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

Sarcoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00544778
• Other study ID #: 00050
• Secondary ID: P30CA033572CHNMC
• Status: Terminated
• Phase: Phase 2
• First received: October 13, 2007
• Last updated: August 19, 2014
• Start date: August 2001

Study information

• Verified date: August 2014
• Source: City of Hope Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 7
• Est. primary completion date: November 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Osteosarcoma
• Sarcoma

Intervention

Biological:
• filgrastim

Drug:
• dexrazoxane hydrochloride

• doxorubicin hydrochloride

• ifosfamide

• irinotecan hydrochloride

Genetic:
• protein expression analysis

Other:
• immunoenzyme technique

Procedure:
• adjuvant therapy

• conventional surgery

• neoadjuvant therapy

Radiation:
• radiation therapy

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
City of Hope Medical Center	National Cancer Institute (NCI)

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response Rate	Response rate defined as the proportion of subjects with confirmed partial or complete response as defined by the RECIST criteria.	First disease evaluation one month after the start of treatment and every 3 months there after, up to 2 years.	No