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

European Organisation for Research and Treatment of Cancer (EORTC)

Status and phase

Completed

Phase 1

Conditions

Sarcoma

Treatments

Drug: pegylated liposomal doxorubicin hydrochloride

Drug: ifosfamide

Study type

Interventional

Funder types

NETWORK

Identifiers

NCT00030784

EORTC-62002

Details and patient eligibility

About

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.

Full 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.

Enrollment

28 patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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: