Cetuximab Plus Conformal Thoracic Radiotherapy in Patients (Pts) With Inoperable or Unresectable Locally Advanced Non-Small Cell Lung Cancer (LA - NSCLC)

Study Overview
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Brief Summary
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This research is being done to find out if a treatment consisting of a combination of thoracic radiotherapy with cetuximab, given together, and followed by chemotherapy with docetaxel and cetuximab (also given together) will kill the cancer cells in the patient's body and shrink the size of their tumor without causing unacceptable side effects. This may allow patients to live longer or decrease the frequency and/or severity of the symptoms caused by the cancer without increasing the frequency and/or severity of the symptoms caused by the treatment.

Detailed Description
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Patients will be asked to spend about six months in this study. There will be 4 different phases in this study as follows: (1) Loading Phase: This is the first week (week 1) of the study, when patients receive their first (loading) dose of cetuximab only, in the vein. (2) Concurrent Phase: During this phase patients will be treated simultaneously (concurrently) with radiation therapy to their chest and cetuximab. Radiation is delivered 5 days a week, Monday to Friday for a total of 7 weeks (weeks 2-8). Cetuximab is delivered in the vein, weekly, during the weeks of radiation. (3) Recovery Phase: Patients receive no treatment during these next 3 weeks (weeks 9-11). This phase is designed to allow patients to recover from side effects before they start the last phase. (4) Consolidation Phase: The last phase. Patients will receive 3 doses of chemotherapy with docetaxel during this phase. Docetaxel is given intravenously every 21 days. Patients also receive weekly cetuximab during this phase. Cetuximab is delivered in a similar way as it was during the concurrent (second) phase of this study. In total, this phase lasts 6 weeks (weeks 12-18). Once the therapy treatment is completed, and if the patient's cancer did not get worse, follow up visits will include visits to their physician every three months for 2 years, then every 4 months for 2 years or more, as long as their cancer doesn't get worse (at which time they will be removed from the study).

Official Title
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Safety and Efficacy (Phase II) Study of Concurrent Cetuximab Plus Conformal Thoracic Radiotherapy in (Poor Prognosis) Patients With Inoperable or Unresectable, Locally Advanced Non-Small Cell Lung Cancer (LA - NSCLC)

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: Cetuximab
* Radiation: Conformal Thoracic Radiotherapy (CTRT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed inoperable or unresectable, LA-NSCLC (adenocarcinoma, squamous cell carcinoma or anaplastic large cell carcinoma or non-small cell otherwise not specified). Eligible Stages: Stages IIA through IIIA disease if it is felt that they are not candidates for possible resection, medically or otherwise. Stage IIIA (multi-station mediastinal lymph nodes) and stage IIIB disease without significant pleural effusion (metastases to contralateral mediastinal or supraclavicular lymph nodes) are also eligible. Age ≥ 70 OR Eastern Cooperative Oncology Group (ECOG) performance status (PS) = 2 at time of registration OR weight loss ≥ 5% in the preceding three months to the time of registration Must have measurable disease by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. When applicable, baseline measurements/evaluations must be obtained within 4 weeks prior to registration. Must have adequate bone marrow reserve as determined by the following laboratory values, obtained within 14 days prior to registration: White blood cell count (WBC) ≥ 4000/ul or absolute neutrophil count (ANC) ≥ 1000/ul Platelet count ≥ 100,000/ul Hemoglobin ≥ 8 gms/dl Adequate renal and liver function as determined by the following laboratory values, obtained within 14 days prior to registration: Serum creatinine ≤ 2.0 mg/dl or creatinine clearance ≥ 40 cc/min Bilirubin < 2.0 mg/dl serum glutamic oxaloacetic transaminase (SGOT) ≤ 2.5 times the upper limit of normal(ULN) Written, informed consent must be obtained prior to registration Women of childbearing potential (WOCBP) must use an accepted, effective method of contraception during the course of the study, in a manner such that risk of failure is minimized. Sexually active males enrolled should understand the risks to any sexual partner of childbearing potential; must also practice an effective method of contraception. WOCBP must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy; have a negative pregnancy test within 7 days prior to first receiving investigational product; be instructed to contact the Investigator immediately if they suspect they might be pregnant at any time during study participation. Investigator must immediately notify Bristol-Myers Squibb (BMS) in the event of a confirmed pregnancy in a patient participating in the study. If the pregnancy test is positive, the patient must not receive investigational product and must not be enrolled in the study. Exclusion Criteria: Must not have small cell carcinoma as part of the histological specimen Evidence of distant metastasis. History of a prior or concomitant malignancy in the past 3 years except for surgically cured basal cell carcinoma of the skin or carcinoma in situ of the cervix. Invasive malignancies, properly treated and currently disease-free > 3 years are allowed. Prior thoracic radiotherapy or epidermal growth factor receptor (EGFR) pathway targeting therapy. Prior systemic chemotherapy is allowed if received as therapy for an invasive malignancy, currently disease-free > 3 years Concomitant life threatening or uncontrolled serious medical illness such as cardiac disease (uncontrolled hypertension, arrhythmia, unstable angina, recent myocardial infarction, end stage congestive heart failure, cardiomyopathy with decreased ejection fraction), liver disease with significant hepatic insufficiency, kidney disease with significant renal insufficiency or organic brain syndrome.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cetuximab Plus Radiotherapy<br>Concurrent Cetuximab plus Conformal Thoracic Radiotherapy (CTRT). Patients were treated with definitive radiotherapy (70 Gy in 35 fractions, per our currently-existing institutional standard) with concurrent cetuximab followed by 3 cycles of consolidation docetaxel plus cetuximab. | Drug: Cetuximab<br>* Cetuximab dose: based on patient's actual weight. Loading phase dose of cetuximab is 400 mg/m2 IV administered over 120 minutes, on day 1 followed by; Concurrent phase, weekly infusion dose at 250 mg/m2 IV over 60 minutes, on days 8, 15, 22, 29, 36, 43, 50. Radiation will be accompanied by weekly Cetuximab. Weekly Cetuximab will start on 1st day of radiation (Day 8). So, total number of cetuximab administrations will vary from 7 to 8. Patients will have every other week complete blood counts (CBCs), differentials, and blood urea nitrogen (BUN) plus creatinine and Mg. If patient's ANC drops below 1,000 and/or the platelet count below 75,000 during CTRT, the corresponding, weekly dose of cetuximab will be omitted.<br>* Other names: immunotherapy;Radiation: Conformal Thoracic Radiotherapy (CTRT)<br>* Radiation will be accompanied by weekly Cetuximab. Weekly Cetuximab will start on 1st day of radiation (Day 8). So, total number of cetuximab administrations will vary from 7 to 8. Patients will have every other week CBCs, differentials, and BUN plus creatinine and Mg. If patient's ANC drops below 1,000 and/or the platelet count below 75,000 during CTRT, the corresponding, weekly dose of cetuximab will be omitted. Radiation therapy will begin on day 8 (with window of ± 3 days). Adequate hematologic profile (ANC >1,000 and platelets >75,000) required. Patient may be delayed for a max. of 2 weeks. If > 2 week delay occurs, patient will come off study.<br>* Other names: Radiotherapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Progression Free Survival (PFS) | Progression Free Survival is defined as the interval between the date of the first cetuximab administration and the date of objective progression of disease. Progression was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria. Progressive Disease (PD): Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. | Up to 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Overall Survival (OS) | Overall survival is defined as the time from randomization until death from any cause. | Up to 36 months | 
| Overall Response Rate (ORR) | ORR = Complete Response (CR) + Partial Response (CR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.0. Complete Response: Disappearance of all target lesions; Partial Response: At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. | Up to 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lung, Thoracic, Immunotherapy, Radiotherapy, LA - NSCLC, Non-Small Cell Lung Cancer