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
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- M.D. Anderson Cancer Center
- Enrollment
- 49
- Locations
- 1
- Primary Endpoint
- Cumulative Incidence Rate of Oral Mucositis
Study Overview
Brief Summary
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.
Detailed Description
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 15 Years to 65 Years (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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 >/=
- •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.
Arms & Interventions
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.
Intervention: Palifermin (Drug)
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.
Intervention: Adriamycin (Doxorubicin) (Drug)
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.
Intervention: Ifosfamide (Drug)
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.
Intervention: Vincristine (Drug)
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.
Intervention: Cisplatin (Drug)
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.
Intervention: Placebo (Drug)
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.
Intervention: Adriamycin (Doxorubicin) (Drug)
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.
Intervention: Ifosfamide (Drug)
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.
Intervention: Vincristine (Drug)
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.
Intervention: Cisplatin (Drug)
Outcomes
Primary Outcomes
Cumulative Incidence Rate of Oral Mucositis
Time Frame: Within 6 blinded cycles (3-week cycles), up to 18 weeks.
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.
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).
Secondary Outcomes
No secondary outcomes reported