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

Primary Purpose

Sarcoma

Status

Terminated

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

filgrastim

dexrazoxane hydrochloride

doxorubicin hydrochloride

ifosfamide

irinotecan hydrochloride

protein expression analysis

immunoenzyme technique

adjuvant therapy

conventional surgery

neoadjuvant therapy

radiation therapy

About this trial

This is an interventional treatment trial for Sarcoma focused on measuring recurrent adult soft tissue sarcoma, stage III adult soft tissue sarcoma, stage IV adult soft tissue sarcoma, metastatic osteosarcoma, recurrent osteosarcoma, metastatic Ewing sarcoma/peripheral primitive neuroectodermal tumor, recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor, Ewing sarcoma of bone

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS:

Diagnosis of 1 of the following:
- Primary soft tissue sarcoma at high-risk* for recurrence, meeting any of the following criteria:
  - Previously untreated locally advanced, nonmetastatic disease
  - Advanced (metastatic) disease not amenable to standard or higher priority investigational neoadjuvant therapies
- Recurrent bone sarcoma (e.g., osteogenic sarcoma, Ewing sarcoma, or peripheral neuroectodermal tumor)
  - Must have advanced locally recurrent or metastatic disease NOTE: *High-risk is defined as high-grade, deep to fascia, and > 5 cm in greatest dimension
Measurable or nonmeasurable disease is not required
Pre-chemotherapy consultation with surgery and radiation oncology is required for formulation of loco-regional therapy
No gastrointestinal stromal cell sarcoma
No alveolar soft part sarcoma
No symptomatic brain metastases
- No requirement for anticonvulsant or corticosteroid therapy

PATIENT CHARACTERISTICS:

Karnofsky performance status 70-100%
Life expectancy ≥ 2 months
Absolute neutrophil count ≥ 2,000/mm^3
Platelet count > 120,000/mm^3
Creatinine clearance > 50 mL/min
Serum bilirubin ≤ 1.5 mg/dL
SGOT or SGPT ≤ 2.5 times upper limit of normal
Serum albumin ≥ 2.5 mg/dL
LVEF ≥ 50% by MUGA scan
Not pregnant or nursing
Fertile patients must use effective contraception
No concurrent nonmalignant illness (e.g., cardiovascular, pulmonary, or CNS disease) that is poorly controlled with currently available treatment or is of such severity that the investigators deem it unwise for the patient to enter the study

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
No prior chemotherapy for recurrent (local or metastatic) soft tissue sarcoma
Prior chemotherapy for recurrent bone sarcoma allowed provided the total dose of doxorubicin hydrochloride is ≤ 300 mg/m^2
No prior radiotherapy to > 25% of bone marrow
At least 3 weeks since prior radiotherapy or chemotherapy

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm 1

Arm Description

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.

Outcomes

Primary Outcome Measures

Response Rate

Response rate defined as the proportion of subjects with confirmed partial or complete response as defined by the RECIST criteria.

Secondary Outcome Measures

Full Information

NCT ID

NCT00544778

First Posted

October 13, 2007

Last Updated

August 19, 2014

Sponsor

City of Hope Medical Center

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT00544778

Brief Title

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

Official Title

Phase II Trial of Neoadjuvant Dose-Dense Doxorubicin, Ifosfamide, and Irinotecan (CPT-11) for Advanced Soft Tissue and Recurrent Bone Sarcomas

Study Type

Interventional

2. Study Status

Record Verification Date

August 2014

Overall Recruitment Status

Terminated

Why Stopped

The study was terminated prematurely due to withdrawal of support by the sponsor.

Study Start Date

August 2001 (undefined)

Primary Completion Date

November 2011 (Actual)

Study Completion Date

undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

City of Hope Medical Center

Collaborators

National Cancer Institute (NCI)

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Sarcoma

Keywords

recurrent adult soft tissue sarcoma, stage III adult soft tissue sarcoma, stage IV adult soft tissue sarcoma, metastatic osteosarcoma, recurrent osteosarcoma, metastatic Ewing sarcoma/peripheral primitive neuroectodermal tumor, recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor, Ewing sarcoma of bone

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

7 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm 1

Arm Type

Experimental

Arm Description

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.

Intervention Type

Biological

Intervention Name(s)

filgrastim

Intervention Type

Drug

Intervention Name(s)

dexrazoxane hydrochloride

Intervention Type

Drug

Intervention Name(s)

doxorubicin hydrochloride

Intervention Type

Drug

Intervention Name(s)

ifosfamide

Intervention Type

Drug

Intervention Name(s)

irinotecan hydrochloride

Intervention Type

Genetic

Intervention Name(s)

protein expression analysis

Intervention Type

Other

Intervention Name(s)

immunoenzyme technique

Intervention Type

Procedure

Intervention Name(s)

adjuvant therapy

Intervention Type

Procedure

Intervention Name(s)

conventional surgery

Intervention Type

Procedure

Intervention Name(s)

neoadjuvant therapy

Intervention Type

Radiation

Intervention Name(s)

radiation therapy

Primary Outcome Measure Information:

Title

Response Rate

Description

Response rate defined as the proportion of subjects with confirmed partial or complete response as defined by the RECIST criteria.

Time Frame

First disease evaluation one month after the start of treatment and every 3 months there after, up to 2 years.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

DISEASE CHARACTERISTICS: Diagnosis of 1 of the following: Primary soft tissue sarcoma at high-risk* for recurrence, meeting any of the following criteria: Previously untreated locally advanced, nonmetastatic disease Advanced (metastatic) disease not amenable to standard or higher priority investigational neoadjuvant therapies Recurrent bone sarcoma (e.g., osteogenic sarcoma, Ewing sarcoma, or peripheral neuroectodermal tumor) Must have advanced locally recurrent or metastatic disease NOTE: *High-risk is defined as high-grade, deep to fascia, and > 5 cm in greatest dimension Measurable or nonmeasurable disease is not required Pre-chemotherapy consultation with surgery and radiation oncology is required for formulation of loco-regional therapy No gastrointestinal stromal cell sarcoma No alveolar soft part sarcoma No symptomatic brain metastases No requirement for anticonvulsant or corticosteroid therapy PATIENT CHARACTERISTICS: Karnofsky performance status 70-100% Life expectancy ≥ 2 months Absolute neutrophil count ≥ 2,000/mm^3 Platelet count > 120,000/mm^3 Creatinine clearance > 50 mL/min Serum bilirubin ≤ 1.5 mg/dL SGOT or SGPT ≤ 2.5 times upper limit of normal Serum albumin ≥ 2.5 mg/dL LVEF ≥ 50% by MUGA scan Not pregnant or nursing Fertile patients must use effective contraception No concurrent nonmalignant illness (e.g., cardiovascular, pulmonary, or CNS disease) that is poorly controlled with currently available treatment or is of such severity that the investigators deem it unwise for the patient to enter the study PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior chemotherapy for recurrent (local or metastatic) soft tissue sarcoma Prior chemotherapy for recurrent bone sarcoma allowed provided the total dose of doxorubicin hydrochloride is ≤ 300 mg/m^2 No prior radiotherapy to > 25% of bone marrow At least 3 weeks since prior radiotherapy or chemotherapy

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Warren A. Chow, MD

Organizational Affiliation

City of Hope Comprehensive Cancer Center

Official's Role

Study Chair

12. IPD Sharing Statement

Learn more about this trial

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

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