RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase II trial to study the effectiveness of brostallicin in treating patients who have locally advanced or metastatic soft tissue sarcoma that has not responded to one previous chemotherapy regimen.

Condition	Treatment or Intervention	Phase
adult soft tissue sarcoma gastrointestinal stromal tumor	Drug: brostallicin  Procedure: chemotherapy	Phase II

Further Study Details: 

OBJECTIVES:

• Determine the antitumor activity of brostallicin, in terms of objective response, in patients with locally advanced or metastatic soft tissue sarcoma who have failed one prior chemotherapy treatment.
• Determine the time to progression and duration of response in patients treated with this drug.
• Determine the safety and toxic effects of this drug in these patients.
• Correlate clinical outcome with whole blood glutathione level in patients treated with this drug.

OUTLINE: This is a multicenter study. Patients are stratified according to tumor (tumors other than gastrointestinal stromal tumor (GIST) vs GIST).

Patients receive brostallicin IV over 10 minutes on day 1. Treatment repeats every 21 days for at least 4 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 2 months for 1 year and then every 4 months for 1 year.

PROJECTED ACCRUAL: A total of 58-72 patients (40 for stratum I and 18-32 for stratum II) will be accrued for this study.

Ages Eligible for Study:  15 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed soft tissue sarcoma that is not amenable to surgery, radiotherapy, or combined modality therapy with curative intent
• Stratum I
• Malignant fibrous histiocytoma
• Liposarcoma
• Rhabdomyosarcoma
• Synovial sarcoma
• Malignant paraganglioma
• Fibrosarcoma
• Leiomyosarcoma
• Angiosarcoma including hemangiopericytoma
• Malignant peripheral nerve sheath tumor
• Unclassified sarcoma
• Miscellaneous sarcoma
• Stratum II
• Gastrointestinal stromal tumor
• Previously treated with imatinib mesylate for locally advanced or metastatic disease and demonstrated disease progression
• The following sarcoma types are excluded:
• Mixed mesodermal tumors of the uterus (and carcinosarcoma)
• Chondrosarcoma
• Malignant mesothelioma
• Neuroblastoma
• Osteosarcoma
• Ewing's sarcoma
• Embryonal rhabdomyosarcoma
• At least one measurable lesion
• Progressive disease after 1 prior anthracycline- and/or alkylating-containing chemotherapy regimen for locally advanced or metastatic disease
• Clinical evidence of progression within 6 weeks prior to study treatment
• No known or symptomatic CNS metastases

PATIENT CHARACTERISTICS: Age:

• Over 15

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 1.25 times upper limit of normal (ULN)
• SGPT and SGOT no greater than 3 times ULN
• Alkaline phosphatase no greater than 2.5 times ULN

Renal:

• Creatinine no greater than 1.4 mg/dL OR
• Creatinine clearance greater than 65 mL/min

Cardiovascular:

• No prior severe cardiovascular disease

Other:

• Not pregnant
• Negative pregnancy test
• Fertile patients must use effective contraception during and for up to 6 months after study
• No other prior or concurrent malignancy except adequately treated basal cell skin cancer or carcinoma in situ of the cervix
• No other severe medical illness
• No psychosis

PRIOR CONCURRENT THERAPY: Biologic therapy:

• No concurrent biologic response modifiers or immunotherapy
• No concurrent prophylactic hematopoietic growth factors (e.g., filgrastim (G- CSF) or sargramostim (GM-CSF)

Chemotherapy:

• See Disease Characteristics
• More than 4 weeks since prior chemotherapy and recovered
• Prior adjuvant chemotherapy as first-line treatment allowed provided disease progressed within 6 months after the completion of chemotherapy
• No prior ecteinascidin 743 (stratum I)
• No other concurrent chemotherapy

Endocrine therapy:

• No concurrent hormonal therapy

Radiotherapy:

• See Disease Characteristics
• Recovered from prior radiotherapy
• No prior radiotherapy to sole measurable lesion
• Concurrent palliative radiotherapy to nontarget lesions allowed at investigator's discretion

Surgery:

• See Disease Characteristics
• Recovered from prior surgery

Other:

• No other concurrent anticancer therapy (approved or investigational)
• No concurrent participation in any other clinical treatment study
• No other concurrent investigational drugs

Belgium
      U.Z. Gasthuisberg, Leuven,  B-3000,  Belgium
      Universitair Ziekenhuis Antwerpen, Edegem,  B-2650,  Belgium
France
      Centre Leon Berard, Lyon,  69008,  France
      CHU de la Timone, Marseille,  13385,  France
      Institut Gustave Roussy, Villejuif,  F-94805,  France
Germany
      Klinikum Grosshadern der Ludwig-Maximilians Universitaet Muenchen, Munich,  D-81377,  Germany
      Medizinische Hochschule Hannover, Hannover,  D-30625,  Germany
      Robert Roessle Klinik, Berlin,  D-13122,  Germany
      Universitaets-Krankenhaus Eppendorf, Hamburg,  D-20246,  Germany
Netherlands
      Academisch Ziekenhuis Groningen, Groningen,  9700 RB,  Netherlands
      Daniel Den Hoed Cancer Center at Erasmus University Medical Center, Rotterdam,  3008 AE,  Netherlands
      Leiden University Medical Center, Leiden,  2300 RC,  Netherlands
      Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam,  1066 CX,  Netherlands
United Kingdom, England
      Northern Centre for Cancer Treatment at Newcastle General Hospital, Newcastle upon Tyne,  England,  NE4 6BE,  United Kingdom
      Royal Marsden NHS Trust - London, London,  England,  SW3 6JJ,  United Kingdom
      St. James's University Hospital, Leeds,  England,  LS9 7TF,  United Kingdom

Study chairs or principal investigators

Michael Leahy, MBChB, FRACP, FRCP, FRC PATH,  Fremantle Hospital   

Study ID Numbers:  CDR0000069456; EORTC-62011
Record last reviewed:  March 2004
Last Updated:  October 13, 2004
Record first received:  July 8, 2002
ClinicalTrials.gov Identifier:  NCT00041249
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08