Anti-angiogenesis Agent AG-013736 in Patients With Advanced Non-Small Cell Lung Cancer

• ClinicalTrials.gov Identifier: NCT00094094
• Recruitment Status: Completed
• First Posted: October 14, 2004
• Results First Posted: March 16, 2012
• Last Update Posted: June 26, 2012
• Sponsor: Pfizer
• Information provided by: Pfizer

Tracking Information

• First Submitted Date: October 11, 2004
• First Posted Date: October 14, 2004
• Results First Submitted Date: February 25, 2012
• Results First Posted Date: March 16, 2012
• Last Update Posted Date: June 26, 2012
• Study Start Date: February 2005
• Actual Primary Completion Date: July 2007 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 25, 2012)

Percentage of Participants With Objective Response (OR) [ Time Frame: Baseline until the date of first documented progression or discontinuation from the study due to any cause, assessed every 8 weeks up to 98 weeks ]

Percentage of participants with OR based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. CR are defined as the disappearance of all lesions (target and/or non target). PR are those with at least 30 percent (%) decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.

• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: February 25, 2012)

• Progression-Free Survival (PFS) [ Time Frame: Baseline until the date of first documented progression or death due to any cause, assessed every 8 weeks up to 98 weeks ]
  Time in days from start of study treatment to first documentation of objective tumor progression or death due to any cause. PFS was calculated as first event date minus the date of first dose of study medication plus 1. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]), or from adverse event (AE) data (where the outcome was "Death").
• Duration of Response (DR) [ Time Frame: Baseline until the date of first documented progression or discontinuation from the study due to any cause, assessed every 8 weeks up to 98 weeks ]
  Time in days from the first documentation of objective tumor response to objective tumor progression or death due to any cause. Duration of tumor response was calculated as the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1. DR was calculated for the subgroup of participants with a confirmed objective tumor response.
• Overall Survival (OS) [ Time Frame: Baseline to death due to any cause or at least 1 year after the initial dose for the last treated participant ]
  Time in days from the start of study treatment to date of death due to any cause. OS was calculated as the death date minus the date of first dose of study medication plus 1. Death was determined from AE data (where outcome was death) or from follow-up contact data (where the participant current status was death). For participants who were alive, overall survival was censored at the last contact.

• Original Secondary Outcome Measures: Not Provided

Current Other Pre-specified Outcome Measures (submitted: February 25, 2012)

• Population Pharmacokinetics for Axitinib (AG-013736) Plasma Concentrations [ Time Frame: Day 1 (pre-dose), Day 29, Day 57 and then every 8 weeks up to 98 weeks ]
  Population pharmacokinetic analysis involved mixed effects modeling using nonlinear mixed effects modeling (NONMEM) software. The intent of this analysis was to establish a basic population pharmacokinetic model for axitinib (AG-013736) and to determine inter-individual and residual variability in population (oral) clearance, and volume of distribution of drug. Relationship of demographic variables (gender, age, body weight, height and ethnicity), concomitant medications and measures of altered hepatic and renal function were examined by fitting measured axitinib (AG-013736) concentrations.
• Plasma Concentrations of Soluble Proteins [ Time Frame: Day 1 (pre-dose) and then every 8 weeks up to 98 weeks ]
  Plasma concentrations of soluble proteins (vascular endothelial growth factor [VEGF], placental growth factor [PlGF] and soluble vascular endothelial growth factor receptor-2 [sVEGFR2]) may be associated with tumor angiogenesis or tumor physiology and may correlate with efficacy or biological activity. It is presented as ratio to baseline, which is obtained by dividing the plasma soluble protein concentration at each time point by its concentration at baseline.

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Anti-angiogenesis Agent AG-013736 in Patients With Advanced Non-Small Cell Lung Cancer
• Official Title: Phase 2 Study of the Anti-Angiogenesis Agent AG-013736 as Second- or Later- Line Treatment in Patients With Advanced Non-Small Cell Lung Cancer
• Brief Summary: This is a Phase 2 study being conducted at multiple centers in the United States and Germany. Patients having non-small cell lung cancer that has spread to other parts of the body (i.e., metastatic) or is locally advanced (i.e., Stage IIIB with malignant pleural effusion) are eligible to participate. Patients must have disease that has been treated with at least 1 prior treatment for metastatic disease (prior adjuvant treatment for localized disease does not count as prior treatment for metastatic disease). The purpose of the study is to test whether the angiogenesis inhibitor AG-013736 is an effective treatment for advanced non-small cell lung cancer as shown by the number of patients in the study who experience significant and durable tumor shrinkage
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Lung Neoplasms
• Carcinoma, Non-small Cell Lung

Intervention

Drug: axitinib

Axitinib (AG-013736) tablet administered orally at a dose of 5 milligrams (mg) twice daily (BID) in cycles of 4 weeks.

Study Arms

Experimental: Axitinib

AG-013736 is a vascular endothelial growth factor [VEGF] inhibitor

Intervention: Drug: axitinib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 6, 2005): 32
• Original Enrollment: Not Provided
• Actual Study Completion Date: July 2007
• Actual Primary Completion Date: July 2007 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Histologically documented non-small cell lung cancer with metastases (Stage IV or recurrent disease) or locally advanced (Stage IIIB) with malignant pleural effusion.
• At least 1 prior systemic therapy for metastatic disease (Prior adjuvant therapy for localized disease does not count as a prior therapy for metastatic disease).

Exclusion Criteria:

• Central lung lesions involving major blood vessels (arteries or veins). (Central lesions that maintain the structural integrity of vessels have the potential to bleed if the tumor lesion undergoes necrosis. MRI or CT angiography should be used in any case where there is any question as to whether blood vessels are involved.)
• Patients with a history of Grade 2 or worse hemoptysis are not eligible. Patients with a history of Grade 1 hemoptysis within 30 days of entry are not eligible

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany, United States

Administrative Information

• NCT Number: NCT00094094
• Other Study ID Numbers: A4061011
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Not Provided
• Original Responsible Party: Same as current
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: June 2012