Study of Palifosfamide-tris in Combination With Doxorubicin in Patients With Front-line Metastatic Soft Tissue Sarcoma

Study Overview
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Brief Summary
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This is an international, randomized, double-blind, placebo-controlled trial to evaluate the clinical efficacy of palifosfamide-tris administered with doxorubicin in combination, compared with doxorubicin administered with placebo in front-line patients diagnosed with metastatic soft tissue sarcoma (STS).

Official Title
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A Phase III Multicenter, International, Randomized, Double-blind, Placebo-controlled Study of Doxorubicin Plus Palifosfamide-tris vs. Doxorubicin Plus Placebo in Patients With Front-line Metastatic Soft Tissue Sarcoma.

Conditions
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Soft Tissue Sarcoma

Intervention / Treatment
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* Drug: doxorubicin in combination with palifosfamide-tris
* Drug: doxorubicin in combination with placebo


Participation Criteria
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Eligibility Criteria
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To be eligible, each patient must meet EACH of the following criteria: Age ≥18 years. Documented soft tissue sarcoma Metastatic disease for which the patient has not received any prior treatment, and for whom treatment with doxorubicin is considered medically acceptable. ECOG Performance Status of 0, 1 or 2 Adequate bone marrow and organ function based on the results of protocol- specified laboratory tests Male and female patients must agree to use a highly reliable method of birth control during study participation. Able to provide informed consent To be eligible, each patient must meet NONE of the following criteria: Specific sarcoma histological subtypes including GIST and Ewing's sarcoma. Systemic therapy for the treatment of metastatic sarcoma, prior to or during the study. However, patients may have received neo-adjuvant/adjuvant Gemzar and Taxotere chemotherapy for their primary sarcoma, prior to the development of metastatic disease Any prior anthracycline use. Known allergy to any of the study drugs or their excipients. Any unstable or clinically significant concurrent medical condition that would, in the opinion of the investigator, jeopardize the safety of a patient and/or their compliance with the protocol, based on screening tests, physical examination and medical history (as specifically defined in the clinical protocol). Myocardial dysfunction defined as left ventricular ejection fraction (LVEF) <50%. Documented metastases to brain or meninges. Any malignancy other than sarcoma within the last 5 years prior to screening, with the exception of cervical carcinoma in situ, basal cell carcinoma, or superficial bladder tumors (Ta, Tis, or T1) that have been successfully and curatively treated with no evidence of recurrent or residual disease. Currently pregnant or nursing. Radiotherapy with curative intent within 4 weeks of first dose of study drug.

Ages Eligible for Study
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Minimum Age: 18 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: doxorubicin plus palifosfamide-tris<br> | Drug: doxorubicin in combination with palifosfamide-tris<br>* palifosfamide-tris: 150 mg/m2 3 days every 21 days for a maximum of 6 cycles. doxorubicin: 75 mg/m2 1 day every 21 days for a maximum of 6 cycles.<br>|
| Active Comparator: doxorubicin plus placebo<br> | Drug: doxorubicin in combination with placebo<br>* doxorubicin: 75 mg/m2 of doxorubicin 1 day every 21 days for a maximum of 6 cycles. placebo: 250 mL of normal saline 3 days every 21 days for a maximum of 6 cycles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival followed by Overall Survival |  | assessed every 6 weeks for 22 weeks, then 8 weeks for 6 months/until progression, then every 12 weeks until then death | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Life, as assessed by EORTC QLQ-C30 and EQ-5D questionnaires |  | assessed every 6 weeks for 22 weeks, then 8 weeks for 6 months, then every 12 weeks until death | 
| Safety and Tolerability as evaluated using CTCAE v 4.0 |  | 22 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic, Front line