A Randomized Phase II Double-Blind Trial of Erlotinib and Pazopanib, or Erlotinib and Placebo in Patients With Previously Treated Advanced Non-Small-Cell Lung Cancer (NSCLC)
Overview
- Phase
- Phase 2
- Intervention
- Pazopanib
- Conditions
- Non Small Cell Lung Cancer
- Sponsor
- SCRI Development Innovations, LLC
- Enrollment
- 202
- Locations
- 8
- Primary Endpoint
- Progression-free Survival
- Status
- Completed
- Last Updated
- 10 years ago
Overview
Brief Summary
This randomized, placebo-controlled, Phase II trial will compare the combination of erlotinib with pazopanib (providing concurrent EGFR and VEGFR inhibition) with erlotinib alone in the second- or third-line treatment of patients with advanced NSCLC. This study will be conducted though the Sarah Cannon Research Consortium, a community-based clinical trial network.
Detailed Description
Erlotinib is the current treatment standard for second- or third-line therapy of advanced NSCLC. Since angiogenesis inhibitors have also shown activity in NSCLC, the simultaneous inhibition of the EGFR and VEGF pathway may improve the efficacy of therapy. In a recently reported Phase III trial (Hainsworth et al. 2008), the combination of bevacizumab and erlotinib improved the Progression- Free-Survival (PFS) vs. erlotinib alone when given as second-line therapy in NSCLC (3.4 months vs. 1.7 months, respectively; HR 0.63). Pazopanib also inhibits the angiogenesis pathway, and may have advantages over bevacizumab including: (1) inhibition of other potentially important targets, including PDGFR; and (2) more convenient oral administration.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Pathologic confirmation of stage IIIB/IV NSCLC (squamous carcinoma, adenocarcinoma, or large cell carcinoma) per the American Joint Committee on Cancer Cancer Staging Manual, 6th edition. Patients with mixed tumors with small- cell elements are ineligible.
- •At least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>20 mm with conventional techniques, or as \>10 mm with spiral computerized tomography scan according to the Response Evaluation Criteria in Solid Tumors version 1.1 (Eisenhauer et al. 2009)
- •Failure of at least 1, and no more than 2, prior chemotherapy regimens for advanced disease (either due to progressive disease or toxicity).
- •Recovery from any toxic effects of prior therapy to ≤ grade 1 per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE).
- •Completion of radiation therapy at least 28 days prior to the start of study treatment (not including palliative local radiation). Previously irradiated lesions in the advanced setting cannot be included as target lesions unless clear tumor progression has been observed since the end of radiation.
- •ECOG Performance Status of 0-
- •Adequate hematologic, hepatic and renal function.
- •A female is eligible to enter and participate in this study if she is of:
- •non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who has had hysterectomy, bilateral oophorectomy (ovariectomy), bilateral tubal ligation, is post-menopausal
- •childbearing potential, including any female who has had a negative serum pregnancy test within 1 week prior to the first dose of study treatment, preferably as close to the first dose as possible, and agrees to use adequate contraception.
Exclusion Criteria
- •Past or current history of neoplasm (other than the entry diagnosis), with the exception of treated non-melanoma skin cancer or carcinoma in-situ of the cervix, or other cancers cured by local therapy alone, and a disease-free survival ≥3 years.
- •Prior treatment with EGFR tyrosine kinase inhibitors or vascular endothelial factor receptor tyrosine kinase inhibitors for NSCLC. \[Note: prior bevacizumab (Avastin®) use is permitted\].
- •Prior use of an investigational agent within 28 days or 5 half-lives, whichever is longer, prior to the first dose of study drug.
- •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 New York Heart Association classification
Arms & Interventions
Erlotinib + Pazopanib
Erlotinib: 150 mg orally daily Pazopanib: 600 mg orally daily
Intervention: Pazopanib
Erlotinib + Pazopanib
Erlotinib: 150 mg orally daily Pazopanib: 600 mg orally daily
Intervention: Erlotinib
Erlotinib + Placebo
Erlotinib: 150 mg orally daily Placebo: orally daily
Intervention: Erlotinib
Outcomes
Primary Outcomes
Progression-free Survival
Time Frame: 14 months
The length of time, in months, that patients were alive from first date of protocol treatment until worsening of disease. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Secondary Outcomes
- Overall Survival(18 months)
- Objective Response Rate (ORR)(18 Months)