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

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC (Other)

Overall Status

Completed

CT.gov ID

NCT00030784

Collaborator

(none)

Enrollment

Locations

Patients Per Site

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Sarcoma	Drug: ifosfamide Drug: pegylated liposomal doxorubicin hydrochloride	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

28 participants

Primary Purpose:

Treatment

Official Title:

Phase I Study To Determine The Safety Of Caelyx (Doxorubin HCI, Pegylated Liposomal) In Combination With Ifosfamide In Previously Untreated Adult Patients With Advanced And/Or Metastatic Soft Tissues Sarcomas

Study Start Date :

Nov 1, 2001

Actual Primary Completion Date :

Mar 1, 2005

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Aarhus University Hospital - Aarhus Sygehus - Norrebrogade	Aarhus		Denmark	DK-8000
2	Robert Roessle Comprehensive Cancer Center at University of Berlin - Charite Campus Buch	Berlin		Germany	D-13122