Combination Chemotherapy and Dexrazoxane Followed by Surgery and Radiation Therapy in Treating Patients With Advanced Soft Tissue Sarcoma or Recurrent Bone Sarcoma

Phase 2

Terminated

• Conditions: Sarcoma
• Interventions: Biological: filgrastim; Drug: dexrazoxane hydrochloride; Drug: doxorubicin hydrochloride; Drug: ifosfamide; Drug: irinotecan hydrochloride; Genetic: protein expression analysis; Other: immunoenzyme technique; Procedure: adjuvant therapy; Procedure: conventional surgery; Procedure: neoadjuvant therapy; Radiation: radiation therapy

• Registration Number: NCT00544778
• Lead Sponsor: City of Hope Medical Center

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as doxorubicin, ifosfamide, and irinotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Chemoprotective drugs, such as dexrazoxane, may protect normal cells from the side effects of chemotherapy. Giving combination chemotherapy together with dexrazoxane before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving radiation therapy after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with dexrazoxane followed by surgery and radiation therapy works in treating patients with advanced soft tissue sarcoma or recurrent bone sarcoma.

Detailed Description

OBJECTIVES:

* To evaluate the effectiveness of neoadjuvant dose-dense chemotherapy comprising doxorubicin hydrochloride, ifosfamide, and irinotecan hydrochloride in combination with dexrazoxane hydrochloride followed by surgery and radiotherapy in patients with advanced soft tissue sarcoma or recurrent bone sarcoma.

* To evaluate the toxicities of this regimen in these patients.

* To compare the duration of disease-free and overall survival of patients with advanced soft tissue sarcoma who receive this therapy on a neoadjuvant basis with historical controls.

* To evaluate laboratory correlates of chemotherapy resistance for the cytotoxic agents used in this study.

OUTLINE: Patients are stratified by type of sarcoma (soft tissue vs bone), prior treatment (untreated vs treated), and presence of metastases (yes vs no).

* Courses 1 and 2: Patients receive doxorubicin hydrochloride and dexrazoxane hydrochloride IV continuously over 96 hours. Treatment repeats every 3 weeks for 2 courses.

* Courses 3 and 4: Patients receive ifosfamide IV over 2 hours twice a day (every 12 hours) on days 1-3. Treatment repeats every 3 weeks for 2 courses.

* Courses 5 and 6: Patients receive irinotecan hydrochloride IV over 1 hour once a day on days 1-5 and 8-12. Treatment repeats every 3 weeks for 2 courses.

Patients also receive filgrastim (G-CSF) subcutaneously once a day beginning 3 days after completion of chemotherapy and continuing until blood counts recover.

Patients then undergo standard surgery and radiotherapy.

Patients undergo blood sample collection periodically for correlative studies. Samples are analyzed for MDR (multidrug resistance gene) protein expression via immunoperoxidase staining.

After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 2 years, and then once a year thereafter.

Study Timeline

• Study Start: 2001-08
• Study First Submitted: 2007-10-13
• Study First Submitted QC: 2007-10-13
• Study First Posted: 2007-10-16
• Primary Completion: 2011-11
• Results First Submitted: 2014-06-12
• Status Verified: 2014-08
• Results First Submitted QC: 2014-08-19
• Last Update Submitted: 2014-08-19
• Results First Posted: 2014-08-28
• Last Update Posted: 2014-08-28

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 7

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm 1	radiation therapy	High-dose chemotherapy with doxorubicin at 120 mg/m2 and ifosfamide at 2 g/m2 followed by a prolonged schedule of CPT-11 at 20 mg/m2.
Arm 1	dexrazoxane hydrochloride	High-dose chemotherapy with doxorubicin at 120 mg/m2 and ifosfamide at 2 g/m2 followed by a prolonged schedule of CPT-11 at 20 mg/m2.
Arm 1	ifosfamide	High-dose chemotherapy with doxorubicin at 120 mg/m2 and ifosfamide at 2 g/m2 followed by a prolonged schedule of CPT-11 at 20 mg/m2.
Arm 1	adjuvant therapy	High-dose chemotherapy with doxorubicin at 120 mg/m2 and ifosfamide at 2 g/m2 followed by a prolonged schedule of CPT-11 at 20 mg/m2.
Arm 1	neoadjuvant therapy	High-dose chemotherapy with doxorubicin at 120 mg/m2 and ifosfamide at 2 g/m2 followed by a prolonged schedule of CPT-11 at 20 mg/m2.
Arm 1	protein expression analysis	High-dose chemotherapy with doxorubicin at 120 mg/m2 and ifosfamide at 2 g/m2 followed by a prolonged schedule of CPT-11 at 20 mg/m2.
Arm 1	immunoenzyme technique	High-dose chemotherapy with doxorubicin at 120 mg/m2 and ifosfamide at 2 g/m2 followed by a prolonged schedule of CPT-11 at 20 mg/m2.
Arm 1	conventional surgery	High-dose chemotherapy with doxorubicin at 120 mg/m2 and ifosfamide at 2 g/m2 followed by a prolonged schedule of CPT-11 at 20 mg/m2.
Arm 1	filgrastim	High-dose chemotherapy with doxorubicin at 120 mg/m2 and ifosfamide at 2 g/m2 followed by a prolonged schedule of CPT-11 at 20 mg/m2.
Arm 1	doxorubicin hydrochloride	High-dose chemotherapy with doxorubicin at 120 mg/m2 and ifosfamide at 2 g/m2 followed by a prolonged schedule of CPT-11 at 20 mg/m2.
Arm 1	irinotecan hydrochloride	High-dose chemotherapy with doxorubicin at 120 mg/m2 and ifosfamide at 2 g/m2 followed by a prolonged schedule of CPT-11 at 20 mg/m2.

Primary Outcome Measures

Name	Time	Method
Response Rate	First disease evaluation one month after the start of treatment and every 3 months there after, up to 2 years.	Response rate defined as the proportion of subjects with confirmed partial or complete response as defined by the RECIST criteria.