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

Phase 2

Active, not recruiting

Brief Summary: 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

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Cetuximab, Cisplatin, Doxorubicin & Cyclophosphamide	Cetuximab, Cisplatin, Doxorubicin & Cyclophosphamide	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
To determine the toxicity (CTCAE v.3) of neo-adjuvant therapy with 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
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

Locations (8): Memorial Sloan Kettering Cancer Center at Phelps Memorial Hospital Center
🇺🇸
Sleepy Hollow, New York, United States
Memorial Sloan Kettering at Basking Ridge
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Basking Ridge, New Jersey, United States
Memorial Sloan Kettering Cancer Center @ Suffolk
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Commack, New York, United States
City of Hope Medical Center
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Duarte, California, United States
Md Anderson Cancer Center
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Houston, Texas, United States
Memorial Sloan Kettering West Harrison
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Harrison, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸
New York, New York, United States
Memorial Sloan Kettering at Mercy Medical Center
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Rockville Centre, New York, United States