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 to IVA	Drug: Cetuximab, Cisplatin, Doxorubicin & Cyclophosphamide	Phase 2


Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: No masking 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)

Resource links provided by NLM:

MedlinePlus related topics: Thymus Cancer

Drug Information available for: Cyclophosphamide Cisplatin Doxorubicin 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 ]

Secondary Outcome Measures:

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


Estimated Enrollment:	18
Study Start Date:	December 2009
Estimated Study Completion Date:	December 2018
Estimated Primary Completion Date:	December 2018 (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 (Adult, Senior)
Sexes Eligible for Study:	All
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, 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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations


United States, California
City of Hope Medical Center
Duarte, California, United States, 91010-3000
United States, New Jersey
Memorial Sloan Kettering at Basking Ridge
Basking Ridge, New Jersey, United States, 07920
United States, New York
Memorial Sloan Kettering Cancer Center @ Suffolk
Commack, New York, United States, 11725
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Memorial Sloan Kettering at Mercy Medical Center
Rockville Centre, New York, United States
Memorial Sloan Kettering Cancer Center at Phelps Memorial Hospital Center
Sleepy Hollow, New York, United States, 10591
Memorial Sloan Kettering West Harrison
West Harrison, New York, United States, 10604
United States, Texas
Md Anderson Cancer Center
Houston, Texas, United States, 77030

Sponsors and Collaborators

Memorial Sloan Kettering Cancer Center

Eli Lilly and Company

M.D. Anderson Cancer Center

City of Hope National Medical 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


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 4, 2017

Keywords provided by Memorial Sloan Kettering Cancer Center:


Cetuximab Cisplatin Cyclophosphamide 09-038

Additional relevant MeSH terms:


Carcinoma Thymoma Thymus Neoplasms Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Neoplasms, Complex and Mixed Thoracic Neoplasms Neoplasms by Site Lymphatic Diseases Liposomal doxorubicin Cisplatin Doxorubicin Cyclophosphamide	Cetuximab Antineoplastic Agents Antibiotics, Antineoplastic Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Myeloablative Agonists

ClinicalTrials.gov processed this record on June 23, 2017