Trofosfamide Versus Adriamycin in Elderly Patients With Soft Tissue Sarcoma (STS)

Study Overview
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Brief Summary
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The goal of this trial is to determine whether oral continuous (metronomic) therapy with trofosfamide results in a similar rate of progression-free time after 6 months as intravenous treatment with adriamycin. In addition, the study is intended to investigate the level of toxicity associated with the two treatment regimens (safety profile).

Detailed Description
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Group A:Adriamycin (60 mg/m2, d1, qd22) 75 mg/m2 may be applied instead of 60 mg/m2 for patients between 60 and 70 years of age (optional) Group B:Trofosfamide (300 mg absolute p.o. qd over 7 days, then 150 mg p.o. absolute qd continuously) In case of absence of any toxicity during treatment with trofosfamide 150 mg absolute a dose escalation to 200 mg absolute is allowed (optional)

Official Title
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Randomized Phase II Trial of Trofosfamide vs. Adriamycin in Elderly Patients With Previously Untreated Metastatic Soft Tissue Sarcoma

Conditions
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Sarcoma, Soft Tissue

Intervention / Treatment
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* Drug: Adriamycin
* Drug: Trofosfamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically established metastatic (N+ or M1 = stage IV) or non-resectable soft tissue sarcoma· Grading II/III (Guillou et al. J Clin Oncol 1997) At least 1 measurable tumor parameter according to RECIST criteria Evidence of progression or primary manifestation (except osseous metastases and pleural effusion) No previous radiation therapy of the only measurable lesion No previous chemotherapy for metastatic disease; previous adjuvant chemotherapy is permitted if there was no progression of the disease within a period of 6 months Patients aged 60 years and beyond Written patient informed consent ECOG Status 0-2 Granulocytes >= 2 x 10**9/l and thrombocytes >= 100 x 10**/l Serum creatinine, bilirubin < 1.5 times the upper limit of normal value, albumin > 25 g/l No severe comorbidity including psychosis or any previous history of uncontrolled cardiovascular disease Normal left-ventricular function by echocardiography or MUGA scan No symptomatic CNS metastases Willingness to receive regular follow-up examinations Exclusion Criteria: Histological grading of malignancy: G I Histology of gastrointestinal stromal tumor, chondrosarcoma, uterine stromal sarcoma, mesothelioma, neuroblastoma, osteosarcoma, Ewing´s sarcoma/PNET, desmoplastic round cell tumor, embryonal rhabdomyosarcoma, alveolar soft tissue sarcoma Less than 5 years free of secondary malignancy except adequately treated carcinoma in situ (CIS) of the cervix, the bladder urothelium, basal cell carcinoma, or adenoma of the colon including pTIS, pTIN

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Adriamycin mono | Drug: Adriamycin<br>* 60 mg/m2, d1, W d22<br>|
| Experimental: 2<br>Trofosfamide | Drug: Trofosfamide<br>* 300 mg absolute d1-7, followed by 150 mg absolute continuously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival after 6 months | Progression-free survival after 6 months | after 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Grade III/IV toxicity Objective remission rate according to RECIST criteria Overall survival • Quality of life according to EORTC QLQ-30 | Grade III/IV toxicity Objective remission rate according to RECIST criteria Overall survival Quality of life according to EORTC QLQ-30 |  |