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

Primary Purpose

Sarcoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Doxorubicin Hydrochloride
Radiation Therapy (RT)
Sponsored by
M.D. Anderson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sarcoma focused on measuring stage III adult soft tissue sarcoma, recurrent adult soft tissue sarcoma, Doxorubicin, External-Beam RT, XRT, cancer, PREOPERATIVE CONCURRENT CHEMORADIATION, EXTREMITY SOFT TISSUE SARCOMAS, TRUNK SOFT TISSUE SARCOMAS, Concurrent Chemoradiation, Surgical Resection, Localized Extremity Soft Tissue Sarcomas, Body Wall Soft Tissue Sarcomas

Eligibility Criteria

16 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • University of Texas - MD Anderson Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Doxorubicin + External-Beam RT

Arm Description

Outcomes

Primary Outcome Measures

Maximum Tolerated Dose (MTD)
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

Secondary Outcome Measures

Full Information

First Posted
December 10, 1999
Last Updated
August 1, 2012
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00004109
Brief Title
Doxorubicin Plus External-Beam Radiation Therapy in Treating Patients With Soft Tissue Sarcoma
Official Title
A Phase I Study of Preoperative Concurrent Chemoradiation for High-Risk Extremity and Trunk Soft Tissue Sarcomas
Study Type
Interventional

2. Study Status

Record Verification Date
August 2012
Overall Recruitment Status
Completed
Study Start Date
March 1998 (undefined)
Primary Completion Date
September 2001 (Actual)
Study Completion Date
April 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sarcoma
Keywords
stage III adult soft tissue sarcoma, recurrent adult soft tissue sarcoma, Doxorubicin, External-Beam RT, XRT, cancer, PREOPERATIVE CONCURRENT CHEMORADIATION, EXTREMITY SOFT TISSUE SARCOMAS, TRUNK SOFT TISSUE SARCOMAS, Concurrent Chemoradiation, Surgical Resection, Localized Extremity Soft Tissue Sarcomas, Body Wall Soft Tissue Sarcomas

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Doxorubicin + External-Beam RT
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Doxorubicin Hydrochloride
Other Intervention Name(s)
doxorubicin
Intervention Description
Doxorubicin dose will not exceed 20 mg/m2 per week IV over 4 days every week for 5 weeks
Intervention Type
Radiation
Intervention Name(s)
Radiation Therapy (RT)
Other Intervention Name(s)
RT, Radialtherapy
Intervention Description
External-beam radiotherapy at a dose of 50 Gy (2.0 x 25 fractions, weeks 1-5).
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose (MTD)
Description
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
Time Frame
Continousouly during 5 weeks treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter W. Pisters, MD
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
University of Texas - MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030-4009
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.mdanderson.org
Description
UT MD Anderson Cancer Center Website

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

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