Evaluate PKs and Efficacy Assessment of Palifermin in Patients With Sarcoma - Full Text View

Purpose

Primary:

To evaluate the preliminary efficacy of palifermin in reducing the incidence and severity of oral mucositis (OM) in patients with sarcoma receiving multicycle chemotherapy.
To evaluate the pharmacokinetics (PK) of palifermin when given pre chemotherapy.
To evaluate the safety profile of palifermin when combined with multicycle chemotherapy.

Exploratory:

To evaluate the biologic effect of palifermin on oral mucosa.
To investigate potential biomarker development by biochemical analysis in blood cells, serum, and plasma.
To investigate the effects of genetic variation in mucositis genes, drug metabolism genes, and drug target genes on patient response to the treatment regimen.

Condition	Intervention	Phase
Sarcoma Oral Mucositis	Drug: Palifermin Drug: Placebo Drug: Adriamycin (Doxorubicin) Drug: Ifosfamide Drug: Vincristine Drug: Cisplatin	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Prevention
Official Title:	A Phase II Study to Evaluate the Pharmacokinetics, Safety, and Obtain a Preliminary Efficacy Assessment of Palifermin in Patients With Sarcoma Receiving Multicycle Chemotherapy With Doxorubicin and Ifosfamide

Resource links provided by NLM:

MedlinePlus related topics: Cancer Soft Tissue Sarcoma

Drug Information available for: Vincristine sulfate Ifosfamide Cisplatin Doxorubicin Doxorubicin hydrochloride Palifermin

U.S. FDA Resources

Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:

Cumulative Incidence Rate of Oral Mucositis [ Time Frame: Within 6 blinded cycles (3-week cycles), up to 18 weeks. ] [ Designated as safety issue: No ]
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.
Median Maximum Score for Patient Reported Outcomes in 2 Blinded Cycles [ Time Frame: Within the first 2 blinded cycles (3-week cycles), up to 6 weeks. ] [ Designated as safety issue: No ]
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).

Enrollment:	49
Study Start Date:	December 2005
Study Completion Date:	July 2009
Primary Completion Date:	July 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Palifermin 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 180 mcg/kg 3 days prior to chemotherapy Drug: Adriamycin (Doxorubicin) 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). Other Name: Adriamycin Drug: Ifosfamide 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. Drug: Vincristine 2 mg IV on day 0, for patients with small cell histology receiving the AI Regimen. Drug: Cisplatin 120 mg/m^2 on day 0, for patients receiving the AP Regimen. Other Names: CDDP Platinol
Placebo Comparator: Placebo 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 Single dose 3 days prior to chemotherapy Drug: Adriamycin (Doxorubicin) 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). Other Name: Adriamycin Drug: Ifosfamide 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. Drug: Vincristine 2 mg IV on day 0, for patients with small cell histology receiving the AI Regimen. Drug: Cisplatin 120 mg/m^2 on day 0, for patients receiving the AP Regimen. Other Names: CDDP Platinol

Arms

Assigned Interventions

Experimental: Palifermin

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

180 mcg/kg 3 days prior to chemotherapy

Drug: Adriamycin (Doxorubicin)

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).

Other Name: Adriamycin

Drug: Ifosfamide

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.

Drug: Vincristine

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

Drug: Cisplatin

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

Other Names:

CDDP
Platinol

Placebo Comparator: Placebo

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

Single dose 3 days prior to chemotherapy

Drug: Adriamycin (Doxorubicin)

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).

Other Name: Adriamycin

Drug: Ifosfamide

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.

Drug: Vincristine

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

Drug: Cisplatin

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

Other Names:

CDDP
Platinol

Show Detailed Description

Eligibility

Ages Eligible for Study:	15 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00267046

Locations

United States, Texas
U.T.M.D. Anderson Cancer Center
Houston, Texas, United States, 77030

Sponsors and Collaborators

M.D. Anderson Cancer Center

Investigators

Principal Investigator:

Saroj Vadhan-Raj, M.D.

University of Texas MDAnderson Cancer Center

More Information

Additional Information:

The University of Texas M.D.Anderson Cancer Center This link exits the ClinicalTrials.gov site

Publications:

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.

Responsible Party:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00267046 History of Changes
Other Study ID Numbers:	2004-0511
Study First Received:	December 19, 2005
Results First Received:	January 18, 2012
Last Updated:	April 17, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:

Sarcoma
Soft Tissue Sarcoma
Oral Mucositis
Doxorubicin
Adriamycin

Ifosfamide
Palifermin
Vincristine
Cisplatin
Placebo

Additional relevant MeSH terms:

Stomatitis
Mucositis
Sarcoma
Mouth Diseases
Stomatognathic Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Isophosphamide mustard
Cisplatin
Doxorubicin
Ifosfamide

Vincristine
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on May 23, 2013