the study. The primary objective is to estimate the hazard ratio of progression free survival (PFS) in advanced NSCLC subjects given maintenance therapy of pazopanib (Arm A) relative to pemetrexed (Arm B). The secondary objectives are: overall survival, response rates, safety and tolerability. A total of approximately 200 subjects will be enrolled and randomized in a 1:1 ratio. Safety and efficacy assessments will be regularly performed on all subjects.

Conditions

Lung Cancer, Small Cell

Keywords

GW786034; non-small cell lung cancer; NSCLC; pemetrexed; pazopanib

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  PFS is defined as the interval between the date of randomization and the first documented sign of investigator-assessed (per Response Evaluation Criteria in Solid Tumors \[RECIST\] version 1.1) disease progression (PD) or death, whichever occurs first. The date of documented PD is the date of lesion evaluation in the case of radiological PD and the date of symptomatic cancer progression in the case of symptomatic progression (radiological confirmation is required). PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started. If the participant received subsequent anti-cancer therapy prior to the date of documented progression or death, PFS was to be censored at the last adequate assessment (LAA) prior to the initiation of therapy. Otherwise, if the participant did not have a documented date of progression or death, PFS was to be censored at the date of the LAA.

  From randomization until the first documented sign of investigator-assessed disease progression or death, whichever occurred first (average of 10 study weeks)

Secondary Outcomes (14)

• Overall Survival

  From randomization until disease progression or death (up to Study Week 78)

• Number of Participants (Par.) With the Indicated Best Overall Response

  From randomization until the time of the first documented evidence of a confirmed complete response (CR) or partial response (PR) (average of 10 weeks)

• Number of Participants With Any Non-serious On-therapy Adverse Event (AE: Occurring in >=5% Participants in Any Treatment Arm) and Serious Adverse Event (SAE)

  From the time the first dose of study treatment was administered until 28 days following discontinuation of study treatment regardless of initiation of a new cancer therapy or transfer to hospice (up to Study Week 55)

• Time on Study Treatment (Pazopanib), as a Measure of Extent of Exposure

  From the first day to the last day of treatment (average of 8 weeks)

• Mean Daily Dose, as a Measure of Extent of Exposure

  From the first day to the last day of treatment (average of 8 weeks)

Study Arms (2)

Pazopanib

EXPERIMENTAL

oral agent, administered at 800 mg daily (400 mg tablets x 2). Dose can be reduced, interrupted or discontinued due to adverse events or intolerance

Drug: pazopanib

Pemetrexed

ACTIVE COMPARATOR

pemetrexed IV 500 mg/m2 once every 3 weeks

Drug: pemetrexed

Interventions

pazopanib DRUG

oral agent, administered at 800 mg daily (400 mg tablets x 2). Dose can be reduced, interrupted or discontinued due to adverse events or intolerance

Pazopanib

pemetrexed DRUG

pemetrexed IV 500 mg/m2 once every 3 weeks

Pemetrexed

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written Informed Consent.
• Subjects must complete 4 to 6 cycles of chemotherapy with carboplatin + pemetrexed or cisplatin + pemetrexed and have had SD, PR or CR at the time of screening/enrolment as the best response.
• Prior surgery and/or localized irradiation for NSCLC is permitted as long as it was a minimum of 4 weeks before entering the study. Subjects with recurrence after previous NSCLC that has been treated with surgery and adjuvant chemotherapy or a radio-chemotherapy regimen with curative intent are eligible, provided 1 year has passed since this treatment ended.
• Histologically or cytologically confirmed diagnosis of predominantly non-squamous cell Stage IVA Wet (with cytology positive Malignant Pleural Effusion (MPE)) or Stage IVB (metastatic) NSCLC.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Life expectancy of at least 12 weeks.
• Must have measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST). A measurable lesion is defined as a lesion that can be accurately measured in at least one dimension with the longest diameter ≥ 20 mm using conventional techniques, or ≥ 10 mm with spiral computed tomography (CT) scan.
• Able to swallow and retain oral medication.
• Adequate organ system function.
• Women of childbearing potential must have a negative pregnancy test within \<= 7 days prior to administration or dispensing of study treatment and agree to use effective contraception.
• Age ≥ 18 years of legal age of consent if different from 18 years.

You may not qualify if:

• History of active or any other malignancy other than lung cancer in the 2 yrs prior to the first dose of study drug other than NSCLC. Exception: Subjects 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 medications for 4 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 may increase the risk for gastrointestinal bleeding including, but not limited to:
• Active peptic ulcer disease
• Known intraluminal metastatic lesion/s with risk of bleeding
• Inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), or other gastrointestinal conditions with increased risk of perforation
• History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment
• Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to:
• Malabsorption syndrome Major resection of the stomach or small bowel
• Presence of uncontrolled infection.
• Corrected QT interval (QTc) \> 480 msecs 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 Coronary artery bypass graft surgery Symptomatic peripheral vascular disease Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA).
• \- Poorly controlled hypertension, defined as systolic blood pressure (SBP) of ≥140 mmHg or diastolic blood pressure (DBP) of
• mmHg.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (25)

GSK Investigational Site

Tucson, Arizona, 85704, United States

Location

GSK Investigational Site

Skokie, Illinois, 60076, United States

Location

GSK Investigational Site

Skokie, Illinois, 60077, United States

Location

GSK Investigational Site

Indianapolis, Indiana, 46219, United States

Location

GSK Investigational Site

Ames, Iowa, 50010, United States

Location

GSK Investigational Site

Overland Park, Kansas, 66210, United States

Location

GSK Investigational Site

Pikeville, Kentucky, 41501, United States

Location

GSK Investigational Site

Columbia, Missouri, 65201, United States

Location

GSK Investigational Site

Las Vegas, Nevada, 89128, United States

Location

GSK Investigational Site

Latham, New York, 12110, United States

Location

GSK Investigational Site

Raleigh, North Carolina, 27607, United States

Location

GSK Investigational Site

Fargo, North Dakota, 58103, United States

Location

GSK Investigational Site

Charleston, South Carolina, 29425, United States

Location

GSK Investigational Site

Chattanooga, Tennessee, 37421, United States

Location

GSK Investigational Site

Bedford, Texas, 76022, United States

Location

GSK Investigational Site

Dallas, Texas, 75230, United States

Location

GSK Investigational Site

Dallas, Texas, 75231, United States

Location

GSK Investigational Site

Dallas, Texas, 75246, United States

Location

GSK Investigational Site

Garland, Texas, 75042, United States

Location

GSK Investigational Site

Houston, Texas, 77090, United States

Location

GSK Investigational Site

Mesquite, Texas, 75150, United States

Location

GSK Investigational Site

San Marcos, Texas, 78666, United States

Location

GSK Investigational Site

Tyler, Texas, 75702, United States

Location

GSK Investigational Site

Everett, Washington, 98201, United States

Location

GSK Investigational Site

Vancouver, Washington, 98684, United States

Location

MeSH Terms

Conditions

Small Cell Lung Carcinoma; Carcinoma, Non-Small-Cell Lung

Interventions

pazopanib; Pemetrexed

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 27, 2011
• First Posted: March 14, 2011
• Study Start: February 1, 2011
• Primary Completion: July 1, 2012
• Study Completion: July 1, 2012
• Last Updated: October 27, 2014
• Results First Posted: April 29, 2013

Record last verified: 2013-10

Locations

US (25)