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

Purpose

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	Intervention	Phase
Thymoma Thymic Carcinoma. Clinical Masaoka Stage II-IVA	Drug: Cetuximab, Cisplatin, Doxorubicin & Cyclophosphamide	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: 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

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Cyclophosphamide Cisplatin Doxorubicin Doxorubicin hydrochloride Cetuximab

U.S. FDA Resources

Further study details as provided by Memorial Sloan-Kettering Cancer Center:

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. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To determine the toxicity (CTCAE v.3) of neo-adjuvant therapy with CAP and cetuximab [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
To measure the radiographic response rate to cetuximab alone after 4 weeks [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
To determine the radiographic response rate to CAP and cetuximab [ Time Frame: 2 years ] [ Designated as safety issue: No ]
To determine the complete resection rate (R0) after neo-adjuvant therapy with CAP and cetuximab [ Time Frame: 2 years ] [ Designated as safety issue: No ]
To correlate percentage of pathologic response to unidimensional and volumetric radiographic response [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment:	28
Study Start Date:	December 2009
Estimated Study Completion Date:	December 2014
Estimated Primary Completion Date:	December 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.

Arms

Assigned Interventions

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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 or MDACC
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT01025089

Contacts

Contact: James Huang, MD	646-888-3055
Contact: Gregory Riely, MD	212-639-3042

Locations

United States, New Jersey
Memorial Sloan-Kettering at Basking Ridge	Recruiting
Basking Ridge, New Jersey, United States, 07920
Contact: James Huang, MD
United States, New York
Memorial Sloan-Kettering Cancer Center @ Suffolk	Recruiting
Commack, New York, United States, 11725
Contact: James Huang, MD
Memorial Sloan Kettering Cancer Center	Recruiting
New York, New York, United States, 10065
Contact: James Huang, MD 646-888-3055
Principal Investigator: James Huang, MD
Memorial Sloan-Kettering at Mercy Medical Center	Recruiting
Rockville Centre, New York, United States
Contact: James Huang, MD
Memorial Sloan-Kettering Cancer Center at Phelps Memorial Hospital Center	Recruiting
Sleepy Hollow, New York, United States, 10591
Contact: James Huang, MD
United States, Texas
Md Anderson Cancer Center	Not yet recruiting
Houston, Texas, United States, 77030
Contact: George Simon, MD
Principal Investigator: George Simon, MD

Sponsors and Collaborators

Memorial Sloan-Kettering Cancer Center

Bristol-Myers Squibb

M.D. Anderson Cancer Center

Investigators

Principal Investigator:

James Huang, MD

Memorial Sloan-Kettering Cancer Center

More Information

Additional Information:

Memorial Sloan-Kettering Cancer Center This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:	NCT01025089 History of Changes
Other Study ID Numbers:	09-038
Study First Received:	December 2, 2009
Last Updated:	April 25, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:

Cetuximab
Cisplatin
Cyclophosphamide
09-038

Additional relevant MeSH terms:

Carcinoma
Thymoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Complex and Mixed
Thymus Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lymphatic Diseases
Cetuximab
Cisplatin
Cyclophosphamide
Doxorubicin

Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Antibiotics, Antineoplastic

ClinicalTrials.gov processed this record on May 23, 2013