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

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

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).

Study Overview

• Status: Unknown
• Conditions: Sarcoma, Soft Tissue
• Intervention / Treatment: Drug: Adriamycin; Drug: Trofosfamide

Detailed Description

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)

• Study Type: Interventional
• Enrollment (Anticipated): 117
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Kiel, Germany, 24105
    • University Medical Center , Comprehensive Cancer Center North, Christian-Albrechts-University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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
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

Collaborators and Investigators

• Sponsor: University Hospital Schleswig-Holstein
• Collaborators: Arbeitsgemeinschaft fur Internistische Onkologie; French Sarcoma Group; German Sarcoma Group
• Investigators: Principal Investigator: Joerg T. Hartmann, MD, University Medical Center , Comprehensive Cancer Center North, Christian-Albrechts-University

Study record dates

Study Major Dates

• Study Start: August 1, 2004
• Primary Completion (Anticipated): October 1, 2013
• Study Completion (Anticipated): October 1, 2013

Study Registration Dates

• First Submitted: September 13, 2005
• First Submitted That Met QC Criteria: September 13, 2005
• First Posted (Estimate): September 20, 2005

Study Record Updates

• Last Update Posted (Estimate): January 8, 2013
• Last Update Submitted That Met QC Criteria: January 7, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Doxorubicin; Liposomal doxorubicin; Trofosfamide
• Other Study ID Numbers: jth_001