Pharmacodynamic Separation of Pemetrexed and Erlotinib as Second-line Therapy in Patients With Advanced Non-small Cell Lung Cancer (NSCLC)

Official Title: “A Randomized Phase II Study of Schedule-Modulated Concomitant Pemetrexed and Erlotinib Versus Single Agent Pemetrexed in Patients With Progressive or Recurrent Non-Small Cell Lung Cancer (NSCLC)”

RATIONALE: Erlotinib may stop the growth of tumor cells, and even shrink the tumors in some patients, by blocking some of the enzymes such as epidermal growth factor receptor (EGFR) needed for cell growth and spread. Pemetrexed is a drug that inhibits several key proteins that require folic acid to synthesize DNA. Blocking DNA synthesis in tumor cells has been shown to decrease tumor growth. can block tumor growth in different ways. Giving erlotinib together with pemetrexed at a specific schedule may kill more tumor cells than giving only pemetrexed.

PURPOSE: This phase I/II trial is studying the side effects and best dose of erlotinib and cetuximab and to see how well they work in treating patients with advanced solid tumors or progressive or recurrent stage III or stage IV non-small cell lung cancer.

Intervention(s) in this Clinical Trial

• Drug: Pemetrexed
  • 500 mg/m2 IV over 10 minutes on day 1 every 21 days
• Drug: pemetrexed and erlotinib
  • pemetrexed 500 mg/m2 IV over 10 minutes on day 1 every 21 days and erlotinib 150 mg PO once daily on days 2-17 every 21 days

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: A
  • Pemetrexed Monotherapy
• Experimental: B
  • Pharmacodynamic separation of pemetrexed and erlotinib

Primary Measures

• Progression-free survival
  • Time Frame: 6 months
    Safety Issue?: No

Secondary Measures

• Objective response rate
  • Time Frame: Every 6 weeks while on study
    Safety Issue?: No
• Disease control rate
  • Time Frame: 6 months
    Safety Issue?: No
• Safety profile of pemetrexed and erlotinib combination
  • Time Frame: Continously
    Safety Issue?: Yes
• Assessment of molecular markers for biologic effects and predictive response
  • Time Frame: while on study
    Safety Issue?: No

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed advanced (Stage IIIB with a malignant pleural effusion or Stage IV disease) or recurrent nonsquamous
• NSCLC.
• Patients must have at least one measurable disease per RECIST criteria
• Patient must have disease progression after one prior chemotherapy and/or targeted therapy other than pemetrexed or anti-EGFR therapy for metastatic disease, or relapse while receiving adjuvant therapy, or within 12 months of completing adjuvant therapy

Exclusion Criteria:

• Patients who have had immunotherapy, hormone, chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
• Patients with uncontrolled brain metastases should be excluded from this clinical trial because of their poor prognosis.
• Patients with immune deficiency

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Montefiore Medical Center Other

Overall Clinical Trial Officials and Contacts

Tianhong Li, MD, PhD Study Chair Montefiore Medical Center  

Overall Contact: Tianhong Li, MD, PhD 718-904-2900 tli@montefiore.org

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00950365

Study ID Number: Pemetrexed/Erlotinib

ClinicalTrials.gov Identifier: NCT00950365

Health Authority: United States: Institutional Review Board