A Study of Palifosfamide Tris Plus Doxorubicin Versus Doxorubicin in Unresectable or Metastatic Soft-tissue Sarcoma

NCT00718484 | Unknown Phase 2

• 1 other identifier: IPM2002
• Study Type: interventional
• Target: 67
• Locations: 3 countries
• Sites: 23

Brief Summary

This is a randomized, controlled trial to evaluate the clinical benefit of palifosfamide tris administered with doxorubicin in combination, compared with single-agent doxorubicin administered in subjects diagnosed with unresectable or metastatic soft-tissue sarcoma (STS). Subjects who meet the entry criteria will be randomized into 1 of 2 arms: either to receive palifosfamide tris plus doxorubicin or treatment with single-agent doxorubicin. Subjects will be anthracyclin naïve.

Conditions

Soft Tissue Sarcoma

Keywords

Sarcoma; Soft Tissue Sarcoma; Doxorubicin; anthracyclin; Palifosfamide; IFOS

Outcome Measures

Primary Outcomes (1)

• The primary efficacy analysis will be conducted on the intent-to-treat (ITT) population. All attempts will be made to conduct assessment of disease status every 6 weeks until progression of disease or initiating off protocol anti cancer therapies.

  Every 6 weeks until progression

Study Arms (2)

A

EXPERIMENTAL

On Day 1 of each cycle (21 days), 150 mg/m2 IV (intravenous) palifosfamide tris and 75 mg/m2 IV doxorubicin are administered on the same day. Doxorubicin administration will be initiated approximately 60 minutes after the completion of palifosfamide tris dosing. Palifosfamide tris alone is administered on Days 2 and 3, every 3 weeks (one 21-day cycle).

Drug: Palifosfamide Tris and Doxorubicin

B

ACTIVE COMPARATOR

On Day 1 of each cycle, 75 mg/m2 doxorubicin is administered IV.

Drug: Doxorubicin

Interventions

Palifosfamide Tris and Doxorubicin DRUG

On Day 1 of each cycle (21 days), 150 mg/m2 IV (intravenous) palifosfamide tris and 75 mg/m2 IV doxorubicin are administered on the same day. Doxorubicin administration will be initiated approximately 60 minutes after the completion of palifosfamide tris dosing. Palifosfamide tris alone is administered on Days 2 and 3, every 3 weeks (one 21-day cycle).

A

Doxorubicin DRUG

On Day 1 of each cycle, 75 mg/m2 doxorubicin is administered IV.

B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years
• Histological or cytological documentation of sarcoma (excluding alveolar soft-part sarcoma, chondrosarcoma, dermatofibrosarcoma, Ewing sarcoma, GIST, Kaposi sarcoma, mixed mesodermal tumor, osteosarcoma, radiation induced sarcomas, and unresectable low grade liposarcoma) who have failed ≤2 prior regimens including adjuvant therapy, or ≤1 prior regimen for metastatic/unresectable disease, and for whom treatment with doxorubicin is considered medically acceptable. Prior treatment with IFOS is acceptable.
• Have measurable disease as per RECIST criteria (Appendix 2)
• ECOG Performance Status of 0 or 1 (Appendix 3)
• Anthracyclin naïve
• Life expectancy of ≥12 weeks
• Adequate bone marrow, liver, and renal function, as assessed by the following laboratory requirements conducted within 14 days prior to dosing:
• Hemoglobin ≥9.0 g/dL
• Absolute neutrophil count (ANC) ≥1,500/mm3
• Platelet count 100,000/mm3
• Total bilirubin ≤1.5×ULN (upper limit of normal)
• ALT and AST ≤2.5×ULN or 5×ULN with hepatic disease
• Partial thromboplastin \[PT\]-INR/activated partial thromboplastin time \[PTT\] \<1.5×ULN (≤2.0×ULN for subjects on anticoagulation prophylactic regimen). Subjects who are being therapeutically anticoagulated with an agent such as Coumadin (warfarin sodium) or heparin are allowed provided there is no prior evidence of underlying abnormality in coagulation parameters. If an interaction between study drug and anticoagulant is suspected, anticoagulation monitoring should be increased as appropriate.
• Serum creatinine ≤ULN
• Written informed consent must be obtained from a potential subject prior to the conduct of any study-specific procedures

