Patient case: 78-year-old female with sarcoma; genetic feature: MDM2

Clinical trial: Liposomal Doxorubicin Plus Ifosfamide in Treating Patients With Advanced or Metastatic Soft Tissue Sarcoma

Summary: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.
  PURPOSE: Phase I trial to study the effectiveness of combining liposomal doxorubicin with ifosfamide in treating patients who have advanced or metastatic soft tissue sarcoma.

Detailed description: OBJECTIVES:
  -  Determine the maximum tolerated dose of ifosfamide in combination with doxorubicin HCl liposome in patients with previously untreated advanced or metastatic soft tissue sarcoma.
  -  Determine the objective response in patients treated with this regimen.
  -  Determine the dose-limiting toxicity in patients treated with this regimen.
  OUTLINE: This is a multicenter, dose-escalation study of ifosfamide.
  Patients receive doxorubicin HCl liposome IV over 1 hour on day 1 and ifosfamide IV over 4 hours on days 1-3 OR on days 1-4 (for patients enrolled on dose level 6). Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
  Cohorts of 3-6 patients receive escalating doses of ifosfamide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
  Patients are followed every 8 weeks until disease progression and then every 12 weeks thereafter.
  PROJECTED ACCRUAL: A total of 3-24 patients will be accrued for this study.

Eligibility: DISEASE CHARACTERISTICS:
  -  Histologically confirmed soft tissue sarcoma
  -  Advanced and/or metastatic disease
  -  Must be of any of the following types:
  -  Malignant fibrous histiocytoma
  -  Liposarcoma (excluding lipomas and well-differentiated liposarcomas)
  -  Rhabdomyosarcoma
  -  Synovial sarcoma
  -  Malignant paraganglioma
  -  Fibrosarcoma
  -  Leiomyosarcoma
  -  Angiosarcoma
  -  Neurogenic sarcoma
  -  Sarcoma not otherwise specified
  -  Paraffin blocks and slides must be available
  -  Measurable disease
  -  Osseous lesions and pleural effusions are not considered measurable disease
  -  Evidence of progressive disease within the past 6 weeks
  -  The following conditions are excluded:
  -  Gastrointestinal stromal tumors
  -  Malignant mesothelioma
  -  Chondrosarcoma
  -  Neuroblastoma
  -  Osteosarcoma
  -  Ewing's sarcoma
  -  Embryonal rhabdomyosarcoma
  -  No symptomatic or known CNS metastases
  PATIENT CHARACTERISTICS:
  Age:
  -  18 to 70
  Performance status:
  -  WHO 0-1
  Life expectancy:
  -  Not specified
  Hematopoietic:
  -  WBC at least 4,000/mm^3
  -  Platelet count at least 100,000/mm^3
  Hepatic:
  -  Bilirubin no greater than 1.75 mg/dL
  -  Albumin at least 2.5 g/dL
  Renal:
  -  Creatinine no greater than 1.4 mg/dL
  -  Creatinine clearance at least 65 mL/min
  Cardiovascular:
  -  Ejection fraction at least 50% by echocardiogram or isotopic methods
  -  No history of cardiovascular disease
  Other:
  -  No other prior or concurrent primary malignancies except adequately treated carcinoma in situ of the cervix or basal cell carcinoma
  -  No other severe medical illness
  -  No psychosis
  -  No psychological, familial, sociological, or geographical condition that would preclude study participation
  -  Not pregnant
  -  Fertile patients must use effective contraception (barrier method for men) during and for 6 months after study participation
  PRIOR CONCURRENT THERAPY:
  Biologic therapy:
  -  Not specified
  Chemotherapy:
  -  No prior chemotherapy for advanced disease
  -  No other concurrent systemic chemotherapy for malignancy
  Endocrine therapy:
  -  Not specified
  Radiotherapy:
  -  No prior radiotherapy to sole indicator lesion
  -  Concurrent radiotherapy allowed except to sole indicator lesion
  Surgery:
  -  Not specified
  Other:
  -  No other concurrent investigational drugs

Relevance to patient case: not relevant