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

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

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.

Study Overview

• Status: Completed
• Conditions: Sarcoma
• Intervention / Treatment: Drug: Doxorubicin hydrochloride (DOX); Procedure: Conventional surgery; Radiation: Intraoperative radiation therapy (IORT); Radiation: Radiation Therapy (RT)

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. II. 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 Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030-4009
      • University of Texas - MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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: Adriamycin; Rubex; 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

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Peter W. Pisters, MD, M.D. Anderson Cancer Center

Publications and helpful links

Helpful Links

• UT MD Anderson Cancer Center Website

Study record dates

Study Major Dates

• Study Start: July 1, 1997
• Primary Completion (Actual): July 1, 2001
• Study Completion (Actual): October 1, 2009

Study Registration Dates

• First Submitted: December 10, 1999
• First Submitted That Met QC Criteria: March 22, 2004
• First Posted (Estimate): March 23, 2004

Study Record Updates

• Last Update Posted (Estimate): July 30, 2012
• Last Update Submitted That Met QC Criteria: July 27, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: adult leiomyosarcoma; adult liposarcoma; recurrent adult soft tissue sarcoma; stage III adult soft tissue sarcoma; stage II adult soft tissue sarcoma
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Doxorubicin; Liposomal doxorubicin
• Other Study ID Numbers: ID95-225; P30CA016672 (U.S. NIH Grant/Contract); MDA-ID-95225 (Other Identifier: UT MD Anderson Cancer Center); NCI-G99-1606; CDR0000067350 (Registry Identifier: NCI PDQ)