Clinical trial NCT00492206: Study of Cetuximab With Radiation Followed by Consolidation Chemotherapy for NSCLC
Official title: A Phase II Study of Cetuximab in Combination With External Beam Radiation Followed By Consolidation Chemotherapy for Patients With Locally Advanced Non-Small Cell Lung Cancer (NSCLC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non Small Cell Lung Cancer (NSCLC)
Keywords: Non Small Cell Lung Cancer
NSCLC
EGFR Inhibitor
Radiation Therapy
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
First posted: 2007-06-27
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an open label, phase II study in which cetuximab with concurrent thoracic radiotherapy followed by consolidation chemotherapy with paclitaxel/carboplatin/cetuximab will be administered to subjects with locally advanced NSCLC.

Detailed description: This is a Phase II study to determine the overall survival for patients with locally advanced NSCLC treated with cetuximab with concurrent thoracic radiotherapy followed by consolidation chemotherapy with paclitaxel/carboplatin/cetuximab. This is a multicenter study including 36 subjects who will be males and females, both greater than 18 years of age. All subjects will initially receive radiation and cetuximab. Radiation will be given once a day (Monday-Friday) for approximately 6-8 weeks. During the course of radiation, cetuximab will be given intravenously once a week. Approximately 4-6 weeks after the last radiation dose, the subjects will be treated with chemotherapy, paclitaxel/carboplatin. Chemotherapy will be given intravenously once every 3 weeks for 3 cycles (1 cycle=3 weeks). Cetuximab intravenous administration will be continued throughout the entire study, once a week through week 26 including during chemotherapy.

Eligibility criteria: Inclusion Criteria:

* Patients must have histologically or cytologically confirmed diagnosis of non-small cell lung cancer
* Patients must have surgically unresectable stage IIIA disease or stage IIIB disease without malignant pleural/pericardial effusion
* Patients must have measurable disease as per the RECIST criteria, defined as 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 CT scan. See section 9.2 for the evaluation of measurable disease.
* Age \>18 years. Lung cancer is extremely rare in children.
* ECOG performance status 0-1 (Karnofsky \>70%; see Appendix A).
* If available, tumor tissue should be submitted for EGFR status by IHC and correlative studies.
* Patients must have normal organ and marrow function as defined below:
* leukocytes \>3,000/μL
* absolute neutrophil count \>1,500/μL
* platelets \>100,000/μL
* total bilirubin within normal institutional limits
* AST(SGOT)/ALT(SGPT) \<2.5 X institutional upper limit of normal
* creatinine within normal institutional limits OR
* creatinine clearance \>60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
* The effects of cetuximab on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because EGFR inhibitors, chemotherapeutic agents and radiation therapy, as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
* Patients must either be not of child bearing potential or have a negative pregnancy test within 7 days of treatment. Patients are considered not of child bearing potential if they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal.
* Willingness to sign an approved informed consent.

Exclusion Criteria:

* Patients should not have received prior chest radiation therapy.
* Patients with a history of pulmonary fibrosis are excluded from study.
* Patients may not be receiving any other investigational agents.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to carboplatin, paclitaxel, cetuximab or other agents used in the study.
* History of any cancer other than NSCLC (except non-melanoma skin cancer or carcinoma in situ of the cervix) within the last five years.
* Prior therapy with known specific inhibitors of the EGFR.
* History of severe allergic reaction to prior therapy with monoclonal antibodies
* Peripheral neuropathy of more than grade 1 in severity
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, significant history of uncontrolled cardiac disease ie. uncontrolled hypertension, unstable angina, recent myocardial infarction (within prior 6 months), uncontrolled congestive heart failure,and cardiomyopathy with decreased ejection fraction, or psychiatric illness/social situations that would limit compliance with study requirements.
* Pregnant women are excluded from this study because carboplatin, paclitaxel, cetuximab and radiation therapy have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with the above agents, breastfeeding should be discontinued if the mother is treated with the agents used in this study. These potential risks may also apply to other agents used in this study.
* Patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy. Therefore, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with carboplatin, paclitaxel and cetuximab or other agents administered during the study. Appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated.
* Active hepatitis.
* History of pulmonary fibrosis.

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to 36 months
Secondary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: Up to 36 months
measure: Best Overall Response Rate (ORR) (Number of Participants)
timeFrame: Up to 12 weeks after treatment initiation
measure: EGFR (Epidermal Growth Factor Receptor) Gene Mutation and Akt, pAkt, and MAPKinase
timeFrame: approx. 5 years
Other outcomes:
Locations:
city: Miami
country: United States
facility: Sylvester Comprehensive Cancer Center, University of Miami
state: Florida
city: Atlanta
country: United States
facility: Emory Winship Cancer Institute
state: Georgia
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at John Hopkins
state: Maryland
city: Steubenville
country: United States
facility: UPMC Cancer Center -Teramana Cancer Center
state: Ohio
city: Beaver
country: United States
facility: UPMC Cancer Center -Beaver
state: Pennsylvania
city: Clairton
country: United States
facility: UPMC Cancer Center - Clairton
state: Pennsylvania
city: Greensburg
country: United States
facility: UPMC Cancer Center - Oakbrook Commons
state: Pennsylvania
city: Greensburg
country: United States
facility: UPMC Cancer Center -Arnold Palmer Pavilion
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Cancer Institute, Penn State Milton S. Hershey Medical Center
state: Pennsylvania
city: Indiana
country: United States
facility: UPMC Cancer Center -Indiana
state: Pennsylvania
city: Johnstown
country: United States
facility: UPMC Cancer Center -John P. Murtha Pavilion
state: Pennsylvania
city: McKeesport
country: United States
facility: UPMC Cancer Center -McKeesport
state: Pennsylvania
city: Monroeville
country: United States
facility: UPMC Cancer Center -Haymaker Rd.
state: Pennsylvania
city: Monroeville
country: United States
facility: UPMC Cancer Center -Mosside Blvd.
state: Pennsylvania
city: Moon Township
country: United States
facility: UPMC Cancer Center -Sewickley Medical Center
state: Pennsylvania
city: Mt. Pleasant
country: United States
facility: UPMC Cancer Center -Mt. Pleasant
state: Pennsylvania
city: New Castle
country: United States
facility: UPMC Cancer Center -Jameson
state: Pennsylvania
city: New Castle
country: United States
facility: UPMC Cancer Center -New Castle
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Presbyterian -Radiation Oncology
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Cancer Center -Delafield Rd.
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Cancer Center -St. Margaret
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Universtity of Pittsburgh Cancer Institute -Hillman Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Cancer Center -UPMC Shadyside
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Cancer Center -Passavant
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Cancer Center -Drake
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Cancer Center -St. Clair
state: Pennsylvania
city: Seneca
country: United States
facility: UPMC Cancer Center -UPMC Northwest
state: Pennsylvania
city: Uniontown
country: United States
facility: UPMC Cancer Center -Robert Eberly Pavilion
state: Pennsylvania
city: Uniontown
country: United States
facility: UPMC Cancer Center -Uniontown
state: Pennsylvania
city: Washington
country: United States
facility: UPMC Cancer Center -Washington
state: Pennsylvania
city: Wexford
country: United States
facility: UPMC Cancer Center -Wexford
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Athanassios Argiris, MD
role: PRINCIPAL_INVESTIGATOR
References: