Chemotherapy Plus Cetuximab Followed by Surgical Resection in Patients With Locally Advanced or Recurrent Thymoma or Thymic Carcinoma

Study Overview
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Brief Summary
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The main purpose of this study is to find out the good and the bad effects that the combination of cetuximab with the traditional chemotherapy regimen of cisplatin, doxorubicin, and cyclophosphamide has when given to patients with later stage thymoma or thymic carcinoma before surgery. The physicians will also look at changes in genes in the tumor that may relate to the effectiveness of cetuximab

Official Title
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A Phase II Trial of Chemotherapy Plus Cetuximab Followed by Surgical Resection in Patients With Locally Advanced or Recurrent Thymoma or Thymic Carcinoma (BMS #CA225-331/Lilly Trial Alias I4E-US-X007)

Conditions
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Thymoma, Thymic Carcinoma, Clinical Masaoka Stage II to IVA

Intervention / Treatment
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* Drug: Cetuximab, Cisplatin, Doxorubicin & Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age>18 Karnofsky Performance Status (KPS) ≥ 70 Newly diagnosed or recurrent thymoma - WHO A, AB, B1, B2, or B340, or thymic carcinoma pathologically confirmed at MSKCC, MDACC or City of Hope No prior chemotherapy, radiotherapy, or surgical therapy (other than for diagnostic biopsy) for thymoma No prior treatment with cetuximab Clinical Masaoka Stage II (>5cm), III, or IVA(See Appendix B), including suspected invasion of mediastinum, pericardium, lung, great vessels or chest wall, and/or pleural metastases Normal marrow function: leukocytes ≥ 4,000/μl, absolute neutrophil count ≥ 1,500/μl, platelets ≥ 160,000/μl Adequate renal function, with creatinine ≤ 1.3 mg/dl or calculated creatinine clearance ≥60ml/min by Cockcroft and Gault equation using parameters of age, weight (kg), and baseline serum creatinine (mg/dl) Adequate hepatic function: Total bilirubin ≤1.5 mg/dl, AST ≤1.5X UNL, alkaline phosphatase ≤1.5 UN Signed informed consent Effective contraception Medically operable Exclusion Criteria: Evidence of distant metastatic disease (Masaoka stage IVB) Thymic carcinoid Patients must not be receiving any other investigational agents Concurrent or prior malignancy in the last 5 years other than non-melanoma skin cancer and in-situ carcinoma of the cervix Known HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with the study drugs. Patients on medications known to alter CYP3A4 Pregnant or breastfeeding women

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, Cisplatin, Doxorubicin & Cyclophosphamide<br>This is a multicenter, open-label phase II trial of neoadjuvant chemotherapy and concurrent cetuximab in patients with clinical Masaoka stage II-IVA thymoma or thymic carcinoma.. Patients will initially receive weekly cetuximab for 4 weeks to assess tumor response to cetuximab alone. Patients will then undergo weekly cetuximab along with concurrent CAP for 4 cycles. At the completion of this regimen, patients will undergo surgical resection and the specimen will be evaluated for CPR. | Drug: Cetuximab, Cisplatin, Doxorubicin & Cyclophosphamide<br>* Patients will receive single agent cetuximab infusion starting with a 400mg/m2 IV loading dose on day 1 of week 1, followed by weekly infusions (250mg/m2) on day 1 of weeks 2 3, and 4. Patients will receive single agent cetuximab infusion starting with a 400mg/m2 IV loading dose on day 1 of week 1, followed by weekly infusions (250mg/m2) on day 1 of weeks 2 3, and 4. Patients who have completed the neo-adjuvant treatment regimen, who have no evidence of distant progression, and who are medically operable will proceed to surgical resection within 6 weeks of the last infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the frequency of complete pathologic response to neo-adjuvant therapy with cisplatin, doxorubicin, cyclophosphamide (CAP) and cetuximab in patients with clinical Masaoka stage II-IVa thymoma and thymic carcinomas. |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the toxicity (CTCAE v.3) of neo-adjuvant therapy with CAP and cetuximab |  | 2 years | 
| To measure the radiographic response rate to cetuximab alone after 4 weeks |  | 4 weeks | 
| To determine the radiographic response rate to CAP and cetuximab |  | 2 years | 
| To determine the complete resection rate (R0) after neo-adjuvant therapy with CAP and cetuximab |  | 2 years | 
| To correlate percentage of pathologic response to unidimensional and volumetric radiographic response |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cetuximab, Cisplatin, Cyclophosphamide, 09-038