Doxorubicin Plus External-Beam Radiation Therapy in Treating Patients With Soft Tissue Sarcoma

Sponsor

M.D. Anderson Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00004109

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arm

157

Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

PURPOSE: Phase I trial to study the effectiveness of doxorubicin plus external-beam radiation therapy in treating patients who have soft tissue sarcoma.

Condition or Disease	Intervention/Treatment	Phase
Sarcoma	Drug: Doxorubicin Hydrochloride Radiation: Radiation Therapy (RT)	Phase 1

Detailed Description

OBJECTIVES: I. Determine the toxicity and maximum tolerated dose of doxorubicin when combined with external beam radiotherapy in patients with high risk soft tissue sarcomas of the extremity or trunk. II. Assess the radiographic and pathologic response rates to this preoperative regimen in the subset of these patients with measurable disease.

OUTLINE: This is a dose escalation study of doxorubicin. Patients receive doxorubicin intravenous (IV) bolus followed immediately by doxorubicin IV over 4 days every week for 5 weeks in the absence of unacceptable toxicity. Patients with measurable disease receive external beam radiotherapy 5 days a week for 5 weeks concurrently with doxorubicin treatment. Patients with measurable disease undergo surgical resection of the residual mass 4-7 weeks following completion of chemoradiation. Patients who have no measurable disease and have undergone prereferral excision undergo surgical resection of the prior surgical scar and tumor bed followed by external beam radiotherapy 5 days a week for 5 weeks. Cohorts of 3 patients receive escalating doses of doxorubicin until the maximum tolerated dose (MTD) is determined. Patients are followed every 3 months for 3 years, every 4 months for 2 years, and then annually for 5 years.

PROJECTED ACCRUAL: A maximum of 30 patients will be accrued for this study at a rate of 5-6 patients per month.

Study Design

Study Type:

Interventional

Actual Enrollment :

30 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I Study of Preoperative Concurrent Chemoradiation for High-Risk Extremity and Trunk Soft Tissue Sarcomas

Study Start Date :

Mar 1, 1998

Actual Primary Completion Date :

Sep 1, 2001

Actual Study Completion Date :

Apr 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Doxorubicin + External-Beam RT	Drug: Doxorubicin Hydrochloride Doxorubicin dose will not exceed 20 mg/m2 per week IV over 4 days every week for 5 weeks Other Names: doxorubicin Radiation: Radiation Therapy (RT) External-beam radiotherapy at a dose of 50 Gy (2.0 x 25 fractions, weeks 1-5). Other Names: RT Radialtherapy

Arm

Intervention/Treatment

Experimental: Doxorubicin + External-Beam RT

Drug: Doxorubicin Hydrochloride

Doxorubicin dose will not exceed 20 mg/m2 per week IV over 4 days every week for 5 weeks

Other Names:

doxorubicin

Radiation: Radiation Therapy (RT)

External-beam radiotherapy at a dose of 50 Gy (2.0 x 25 fractions, weeks 1-5).

Other Names:

Radialtherapy

Outcome Measures

Primary Outcome Measures

Maximum Tolerated Dose (MTD) [Continousouly during 5 weeks treatment]
MTD of doxorubicin intravenous (IV) based on presence of dose limiting toxicities. For dose-finding purposes, a dose-limiting toxicity (DLT) was defined as grade 3 or greater treatment-related cutaneous toxicity

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients must have cytologic or histologic proof of large (>5 mc), Grade III, resectable soft tissue sarcoma of the extremity or trunk (AJCC Stage IIIB). Patients with The American Joint Committee on Cancer (AJCC) Stage IIB tumors (Grade II) greater than 8 cms will also be eligible.
Patients may have measurable or non-measurable disease (C/P pre-referral excision).
Patients may have had prior doxorubicin (up to a total doxorubicin dose of 450 mg/m2).
Patients may have a prior history of malignancy (at the discretion of the Principal Investigator).
Patients must have Karnofsky Point Scale (P.S.)> of >70 or Xubrod P.S. of 0 or 1.
Patients must have: Absolute neutrophil count (ANC) > 1,500 cells/mm; platelet count > 100,000 platelets/ml; serum creatinine <1.8 mg/dl, aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT) < 3 times normal, total bilirubin < 1.5mg/dl; for patients with cumulative Adriamycin 450 mg/M2, EF >50%.
Women of childbearing potential must not be pregnant or breast feeding and must practice adequate contraception.

Exclusion Criteria:

Patients must not have had prior radiation therapy (XRT) in the area of the primary tumor, and the anticipated XRT field must not include the perineum, scrotum, or vaginal introitus.
Patients with uncontrolled coexisting medical conditions are excluded.
Patient must not be pregnant or brest feeding.