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

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)

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

Study Overview

• Status: Active, not recruiting
• Conditions: Thymic Carcinoma; Thymoma; Clinical Masaoka Stage II to IVA
• Intervention / Treatment: Drug: Cetuximab, Cisplatin, Doxorubicin & Cyclophosphamide

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: M.D. Anderson Cancer Center; Eli Lilly and Company; City of Hope National Medical Center
• Investigators: Principal Investigator: James Huang, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan-Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start: December 1, 2009
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: December 2, 2009
• First Submitted That Met QC Criteria: December 2, 2009
• First Posted (Estimated): December 3, 2009

Study Record Updates

• Last Update Posted (Actual): May 31, 2023
• Last Update Submitted That Met QC Criteria: May 30, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Cisplatin; Cyclophosphamide; Cetuximab; 09-038
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Lymphatic Diseases; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Thoracic Neoplasms; Neoplasms, Complex and Mixed; Carcinoma; Thymoma; Thymus Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Cyclophosphamide; Doxorubicin; Cetuximab
• Other Study ID Numbers: 09-038