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
Palifermin is similar to a protein keratinocyte growth factor (KGF) that is naturally made
in your body in small amounts. The function of palifermin is to stimulate the growth of
specific cells that form the tissue lining of your mouth and digestive tract. Damage to
these cells results in the breakdown of the normal protective barrier that these cells
usually provide, potentially resulting in infection.
If you are eligible to take part in this study, you will be randomly assigned (as in the
toss of a coin) to receive either palifermin or placebo by vein 3 days before each cycle of
chemotherapy. This will be done for 18 weeks (a total of 12 injections). A placebo is a
substance that looks like the study drug, but which has no active ingredients. The infusion
time will last 15-30 seconds. At the beginning of the study, for every 3 patients who are
enrolled on this study, 2 of the 3 will receive palifermin. Neither you nor the study
doctor will know which study drug you are assigned to receive.
Within 1 or 2 days before you receive your first dose of palifermin and between 48 to 72
hours after you receive your first dose of palifermin, additional non-invasive optical
imaging procedures may be performed. The purpose of these imaging procedures is to evaluate
the effects of palifermin on mucosa (mucosal thickness). The types of optical imaging that
may be done include optical coherence tomography (OCT), fluorescence and reflectance
spectroscopy, or confocal microscopy. The oral cavity will be inspected and photographed.
A probe about the size of a pen will be placed on one or two sites of oral buccal mucosa. A
beam of light will then be directed to the oral tissue and optical signals will be collected
from each site. This will take about 1 minute for each site. Before using the probe for
each new participant, it will be disinfected per standard practice.
You will receive adriamycin with ifosfamide or cisplatin chemotherapy. Adriamycin will be
given as a continuous infusion through your central venous catheter (CVC) for 3 days.
Ifosfamide will be given intravenously (intravenously (IV)--through a needle in your vein)
through your CVC over 3 hours, every day for 4 days. Mesna will be given as a 24-hour IV
infusion through your CVC every day for 4 days through the same catheter. Mesna is used to
protect against bladder-related side effects. For patients with certain types of sarcoma,
vincristine will be given through the catheter by rapid infusion on Day 1 only. In patients
with bone sarcoma, cisplatin will be given on the first day as IV or intra-arterial infusion
over around 4 hours instead of ifosfamide.
You will need to come in to M. D. Anderson every 3 weeks for about 4 to 5 months during the
treatment period, unless your doctor decides you need to come in more frequently. At these
visits, you will have your vital signs measured and routine blood tests (about 3 teaspoons
each) will be performed. In addition, you may have your oral cavity examined and
photographed before and after receiving the study drug. Every effort will be made to take
photographs in which you cannot be identified.
Additional blood samples (about 3 teaspoons) will be taken before each cycle and as
frequently as needed to measure your blood count and other tests to monitor the drug side
effects and treatment effects. By the end of the study, you will have given about 10
tablespoons of blood. This amount includes the optional blood draws should you choose to
allow it to be drawn.
You will be responsible for notifying study staff (at your doctors visits or over the phone
with the study staff) of any side effects you experience or medications (over the counter or
prescription) that you take during the treatment period. You will also be required to
notify any other doctors (separate from the study doctors) you see that you are
participating in this research study.
If your anemia becomes severe while you are on study, then a transfusion may be recommended.
If mucositis develops, the prohibited medicines can be allowed for treatment of the
condition. If you experience an intolerable side effect while on study, you may be taken
off study. If you leave the study early for any reason, your doctor will continue to follow
your progress for 4 weeks and will access your medical records for a minimum of 1 year after
the last dose of study drug (either palifermin or placebo) was given.
At your end of study visit, you will be evaluated for your disease status with imaging
studies [computed tomography (CT) scans or magnetic resonance images (MRI)] and your weight
and vitals signs will be measured. You will report any medications you have taken since
your last visit and any side effects or blood transfusion that you have had. You will also
have a final blood draw (about 3 teaspoons) for routine tests.
The total length of your involvement in this study is expected to be about 18 weeks (4 to 5
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention
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.
Saroj Vadhan-Raj, M.D.
University of Texas MDAnderson Cancer Center
United States: Food and Drug Administration
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