Pemetrexed Plus Cetuximab in Patients With Recurrent Non Small Cell Lung Cancer

A Phase I-IIa Dose-Ranging Study of Pemetrexed (Alimta) Plus Cetuximab (Erbitux) in Patients With Recurrent Non-Small Cell Lung Cancer (NSCLC): Hoosier Oncology Group LUN04-79

Both pemetrexed and cetuximab have single agent activity in NSCLC and non-overlapping toxicity profiles. While 2-drug combination therapy has proven superior to single agent therapy in the first-line setting of NSCLC, no such phase III trials have been reported in the second-line setting. Therefore, the purpose of this study is to determine the feasibility of combining these drugs, assessing the toxicity profile, determining the MTD and evaluating the activity of the combination in an expanded phase II setting. If the combination appears to have promising activity, further evaluation of this regimen may be warranted comparing it to single agent pemetrexed or cetuximab alone.

Study Overview

• Status: Completed
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Pemetrexed; Drug: Cetuximab

Detailed Description

OUTLINE: This is a multi-center study.

Week 1 (day 1):

• Cetuximab 400mg/m2

Week 2 (Cycle 1, Day 1):

• Cetuximab 250mg/m2 plus premetrexed at the assigned dose level.

Patients will be treated with cetuximab on day 1, 8, 15 of each 21 day cycle.

Patients will be treated with pemetrexed on day 1 of each 21 day cycle for a maximum of 6 cycles.

Acceptable toxicity and SD, PR or CR: treat up to 6 cycles then continue cetuximab weekly until PD or excess toxicity

Performance status: ECOG 0-2

Life expectancy: At least 12 weeks

Hematopoietic:

• ANC > 1,500/mm3
• Platelets > 100,000/mm3

Hepatic:

• Bilirubin less than or equal to the upper limit of normal (ULN)
• Aspartate aminotransferase (AST) < 1.5 X ULN. AST may be < 5 X ULN for patients with liver metastases
• Alkaline phosphatase < 5 X ULN

Renal:

• Calculated creatinine clearance > 45 mL/min (by Cockcroft-Gault)

Cardiovascular:

• No significant history of uncontrolled cardiac disease (i.e., uncontrolled hypertension, unstable angina, and congestive heart failure)

Pulmonary:

• Not specified

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Galesburg, Illinois, United States, 61401
      • Medical & Surgical Specialists, LLC
  • Indiana
    • Bloomington, Indiana, United States, 47403
      • Cancer Care Center of Southern Indiana
    • Elkhart, Indiana, United States, 46515
      • Elkhart Clinic
    • Fort Wayne, Indiana, United States, 46815
      • Fort Wayne Oncology & Hematology, Inc
    • Goshen, Indiana, United States, 46527
      • Center for Cancer Care at Goshen Health System
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Cancer Center
    • Muncie, Indiana, United States, 47303
      • Medical Consultants, P.C.
    • South Bend, Indiana, United States, 46601
      • Northern Indiana Cancer Research Consortium
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Greenebaum Cancer Center
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Oncology Hematology Care, Inc.
  • Texas
    • Austin, Texas, United States, 78731
      • Texas Oncology Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologic or cytologic diagnosis of NSCLC
• Recurrent or metastatic disease that is not amenable to curative therapyMeasurable disease according to RECIST
• At least one prior platinum containing regimen for either locally advanced or metastatic disease
• Prior chemotherapy must be completed at least 21 days prior to being registered for protocol therapy and the subject must have recovered from the acute toxicity effects of the regimen
• Ability and willingness to interrupt aspirin or other nonsteroidal anti-inflammatory agents for a 5-day period
• Prior radiation therapy allowed to < 25% of the bone marrow
• Negative pregnancy test

Exclusion Criteria:

• No active infection that in the opinion of the investigator would compromise the subject's ability to tolerate therapy.
• No serious concomitant systemic disorders that would compromise the safety of the subject or compromise the subject's ability to complete the study, at the discretion of the investigator.
• No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the subject has been disease-free for at least 2 years.
• No major thoracic or abdominal surgery within 30 days prior to being registered for protocol therapy.
• No current breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Investigational Treatment; Pemetrexed + cetuximab for patients with recurrent non-small cell lung cancer.	Drug: Pemetrexed; Pemetrexed at the assigned dose, day 1 of each 21 day cycle for a maximum of 6 cycles; Drug: Cetuximab; Cetuximab 400 mg/m2, week 1, day 1 Cetuximab 250 mg/m2, day 1, 8, 15 of each 21 day cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Tolerated Dose (MTD) of Pemetrexed in Combination With Cetuximab	The primary objective of the phase I portion of this study is to define the maximum tolerated dose (MTD) of the combination of pemetrexed and cetuximab	12 months
Time To Progression (TTP)	The primary objective of the phase II portion is to estimate the time to progression of this combination, evaluated per RECIST criteria where PD= at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions	24 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Survival Time		24 Months
Toxicity and Safety Profile		12 months
Clinical Benefit Rate	Clinical Benefit Rate (CR + PR + SD lasting more than 90 days)	12 months

Collaborators and Investigators

• Sponsor: Nasser Hanna, M.D.
• Collaborators: Bristol-Myers Squibb; Eli Lilly and Company; Walther Cancer Institute
• Investigators: Study Chair: Nasser Hanna, M.D., Hoosier Oncology Group, LLC

Publications and helpful links

General Publications

• Jalal S, Waterhouse D, Edelman MJ, Nattam S, Ansari R, Koneru K, Clark R, Richards A, Wu J, Yu M, Bottema B, White A, Hanna N. Pemetrexed plus cetuximab in patients with recurrent non-small cell lung cancer (NSCLC): a phase I/II study from the Hoosier Oncology Group. J Thorac Oncol. 2009 Nov;4(11):1420-4. doi: 10.1097/JTO.0b013e3181b624ae.

Helpful Links

• Hoosier Oncology Group Home Page

Study record dates

Study Major Dates

• Study Start: May 1, 2005
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: September 12, 2005
• First Submitted That Met QC Criteria: September 14, 2005
• First Posted (Estimate): September 22, 2005

Study Record Updates

• Last Update Posted (Estimate): September 29, 2016
• Last Update Submitted That Met QC Criteria: August 22, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: Non-Small Cell Lung Cancer
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Folic Acid Antagonists; Pemetrexed; Cetuximab
• Other Study ID Numbers: HOG LUN04-79

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO