Preoperative Treatment of Patients With High Risk Thymoma

Thymoma Clinical Trial

Official title:

Phase II Study of Trimodality Therapy for Patients With Thymoma or Thymic Carcinoma at Significant Risk for Recurrence

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00387868
• Other study ID #: VHS07.0006a
• Status: Completed
• Phase: Phase 2
• First received: October 11, 2006
• Last updated: December 8, 2014
• Start date: October 2006
• Est. completion date: November 2014

Study information

• Verified date: December 2014
• Source: Valley Health System
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

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.

Other known NCT identifiers

• NCT00509522

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: November 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Thymoma
• Thymus Neoplasms

Intervention

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

Procedure:
• Surgical Resection
Resection will take place 4-8 weeks after completion of radiotherapy.

Radiation:
• Concurrent Radiotherapy
Preoperative External Beam Radiotherapy

Locations

Country	Name	City	State
Canada	University of Toronto	Toronto	Ontario
United States	Valley Health System - The Valley Hospital	Ridgewood	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Valley Health System

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		16 weeks	No
Secondary	Radiographic response to preoperative chemoradiotherapy by comparing pre and post treatment CT scans.		16 weeks	No
Secondary	Rate of complete resection following preoperative chemoradiotherapy as determined by pathologic examination of the specimen(s).		1-5 weeks	No
Secondary	Toxicities throughout the study treatment.		5 years	Yes
Secondary	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		10 years	Yes
Secondary	Immunohistochemical assessment of relevant markers before and after chemoradiation (EGFR, p53,and Ki-67).		10-12 years	No
Secondary	Blood-based correlative studies: genetic polymorphisms (EGFR, DNA repair, inflammatory gene pathways) and serologic analysis (EGFR, VEGF, bFGF, pro-MMP2 levels)		8-10 years	No
Secondary	Recurrence rates and failure patterns following the treatment regimen.		5-7 years	Yes