Combination Chemotherapy in Treating Patients With Sarcoma

A Pilot Study for Soft Tissue Sarcoma

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.

PURPOSE: This clinical trial is studying how well combination chemotherapy works in treating patients with sarcoma.

Study Overview

• Status: Completed
• Conditions: Sarcoma; Ovarian Cancer
• Intervention / Treatment: Drug: cyclophosphamide; Radiation: radiation therapy; Procedure: therapeutic conventional surgery; Drug: etoposide; Drug: vincristine sulfate; Procedure: adjuvant therapy; Procedure: neoadjuvant therapy; Drug: doxorubicin hydrochloride; Radiation: brachytherapy; Drug: ifosfamide; Radiation: intraoperative radiation therapy

Detailed Description

OBJECTIVES:

• To evaluate the efficacy, in terms of clinical response, pathologic response, and long-term disease-free survival, of a multidrug chemotherapy regimen patients with spindle cell or small round cell sarcoma.

OUTLINE: This is a multicenter study.

• Induction therapy: Patients receive vincristine IV, cyclophosphamide IV over 1 hour and doxorubicin hydrochloride IV over 48 hours on day 1 in week 0. Patients continue to receive vincristine IV once weekly in weeks 1 and 2. Patients also receive etoposide IV over 1 hour and ifosfamide IV over 1 hour for 5 days in week 3. Treatment repeats every 6 weeks for 2 courses.
• Local control: After completing induction therapy, patients are reevaluated for local control therapy. Some patients may undergo surgery and/or radiotherapy (e.g., brachytherapy, intraoperative radiotherapy, external beam therapy). Patients who undergo surgery begin consolidation therapy 2 weeks after completing surgery. Some patients undergo radiotherapy 5 days a week for 5½ weeks beginning at week 12 and/or after surgery (weeks 15-16).
• Consolidation therapy: Patients receive vincristine IV, doxorubicin hydrochloride IV over 1 hour, and cyclophosphamide IV over 1 hour once in weeks 12 and 18*. Patients also receive etoposide IV over 1 hour and ifosfamide IV over 1 hour for 5 days in week 15. Patients are reevaluated for local control therapy at week 21.

NOTE: *Patients undergoing radiotherapy do not receive doxorubicin hydrochloride in week 18 or week 24.

• Maintenance therapy: Patient receive vincristine IV, doxorubicin hydrochloride IV over 1 hour, and cyclophosphamide IV over 1 hour once in week 24. Patients also receive etoposide IV over 1 hour and ifosfamide IV over 1 hour for 5 days in week 21. Treatment repeats every 6 weeks for 3 courses. In week 36, patients receive vincristine, doxorubicin hydrochloride and cyclophosphamide OR etoposide and ifosfamide as before. In week 39 patients receive etoposide and ifosfamide as before.

After completion of treatment, patients are followed periodically for at least 5 years.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 21 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Diagnosis of any of the following:

  • High-grade nonmetastatic, nonrhabdomyosarcomatous soft tissue sarcomas (excluding undifferentiated sarcoma and Ewing sarcoma)
  • Small round cell sarcomas (excluding primitive neuroectodermal tumors of soft tissue) (closed to accrual)
  • Undifferentiated sarcomas (closed to accrual)
  • Rhabdomyosarcomas (excluding non-parameningeal head tumors, vaginal or stage I paratesticular) (closed to accrual)
  • All alveolar rhabdomyosarcomas (closed to accrual)

• No evidence distant metastatic disease (i.e., lung, bone, bone marrow)

  • Local or regional nodal disease allowed
• No spindle cell tumors of bone
• Primary lesions do not have to be resectable

PATIENT CHARACTERISTICS:

• Creatinine ≤1.5 mg/dL OR creatinine clearance > 60 mL/min/
• AST/ALT < 2 times upper limit of normal (ULN)
• Total bilirubin < 2 times ULN
• LVEF ≥ 45%
• No prior history of cancer
• Not pregnant or nursing
• Negative pregnancy test

PRIOR CONCURRENT THERAPY:

• Patients who have undergone radiation therapy after initial surgery are eligible but must have evaluation for metastatic disease within 2 weeks of starting chemotherapy
• No prior chemotherapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Efficacy in terms of long-term disease-free survival
Clinical response of the tumors
Pathologic response of the tumors
Long term disease-free survival

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Carola A. S. Arndt, MD, Mayo Clinic

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 1, 1991
• Primary Completion (ACTUAL): October 21, 2013
• Study Completion (ACTUAL): October 21, 2013

Study Registration Dates

• First Submitted: April 18, 2008
• First Submitted That Met QC Criteria: April 18, 2008
• First Posted (ESTIMATE): April 21, 2008

Study Record Updates

• Last Update Posted (ACTUAL): October 9, 2018
• Last Update Submitted That Met QC Criteria: October 4, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: previously treated childhood rhabdomyosarcoma; recurrent childhood rhabdomyosarcoma; ovarian sarcoma; stage II uterine sarcoma; stage III uterine sarcoma; recurrent childhood soft tissue sarcoma; alveolar childhood rhabdomyosarcoma; embryonal childhood rhabdomyosarcoma; previously untreated childhood rhabdomyosarcoma; nonmetastatic childhood soft tissue sarcoma; childhood desmoplastic small round cell tumor
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Cyclophosphamide; Etoposide; Ifosfamide; Doxorubicin; Liposomal doxorubicin; Vincristine
• Other Study ID Numbers: CDR0000582271; P30CA015083 (U.S. NIH Grant/Contract); 919110 (OTHER: Mayo Clinic Cancer Center); 542-91 (OTHER: Mayo Clinic IRB); 0791 (REGISTRY: COGUM)