You may not qualify if:

• Has any one of the following sarcoma sub types: alveolar soft-part sarcoma, chondrosarcoma, dermatofibrosarcoma, Ewing sarcoma, GIST, Kaposi sarcoma, mixed mesodermal tumor, osteosarcoma, radiation induced sarcomas, and unresectable low grade liposarcoma.
• Clinically evident congestive heart failure \>Class II of the New York Heart Association (NYHA) guidelines (Appendix 4)
• Serious, clinically significant cardiac arrhythmias, defined as the existence of an absolute arrhythmia, or ventricular arrhythmias classified as Lown III, IV, or V (Appendix 4)
• History and/or signs of active coronary artery disease/ischemia with or without angina pectoris
• Serious myocardial dysfunction defined as scintigraphically (MUGA \[multiple gated acquisition scan\], myocardial scintigram) or ultrasound-determined absolute left ventricular ejection fraction (LVEF) \<45%
• History of HIV infection
• Prior nephrectomy or history of urinary tract obstruction
• Active, clinically serious infection requiring systemic antibacterial, antifungal, or antiviral therapy
• Any major surgery within 3 weeks prior to start of treatment
• Metastatic brain or meningeal tumors, unless the subject is \>6 months from definitive therapy and has a negative imaging study within 4 weeks of study entry. In addition, the subject must not be undergoing acute steroid therapy or taper (chronic steroid therapy is acceptable, provided the dose is stable for 1 month prior to study start, and following screening radiographic studies).
• Previous malignancy (except cervical carcinoma in situ, adequately treated basal cell carcinoma, or superficial bladder tumors \[Ta, Tis, \& T1\] or other malignancies curatively treated \>5 years prior to entry)
• Pregnancy or lactation
• Substance abuse or medical, psychological, or social conditions that may interfere with the subject's participation in the study or evaluation of the study results
• Any condition that is unstable or could jeopardize the safety of a subject and his/her compliance with the protocol requirements
• In addition, use of the following therapies and medications-prior or concomitant-would exclude a subject from this study:

Sponsors & Collaborators

• Alaunos Therapeutics: lead

Study Sites (23)

Unknown Facility

Santa Monica, California, United States

Location

Unknown Facility

Washington D.C., District of Columbia, United States

Location

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Tampa, Florida, United States

Location

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Coeur d'Alene, Idaho, 83814, United States

Location

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Chicago, Illinois, United States

Location

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Park Ridge, Illinois, United States

Location

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Iowa City, Iowa, United States

Location

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Lenaxa, Kansas, United States

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Albuquerque, New Mexico, United States

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New York, New York, United States

Location

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Durham, North Carolina, United States

Location

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Portland, Oregon, United States

Location

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Philadelphia, Pennsylvania, United States

Location

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Memphis, Tennessee, United States

Location

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Nashville, Tennessee, United States

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San Antonio, Texas, United States

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Salt Lake City, Utah, United States

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Seattle, Washington, United States

Location

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Milan, Italy

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Padua, Italy

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Torino, Italy

Location

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Cluj-Napoca, 400015, Romania

Location

Unknown Facility

Lasi, Romania

Location

MeSH Terms

Conditions

Sarcoma

Interventions

Ifosfamide; Doxorubicin

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Jonathan J Lewis, MD, PhD

  ZIOPHARM Oncology, Inc

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2008
• First Posted: July 18, 2008
• Study Start: August 1, 2008
• Primary Completion: April 1, 2012
• Study Completion: April 1, 2014
• Last Updated: January 30, 2014

Record last verified: 2014-01

Locations

RO (2); IT (3); US (18)