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

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT01025089

Collaborator

Eli Lilly and Company (Industry), M.D. Anderson Cancer Center (Other), City of Hope National Medical Center (Other)

Enrollment

Locations

Arm

168

Duration (Months)

2.3

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Thymoma Thymic Carcinoma Clinical Masaoka Stage II to IVA	Drug: Cetuximab, Cisplatin, Doxorubicin & Cyclophosphamide	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

18 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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)

Study Start Date :

Dec 1, 2009

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Cetuximab, Cisplatin, Doxorubicin & Cyclophosphamide 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.

Arm

Intervention/Treatment

Experimental: 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.

Drug: Cetuximab, Cisplatin, Doxorubicin & Cyclophosphamide

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.

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope Medical Center	Duarte	California	United States	91010-3000
2	Memorial Sloan Kettering at Basking Ridge	Basking Ridge	New Jersey	United States	07920
3	Memorial Sloan Kettering Cancer Center @ Suffolk	Commack	New York	United States	11725
4	Memorial Sloan Kettering West Harrison	Harrison	New York	United States	10604
5	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
6	Memorial Sloan Kettering at Mercy Medical Center	Rockville Centre	New York	United States
7	Memorial Sloan Kettering Cancer Center at Phelps Memorial Hospital Center	Sleepy Hollow	New York	United States	10591
8	Md Anderson Cancer Center	Houston	Texas	United States	77030