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

Phase 1

Completed

Brief Summary: 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.

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

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Investigational Treatment	Pemetrexed	Pemetrexed + cetuximab for patients with recurrent non-small cell lung cancer.
Investigational Treatment	Cetuximab	Pemetrexed + cetuximab for patients with recurrent non-small cell lung cancer.

Primary Outcome Measures

Name	Time	Method
Maximum Tolerated Dose (MTD) of Pemetrexed in Combination With Cetuximab	12 months	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
Time To Progression (TTP)	24 Months	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

Secondary Outcome Measures

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

Locations (11): Medical & Surgical Specialists, LLC
🇺🇸
Galesburg, Illinois, United States
Greenebaum Cancer Center
🇺🇸
Baltimore, Maryland, United States
Northern Indiana Cancer Research Consortium
🇺🇸
South Bend, Indiana, United States
Texas Oncology Cancer Center
🇺🇸
Austin, Texas, United States
Medical Consultants, P.C.
🇺🇸
Muncie, Indiana, United States
Center for Cancer Care at Goshen Health System
🇺🇸
Goshen, Indiana, United States
Fort Wayne Oncology & Hematology, Inc
🇺🇸
Fort Wayne, Indiana, United States
Indiana University Cancer Center
🇺🇸
Indianapolis, Indiana, United States
Elkhart Clinic
🇺🇸
Elkhart, Indiana, United States
Cancer Care Center of Southern Indiana
🇺🇸
Bloomington, Indiana, United States
Oncology Hematology Care, Inc.
🇺🇸
Cincinnati, Ohio, United States