Evaluate PKs and Efficacy Assessment of Palifermin in Patients With Sarcoma
Condition: Sarcoma; Oral Mucositis
MeSH terms: Sarcoma; Mucositis; Stomatitis
Intervention: Palifermin; Placebo; Adriamycin (Doxorubicin); Ifosfamide; Vincristine; Cisplatin
Intervention description: 180 mcg/kg 3 days prior to chemotherapy; Single dose 3 days prior to chemotherapy; 30 mg/m^2 IV continuous infusion for 72 hours; days 0, 1, 2 (infusion completing on day 3) (total dose = 90 mg/m^2).; 2.5 g/m^2 IV bolus over 3 hours, days 0,1, 2, 3 (total dose = 10 g/m^2); for patients receiving the AI Regimen.; 2 mg IV on day 0, for patients with small cell histology receiving the AI Regimen.; 120 mg/m^2 on day 0, for patients receiving the AP Regimen.
Intervention MeSH terms: Doxorubicin; Liposomal doxorubicin; Vincristine; Ifosfamide
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 49.0
Sex: All
Minimum age: 15 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Sarcoma; Soft Tissue Sarcoma; Oral Mucositis; Doxorubicin; Adriamycin; Ifosfamide; Palifermin; Vincristine; Cisplatin; Placebo

Summary:

      Primary:

        1. To evaluate the preliminary efficacy of palifermin in reducing the incidence and
           severity of oral mucositis (OM) in patients with sarcoma receiving multicycle
           chemotherapy.

        2. To evaluate the pharmacokinetics (PK) of palifermin when given pre chemotherapy.

        3. To evaluate the safety profile of palifermin when combined with multicycle chemotherapy.

      Exploratory:

        1. To evaluate the biologic effect of palifermin on oral mucosa.

        2. To investigate potential biomarker development by biochemical analysis in blood cells,
           serum, and plasma.

        3. To investigate the effects of genetic variation in mucositis genes, drug metabolism
           genes, and drug target genes on patient response to the treatment regimen.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients with sarcoma which is locally advanced, at high risk for relapse or
             metastatic for whom treatment with high dose doxorubicin (90 mg/m2) with ifosfamide
             (AI) or cisplatinum (AP) is indicated.

          2. Patients (male and female) with childbearing potential (defined as not post-menopausal
             for 12 months, negative blood pregnancy test, or no previous surgical sterilization)
             must use adequate birth control.

          3. Adequate hematologic (Absolute neutrophil count (ANC)>/= 1500/mm^3, >/= Hgb 10gm/dL,
             platelet count >/= 150,000/mm^3), renal (serum creatinine </= 1.5mg/dL), hepatic
             (serum bilirubin count </= 1.5 * normal and SGPT < 3 * normal) functions.

          4. Karnofsky Performance Status >/= 80.

          5. Signed informed consent form.

        Exclusion Criteria:

          1. Pregnant or lactating women.

          2. Patients with comorbid condition which renders patients at high risk of treatment
             complication.

          3. Patients with metastatic disease to CNS.

          4. Patient has uncontrolled angina, congestive heart failure (New York Heart Association
             > class II or known ejection fraction < 40%), uncontrolled cardiac arrhythmia, acute
             myocardial infarction within 3 months or has uncontrolled hypertension.

          5. Patient has an active seizure disorder. Patients with a previous history of seizure
             disorders will be eligible for the study, if they have had no evidence of seizure
             activity, and they have been free of antiseizure medication for the previous 5 years.

          6. Prior surgery or radiotherapy (RT) within 2 weeks of study entry.

          7. Prior treatment with palifermin, or other keratinocyte growth factors (eg, KGF-2).

          8. Thirty days or less since receiving an investigational product or device in another
             clinical trial. Current enrollment in another clinical trial is not permitted unless
             the sole purpose of the trial is to obtain post-treatment data on the subject (eg,
             long-term follow-up or survival data).

          9. Known sensitivity to any of the products to be administered during this study,
             including Escherichia coli-derived products.

         10. Psychological, social, familial, or geographical reasons that would prevent scheduled
             visits and follow-up.

         11. Patients with a history of pancreatitis.