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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

This study has been terminated.
(The study was terminated prematurely due to withdrawal of support by the sponsor.)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT00544778
First received: October 13, 2007
Last updated: August 19, 2014
Last verified: August 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: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
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 [ Time Frame: First disease evaluation one month after the start of treatment and every 3 months there after, up to 2 years. ] [ Designated as safety issue: No ]
    Response rate defined as the proportion of subjects with confirmed partial or complete response as defined by the RECIST criteria.


Enrollment: 7
Study Start Date: August 2001
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
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.
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

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Results First Received: June 12, 2014
Last Updated: August 19, 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
Sarcoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Dexrazoxane
Doxorubicin
Ifosfamide
Irinotecan
Isophosphamide mustard
Liposomal doxorubicin
Razoxane
Alkylating Agents
Antibiotics, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Phytogenic
Cardiotonic Agents
Cardiovascular Agents
Enzyme Inhibitors
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014