Evaluate PKs and Efficacy Assessment of Palifermin in Patients With Sarcoma

NCT00267046 | Completed Phase 2 Results DMC

• 1 other identifier: 2004-0511
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

Brief Summary

Primary:

1. 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. 2.To evaluate the pharmacokinetics (PK) of palifermin when given pre chemotherapy.
3. 3.To evaluate the safety profile of palifermin when combined with multicycle chemotherapy.
4. 4.To evaluate the biologic effect of palifermin on oral mucosa.
5. 5.To investigate potential biomarker development by biochemical analysis in blood cells, serum, and plasma.
6. 6.To investigate the effects of genetic variation in mucositis genes, drug metabolism genes, and drug target genes on patient response to the treatment regimen.

Conditions

Sarcoma; Oral Mucositis

Keywords

Sarcoma; Soft Tissue Sarcoma; Oral Mucositis; Doxorubicin; Adriamycin; Ifosfamide; Palifermin; Vincristine; Cisplatin; Placebo

Outcome Measures

Primary Outcomes (2)

• Cumulative Incidence Rate of Oral Mucositis

  Cumulative incidence of World Health Organization (WHO) grade 2 or \> mucositis (moderate to severe) in participants completing up to 6 blinded cycles. Rate defined as participants who had Grade 2 or \> divided by total number of participants who completed up to 6 blinded cycles. WHO Criteria of Grade 1: possible buccal mucosal scalloping with/without erythema; No ulcers; swallows solid diet. Grade 2: ulcers with or without erythema; swallow solid diet. Grade 3: ulcers with/without (extensive) erythema; swallow liquid, not solid diet. Grade 4: mucositis to extent alimentation not possible.

  Within 6 blinded cycles (3-week cycles), up to 18 weeks.

• Median Maximum Score for Patient Reported Outcomes in 2 Blinded Cycles

  Median maximum score (0 to 10, with 10 being the worst) for participant-reported outcomes in the first 2 blinded cycles for Mouth Pain, Overall Mouth and Throat Soreness, and Rectal Soreness while median maximum score for Swallowing, Drinking and Eating Difficulty (0 to 4, with 4 being the difficult).

  Within the first 2 blinded cycles (3-week cycles), up to 6 weeks.

Study Arms (2)

Palifermin

EXPERIMENTAL

Palifermin + Chemotherapy (Adriamycin (Doxorubicin)+ Ifosfamide (AI) or Adriamycin (Doxorubicin) + Cisplatin (AP) Regimen); Palifermin 180 mcg/kg 3 days prior to chemotherapy; Adriamycin 30 mg/m\^2 intravenous (IV) for 72 hours starting Days 0 for total 90 mg/m\^2. Ifosfamide 2.5 g/m\^2 IV bolus Days 0-3 (total 10 g/m\^2); Vincristine 2 mg IV Day 0. AP=Doxorubicin (Adriamycin) + Cisplatin: Palifermin 180 mcg/kg 3 days prior to chemotherapy; Adriamycin 30 mg/m\^2 IV continuous infusion for 72 hours starting Day 0(total = 90 mg/m\^2); Cisplatin 120 mg/m\^2 on day 0.

Drug: Palifermin; Drug: Adriamycin (Doxorubicin); Drug: Ifosfamide; Drug: Vincristine; Drug: Cisplatin

Placebo

PLACEBO COMPARATOR

Placebo + Chemotherapy (AI or AP Regimen); AI = Doxorubicin (Adriamycin) + Ifosfamide: A single dose placebo prior to chemotherapy; Adriamycin 30 mg/m\^2 intravenous (IV) for 72 hours starting Days 0 for total 90 mg/m\^2. Ifosfamide 2.5 g/m\^2 IV bolus Days 0-3 (total 10 g/m\^2); Vincristine 2 mg IV Day 0. AP=Doxorubicin (Adriamycin) + Cisplatin: A single dose placebo 3 days prior to chemotherapy; Adriamycin 30 mg/m\^2 IV continuous infusion for 72 hours starting Day 0(total = 90 mg/m\^2); Cisplatin 120 mg/m\^2 on day 0.

Drug: Placebo; Drug: Adriamycin (Doxorubicin); Drug: Ifosfamide; Drug: Vincristine; Drug: Cisplatin

Interventions

Palifermin DRUG

180 mcg/kg 3 days prior to chemotherapy

Palifermin

Placebo DRUG

Single dose 3 days prior to chemotherapy

Placebo

Adriamycin (Doxorubicin) DRUG

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).

Also known as: Adriamycin

Palifermin; Placebo

Ifosfamide DRUG

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.

Palifermin; Placebo

Vincristine DRUG

2 mg IV on day 0, for patients with small cell histology receiving the AI Regimen.

Palifermin; Placebo

Cisplatin DRUG

120 mg/m\^2 on day 0, for patients receiving the AP Regimen.

Also known as: CDDP, Platinol

Palifermin; Placebo

Eligibility Criteria

• Age: 15 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• 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.
• Karnofsky Performance Status \>/= 80.
• Signed informed consent form.

You may not qualify if:

• Pregnant or lactating women.
• Patients with comorbid condition which renders patients at high risk of treatment complication.
• Patients with metastatic disease to CNS.
• 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.
• 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.
• Prior surgery or radiotherapy (RT) within 2 weeks of study entry.
• Prior treatment with palifermin, or other keratinocyte growth factors (eg, KGF-2).
• 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).
• Known sensitivity to any of the products to be administered during this study, including Escherichia coli-derived products.
• Psychological, social, familial, or geographical reasons that would prevent scheduled visits and follow-up.
• Patients with a history of pancreatitis.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

U.T.M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Vadhan-Raj S, Trent J, Patel S, Zhou X, Johnson MM, Araujo D, Ludwig JA, O'Roark S, Gillenwater AM, Bueso-Ramos C, El-Naggar AK, Benjamin RS. Single-dose palifermin prevents severe oral mucositis during multicycle chemotherapy in patients with cancer: a randomized trial. Ann Intern Med. 2010 Sep 21;153(6):358-67. doi: 10.7326/0003-4819-153-6-201009210-00003.

  PMID: 20855800 RESULT

Related Links

• The University of Texas M.D.Anderson Cancer Center

MeSH Terms

Conditions

Sarcoma; Stomatitis

Interventions

Fibroblast Growth Factor 7; Doxorubicin; Ifosfamide; Vincristine; Cisplatin

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Mouth Diseases; Stomatognathic Diseases

Intervention Hierarchy (Ancestors)

Fibroblast Growth Factors; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Results Point of Contact

• Title: Saroj Vadhan-Raj, MD/Professor
• Organization: UT MD Anderson Cancer Center

xzhou@mdanderson.org

713-792-7966

Study Officials

• Saroj Vadhan-Raj, M.D.

  University of Texas MDAnderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2005
• First Posted: December 20, 2005
• Study Start: December 1, 2005
• Primary Completion: July 1, 2009
• Study Completion: July 1, 2009
• Last Updated: May 16, 2012
• Results First Posted: May 16, 2012

Record last verified: 2012-04

Locations

US (1)