Radiation Therapy Plus Doxorubicin in Treating Patients With Resectable Primary or Recurrent Retroperitoneal Soft Tissue Sarcoma

Sponsor

M.D. Anderson Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00004123

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arm

147

Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining radiation therapy with chemotherapy may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of radiation therapy plus doxorubicin in treating patients who have resectable primary or recurrent peritoneal soft tissue sarcoma.

Condition or Disease	Intervention/Treatment	Phase
Sarcoma	Drug: Doxorubicin hydrochloride (DOX) Procedure: Conventional surgery Radiation: Intraoperative radiation therapy (IORT) Radiation: Radiation Therapy (RT)	Phase 1

Detailed Description

OBJECTIVES: I. Determine the toxicity and maximum tolerated dose of preoperative external beam radiotherapy when combined with doxorubicin and followed by intraoperative radiotherapy in patients with resectable primary or recurrent soft tissue sarcoma of the retroperitoneum.

Assess radiologic and pathologic response in patients treated with this preoperative regimen.

OUTLINE: This is a dose-escalation study of external beam radiotherapy. Patients receive doxorubicin IV bolus followed immediately by doxorubicin IV over 4 days every week for 5 weeks concurrently with external beam radiotherapy 5 days a week for 4 weeks. Patients with stable or responding disease undergo surgical resection of primary tumor and all adjacent gross disease approximately 6 weeks after completion of chemoradiotherapy. Patients receive intraoperative radiotherapy (IORT) to the tumor bed if all gross disease has been resected and if the area of maximal tumor adherence to the retroperitoneum can be encompassed within a single IORT field (maximum 15 cm). Cohorts of 3-6 patients receive escalating doses of external beam radiotherapy until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 30% of patients experience grade 3 or worse dose-limiting toxicity.

PROJECTED ACCRUAL: A total of 15-45 patients will be accrued for this study.

Study Design

Study Type:

Interventional

Actual Enrollment :

36 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I Study of Preoperative Chemoradiation and Intraoperative Radiation Therapy in the Treatment of Retroperitoneal Sarcoma

Study Start Date :

Jul 1, 1997

Actual Primary Completion Date :

Jul 1, 2001

Actual Study Completion Date :

Oct 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: RT + DOX + IORT Preoperative external beam radiotherapy (RT) combined with doxorubicin (DOX) and followed by intraoperative radiotherapy (IORT); dose-escalation study of external beam radiotherapy.	Drug: Doxorubicin hydrochloride (DOX) Doxorubicin IV bolus followed immediately by IV over 4 days every week for 5 weeks concurrently with external beam radiotherapy 5 days a week for 4 weeks. Other Names: Rubex Adriamycin Procedure: Conventional surgery Surgical resection of primary tumor and all adjacent gross disease approximately 6 weeks after chemoradiotherapy Radiation: Intraoperative radiation therapy (IORT) Intraoperative radiotherapy (IORT) to tumor bed if all gross disease has been resected and if area of maximal tumor adherence to retroperitoneum can be encompassed within a single IORT field (maximum 15 cm). Radiation: Radiation Therapy (RT) 5 days a week for 4 weeks Other Names: RT Radialtherapy

Arm

Intervention/Treatment

Experimental: RT + DOX + IORT

Preoperative external beam radiotherapy (RT) combined with doxorubicin (DOX) and followed by intraoperative radiotherapy (IORT); dose-escalation study of external beam radiotherapy.

Drug: Doxorubicin hydrochloride (DOX)

Doxorubicin IV bolus followed immediately by IV over 4 days every week for 5 weeks concurrently with external beam radiotherapy 5 days a week for 4 weeks.

Other Names:

Rubex

Adriamycin

Procedure: Conventional surgery

Surgical resection of primary tumor and all adjacent gross disease approximately 6 weeks after chemoradiotherapy

Radiation: Intraoperative radiation therapy (IORT)

Intraoperative radiotherapy (IORT) to tumor bed if all gross disease has been resected and if area of maximal tumor adherence to retroperitoneum can be encompassed within a single IORT field (maximum 15 cm).

Radiation: Radiation Therapy (RT)

5 days a week for 4 weeks

Other Names:

Radialtherapy

Outcome Measures

Primary Outcome Measures

Maximum Tolerated Dose (MTD) of Preoperative External Beam Radiotherapy, Doxorubicin + Intraoperative Radiotherapy [6 weeks]
The MTD is defined as the dose at which 30% of patients experience grade 3 or worse dose-limiting toxicity

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS: Histologically or cytologically proven resectable primary or recurrent soft tissue sarcoma of the retroperitoneum Greatest dimension of the 3-dimensional assessment of tumor size must be 5-35 cm Grade 2 or 3, including dedifferentiated liposarcoma and retroperitoneal recurrences of gastrointestinal leiomyosarcoma

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 70-100% Zubrod 0 or 1 Life expectancy: Not specified Hematopoietic: Absolute neutrophil count greater than 2,000/mm3 Platelet count at least 100,000/mm3 Hepatic: Not specified Renal: Renal function normal Creatinine less than 1.6 mg/dL Gastrointestinal: Must maintain adequate oral nutrition (90-100% of estimated need for calories and protein) and be free of nausea and vomiting prior to radiotherapy (feeding tube allowed) Other: Prior malignancy allowed at the discretion of the protocol investigator No other serious uncontrolled medical condition Not pregnant or nursing Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: Not specified Endocrine therapy: Not specified Radiotherapy: No prior abdominal radiotherapy Surgery: See Disease Characteristics