Preoperative Treatment of Patients With High Risk Thymoma

Sponsor

Valley Health System (Other)

Overall Status

Completed

CT.gov ID

NCT00387868

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

10.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Thymoma	Drug: cisplatin and etoposide Procedure: Surgical Resection Radiation: Concurrent Radiotherapy	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

21 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (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

Study Start Date :

Oct 1, 2006

Actual Primary Completion Date :

Oct 1, 2014

Actual Study Completion Date :

Nov 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Other: 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
Other: Surgical Resection No distant Progression post Registration Arm	Procedure: Surgical Resection Resection will take place 4-8 weeks after completion of radiotherapy.
Other: 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

Arm

Intervention/Treatment

Other: 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

Other: Surgical Resection

No distant Progression post Registration Arm

Procedure: Surgical Resection

Resection will take place 4-8 weeks after completion of radiotherapy.

Other: 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

Outcome Measures

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 [16 weeks]

Secondary Outcome Measures

Radiographic response to preoperative chemoradiotherapy by comparing pre and post treatment CT scans. [16 weeks]
Rate of complete resection following preoperative chemoradiotherapy as determined by pathologic examination of the specimen(s). [1-5 weeks]
Toxicities throughout the study treatment. [5 years]
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]
Immunohistochemical assessment of relevant markers before and after chemoradiation (EGFR, p53,and Ki-67). [10-12 years]
Blood-based correlative studies: genetic polymorphisms (EGFR, DNA repair, inflammatory gene pathways) and serologic analysis (EGFR, VEGF, bFGF, pro-MMP2 levels) [8-10 years]
Recurrence rates and failure patterns following the treatment regimen. [5-7 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.