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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT00544778
First received: October 13, 2007
Last updated: March 27, 2014
Last verified: March 2014
  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 2

Study Type: Interventional
Study Design: Primary Purpose: 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:


Further study details as provided by City of Hope Medical Center:

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 ]

Enrollment: 7
Study Start Date: August 2001
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
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
City of Hope Medical Center
Investigators
Study Chair: Warren A. Chow, MD Beckman Research Institute
  More Information

Additional Information:
No publications provided

Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT00544778     History of Changes
Other Study ID Numbers: 00050, P30CA033572, CHNMC-00050, CDR0000566381
Study First Received: October 13, 2007
Last Updated: March 27, 2014
Health Authority: United States: Federal Government

Keywords provided by City of Hope Medical Center:
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:
Osteosarcoma
Neuroectodermal Tumors, Primitive, Peripheral
Sarcoma
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Doxorubicin
Isophosphamide mustard
Irinotecan
Ifosfamide
Razoxane
Camptothecin
Lenograstim
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Chelating Agents

ClinicalTrials.gov processed this record on April 22, 2014