Preoperative Treatment of Patients With High Risk Thymoma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Valley Health System
ClinicalTrials.gov Identifier:
NCT00387868
First received: October 11, 2006
Last updated: March 27, 2014
Last verified: March 2014
  Purpose

This is a phase II study for patients with thymoma or thymic carcinoma thought to be at significant risk for recurrence following surgical removal. This study involves the use of combined chemotherapy and radiation therapy prior to surgery, in hopes of increasing the chances of complete resection. The chemoradiotherapy protocol is one which has been used extensively for other diseases, and the side effects are therefore well-documented. Patients with thymomas thought to be at significant risk for recurrence (by x-ray and pathology criteria) will be allowed to participate, and will undergo combined chemotherapy with radiation to the chest followed by surgical removal of the tumor and postoperative chemotherapy. The main outcome measured will be the rate of pathological complete response (e.g. no active tumor in the resected specimen) to the preoperative treatment. Patients will receive postoperative treatment based on surgical and pathologic criteria.


Condition Intervention Phase
Thymoma
Drug: cisplatin and etoposide
Procedure: Surgical Resection
Radiation: Concurrent Radiotherapy
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: Phase II Study of Trimodality Therapy for Patients With Thymoma or Thymic Carcinoma at Significant Risk for Recurrence

Resource links provided by NLM:


Further study details as provided by Valley Health System:

Primary Outcome Measures:
  • To determine the complete pathologic response rate to peroperative cisplatin and etoposide given concurrently with radiation in patients with thymoma thought to be at high risk for recurrence [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Radiographic response to preoperative chemoradiotherapy by comparing pre and post treatment CT scans. [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • Rate of complete resection following preoperative chemoradiotherapy as determined by pathologic examination of the specimen(s). [ Time Frame: 1-5 weeks ] [ Designated as safety issue: No ]
  • Toxicities throughout the study. [ Time Frame: 15 years ] [ Designated as safety issue: Yes ]
  • The role of PET in predicting resectability, Masaoka stage and histologic type, as well as the response to preoperative chemoradiotherapy by comparing pre and post treatment PET scans [ Time Frame: 10 years ] [ Designated as safety issue: Yes ]
  • Immunohistochemical assessment of relevant markers before and after chemoradiation (EGFR, p53,and Ki-67). [ Time Frame: 10-12 years ] [ Designated as safety issue: No ]
  • Blood-based correlative studies: genetic polymorphisms (EGFR, DNA repair, inflammatory gene pathways) and serologic analysis (EGFR, VEGF, bFGF, pro-MMP2 levels) [ Time Frame: 8-10 years ] [ Designated as safety issue: No ]
  • Recurrence rates and failure patterns following the treatment regimen. [ Time Frame: 5-7 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 30
Study Start Date: October 2006
Estimated Study Completion Date: October 2021
Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Registration
Cisplatin, Etoposide & concurrent radiotherapy
Drug: cisplatin and etoposide
Cisplatin: 50mg/m2 - administered on days 1,8,29&36 Etoposide: 50 mg/m2 - administered on days 1-5 & 29-33
Radiation: Concurrent Radiotherapy
Preoperative External Beam Radiotherapy
Surgical Resection
No distant Progression post Registration Arm
Procedure: Surgical Resection
Resection will take place 4-8 weeks after completion of radiotherapy.
Post Resection
Assessment post surgical procedure to determine if at higher risk of recurrence or if complete resection could not be achieved.
Drug: cisplatin and etoposide
Cisplatin: 50mg/m2 - administered on days 1,8,29&36 Etoposide: 50 mg/m2 - administered on days 1-5 & 29-33

Detailed Description:

Past experience has suggested that the ability to completely remove the thymoma using surgery is important in preventing recurrence. Strategies which would help the surgeon's ability to completely remove the tumor therefore need to be investigated.

This study represents a multi-institutional, phase II pilot trial of preoperative chemoradiotherapy followed by surgical resection and postoperative chemotherapy for patients with invasive thymoma or thymic carcinoma at significant risk for recurrence. We hypothesize that this strategy will be well-tolerated and produce response and resectability rates exceeding those previously published involving surgical resection alone, or preoperative chemotherapy followed by surgery. Patients with locally advanced thymoma, based on radiographic and biopsy criteria, will undergo pretreatment computed tomography (CT) scan and positron emission tomography (PET) followed by concurrent (simultaneous) chemotherapy (cisplatin and etoposide) and radiation. After this therapy, patients will be reassessed using computed tomography (CT) and PET, and undergo surgical resection of their tumors. Following resection, patients will be either observed, or treated with postoperative chemotherapy, or chemotherapy and radiation. Correlative genomic, serologic and pathologic studies will also be performed.

  Eligibility

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

Inclusion Criteria:

  • Biopsy-proven thymoma or thymic carcinoma.
  • Invasive thymoma determined by specific radiographic criteria determined by CT scan.
  • Acceptable kidney, liver, bone marrow, and respiratory functions.
  • Karnofsy performance status greater than 80%.
  • Patients must have a CT of the chest with IV contrast within 60 days of enrollment.
  • Tumors larger than 8cm in greatest diameter on CT scan.
  • For tumors 5-8cm in greatest diameter on CT scan, one or more of the following radiographic criteria must also be present on IV contrast CT Scan:
  • Multifocal calcification
  • Heterogeneous appearance
  • Irregular of scalloped borders
  • Obvious great vessel invasion or encirclement

Exclusion Criteria:

  • Considered unable to medically tolerate surgical resection at the time of initial presentation.
  • Radiographic evidence of stage IVA thymoma.
  • Pretreatment biopsy showing WHO type A thymoma unless obvious great vessel invasion/encirclement is present on CT scan.
  • Previous radiation therapy to the chest which would preclude the administration of radiation.
  • Patents receiving other investigational drugs.
  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: NCT00387868

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, New Jersey
Valley Health System - The Valley Hospital
Ridgewood, New Jersey, United States, 07450
United States, Texas
Methodist Hospital
Houston, Texas, United States, 77030
Canada, Ontario
University of Toronto
Toronto, Ontario, Canada, M5G2C4
Sponsors and Collaborators
Valley Health System
Investigators
Principal Investigator: Robert Korst, MD Valley Health Systems/ The Valley Hospital
  More Information

No publications provided by Valley Health System

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Valley Health System
ClinicalTrials.gov Identifier: NCT00387868     History of Changes
Obsolete Identifiers: NCT00509522
Other Study ID Numbers: VHS07.0006a
Study First Received: October 11, 2006
Last Updated: March 27, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Valley Health System:
Thymoma
Thymic carcinoma
Preoperative chemotherapy and radiation
Response rate

Additional relevant MeSH terms:
Thymoma
Neoplasms, Complex and Mixed
Neoplasms by Histologic Type
Neoplasms
Thymus Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lymphatic Diseases
Etoposide phosphate
Cisplatin
Etoposide
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on July 24, 2014