Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Closed 15-75 Pharmaceutical / Industry EORTC-62951

Objectives

I.  Determine complete and partial response rates and duration of response of 
raltitrexed (Tomudex) in patients with recurrent metastatic soft tissue 
sarcoma.

II.  Characterize the acute side effects of raltitrexed in patients with 
recurrent metastatic soft tissue sarcoma.

Entry Criteria

Disease Characteristics:

Histologically confirmed recurrent metastatic soft tissue sarcoma
Following cell types are included:
 - Malignant fibrous histiocytoma
 - Liposarcoma
 - Rhabdomyosarcoma
 - Synovial sarcoma
 - Malignant paraganglioma
 - Fibrosarcoma
 - Leiomyosarcoma
 - Angiosarcoma including hemangiopericytoma
 - Neurogenic sarcoma
 - Unclassified sarcoma
 - Miscellaneous sarcoma including mixed mesodermal tumors of the uterus

Excluding the following cell types:  malignant mesothelioma, chondrosarcoma,
neuroblastoma, osteosarcoma, Ewing's sarcoma, and embryonal rhabdomyosarcoma

Must have measurable lesion with evidence of progression within 6 weeks prior
to treatment
 Specific minimum criteria for measurability are:
  - lung metastases greater than 2.0 cm in diameter
  - superficial lymph nodes greater than 2.5 cm in diameter
  - skin and subcutaneous metastases greater than 2.5 cm in diameter
  - lymph node metastases in the mediastinum and in the retroperitoneal region
    greater than 2.5 cm in diameter as measured by CT scan
  - liver metastases greater than 2.5 cm in diameter as measured by ultrasound
    or CT scan

Osseous lesions, hepatomegaly, lymphedema, ascites, and pleural effusions are
not accepted as solitary tumor response parameters, because they cannot be
measured 

Must have previously received only 1 line of previous combination chemotherapy
either as an adjuvant or for metastatic disease or 2 single agents regimens
either as adjuvants or for metastatic disease

No symptomatic or known CNS metastases

Prior/Concurrent Therapy:

Biologic therapy:
 No concurrent biologic therapy

Chemotherapy:
 See Disease Characteristics
 Only 1 prior combination chemotherapy regimen allowed OR
 Only 2 prior single agent chemotherapy regimens allowed
 At least 6 weeks since nitrosoureas or mitomycin
 At least 4 weeks since other chemotherapy
 No concurrent systemic chemotherapy

Endocrine therapy:
 No concurrent endocrine therapy

Radiotherapy:
 No prior radiotherapy to the sole index lesion available

Surgery:
 Not specified

Other:
 No concurrent vitamin supplement containing folic acid

Patient Characteristics:

Age:
 15 to 75

Performance status:
 WHO 0-2

Life expectancy:
 Not specified

Hematopoietic:
 WBC at least 4,000/mm3
 Platelet count at least 100,000/mm3

Hepatic:
 Albumin at least 25 g/L
 Bilirubin no greater than 30 micromole/L

Renal:
 Creatinine no greater than 120 micromole/L OR
 Creatinine clearance at least 65 mL/min

Cardiovascular:
 No history of cardiovascular disease

Other:
 No secondary primary malignant tumor except basal cell carcinoma or
  adequately treated in situ carcinoma of cervix 
 No other severe medical illness, including psychosis 
 Adequate contraception required of all fertile patients

Expected Enrollment

There will be 33 patients accrued into this study with 22 patients for the 
first stage of study.

Outline

This is a multicenter, open label, nonrandomized study.

Raltitrexed is administered as a 15 minute IV infusion every 3 weeks.  
Treatment should be given for at least 2 cycles unless there is rapid 
progression of disease.  In the case of complete response (CR), two more 
cycles are administered.  Treatment is continued for partial response or 
stable disease until progression of disease or unacceptable toxicity.  

If among the first 22 patients accrued there are no more than 2 responding 
patients, study treatment is stopped.  If more than 2 patients respond to 
treatment, accrual is continued until 33 patients are evaluable for response.

The disease is assessed every 6 weeks, during and after treatment, until 
documented progression of disease at which time patients are followed every 12 
weeks. 

Trial Contact Information

Trial Lead Organizations

European Organization for Research and Treatment of Cancer

Jean-Yves Blay, MD, PhD, Protocol chair		Ph: 33-78-782-828 Email: blay@lyon.fnclcc.fr