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

Sponsor:	Beckman Research Institute
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00544778

Purpose

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.

Condition	Intervention	Phase
Sarcoma	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	Phase II

Study Type:	Interventional
Study Design:	Treatment
Official Title:	Phase II Trial of Neoadjuvant Dose-Dense Doxorubicin, Ifosfamide, and Irinotecan (CPT-11) for Advanced Soft Tissue and Recurrent Bone Sarcomas

Resource links provided by NLM:

MedlinePlus related topics: Cancer Soft Tissue Sarcoma Surgery

Drug Information available for: ICRF 159 Razoxane Doxorubicin Dexrazoxane Doxorubicin hydrochloride Irinotecan U 101440E Myocet Filgrastim Irinotecan hydrochloride Dexrazoxane hydrochloride Ifosfamide

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Response rate [ Designated as safety issue: No ]

Secondary Outcome Measures:

Toxicity [ Designated as safety issue: Yes ]
Overall survival [ Designated as safety issue: No ]
Disease-free survival [ Designated as safety issue: No ]

Estimated Enrollment:	44
Study Start Date:	August 2001

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.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00544778

Sponsors and Collaborators

Beckman Research Institute

National Cancer Institute (NCI)

Investigators

Study Chair:

Warren A. Chow, MD

Beckman Research Institute

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000566381, CHNMC-00050
Study First Received:	October 13, 2007
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00544778 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

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

Additional relevant MeSH terms:

Neuroectodermal Tumors, Primitive
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Neoplasms, Nerve Tissue
Irinotecan
Antibiotics, Antineoplastic
Razoxane
Neoplasms, Connective and Soft Tissue
Neoplasms, Germ Cell and Embryonal
Therapeutic Uses
Alkylating Agents
Neoplasms by Histologic Type
Enzyme Inhibitors
Cardiovascular Agents

Doxorubicin
Camptothecin
Pharmacologic Actions
Neuroectodermal Tumors
Neoplasms
Ifosfamide
Sarcoma
Chelating Agents
Antineoplastic Agents, Alkylating
Neoplasms, Neuroepithelial
Antineoplastic Agents, Phytogenic
Neuroectodermal Tumors, Primitive, Peripheral
Isophosphamide mustard
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on November 22, 2009