Aprepitant in Preventing Nausea and Vomiting in Patients Who Are Undergoing a Stem Cell Transplant

Official Title: “A Pilot Study of Aprepitant vs. Placebo Combined With Standard Antiemetics for the Control of Nausea and Vomiting During Hematopoietic Cell Transplatation(HCT)”

RATIONALE: Antiemetic drugs, such as aprepitant, ondansetron, and dexamethasone, may help lessen or prevent nausea and vomiting in patients undergoing a stem cell transplant.

PURPOSE: This randomized clinical trial is studying aprepitant, ondansetron, and dexamethasone to see how well they work compared to placebo, ondansetron, and dexamethasone in preventing nausea and vomiting in patients who are undergoing a stem cell transplant.

OBJECTIVES:

Primary - Compare the efficacy of standard antiemetic therapy comprising ondansetron and dexamethasone combined with either aprepitant or placebo in controlling nausea and vomiting, as determined by the number of retch/emesis-free days, in patients undergoing hematopoietic stem cell transplantation.

Secondary - Determine the safety of aprepitant in these patients. - Compare nausea, appetite, taste changes, nutritional intake, and mucositis in patients treated with these regimens. - Determine the pharmacokinetics of cyclophosphamide, carboxyethylphosphoramide mustard, hydroxycyclophylamide, and aprepitant in these patients.

OUTLINE: This is a randomized, placebo-controlled, single-blind, pilot study. Patients are randomized to 1 of 2 treatment arms. - Arm I: Beginning on the first day of conditioning chemotherapy, patients receive oral aprepitant once daily and standard antiemetic therapy comprising oral or IV ondansetron and oral dexamethasone. - Arm II: Patients receive oral placebo once daily and standard antiemetic therapy as in arm I.

In both arms, treatment continues until day 4 after stem cell transplant in the absence of unacceptable toxicity.

After completion of study therapy, patients are followed until day 18.

PROJECTED ACCRUAL: A total of 40 patients (20 per treatment arm) will be accrued for this study.

Intervention(s) in this Clinical Trial

• Drug: aprepitant
  • Loading dose of 125 mg capsule once a day for one day, then maintenance dose of 80 mg capsule daily through Day +4 of Bone Marrow Transplant
• Drug: dexamethasone
  • For Cyclophosphamide Total Body Irradiation(CyTBI) patients: Dexamethasone study drug 1 capsule PO daily, 1 hour prior to chemotherapy with aprepitant on total body irradiation(TBI) and cyclophosphamide chemotherapy days; For Busulfan Cyclophosphamide(BuCy) patients: Dexamethasone 1 capsule orally once daily, discontinue after last dose of chemotherapy.
• Drug: ondansetron
  • For CyTBI patients: Ondansetron 8 mg orally evert 12 hours, begin 1 hour prior to first TBI dose and discontinue after last dose; then Ondansetron 8 mg IV every 12 hours X 4 doses, begin 30 minutes prior to first cyclophosphamide chemotherapy; For BuCy patients: Ondansetron 8 mg orally every 6 hours, begin 1 hour prior to first busulfan dose and discontinue after last busulfan dose is given. then: Ondansetron 8 mg IV Q 12 hours X 4 doses, begin 30 minutes prior to first cyclophosphamide chemotherapy
• Drug: placebo
  • Loading dose of 125 mg capsule once a day for one day, then maintenance dose of 80 mg capsule daily through Day +4 of Bone Marrow Transplant

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: Aprepitant
• Placebo Comparator: sugar pill
  • Loading dose of 125 mg capsule once a day for one day, then maintenance dose of 80 mg capsule daily through Day +4 of Bone Marrow Transplant

Primary Measures

• Number of Emesis Free Participants During the Study Period.
  • Time Frame: Up to three weeks
    Safety Issue?: No

Secondary Measures

• Safety in Transplant Population
  • Time Frame: Up to three weeks
    Safety Issue?: Yes
• Effects on Nausea, Appetite and Taste Changes
  • Time Frame: Up to three weeks
    Safety Issue?: No
• Pharmacokinetic Interaction
  • Time Frame: Up to three weeks
    Safety Issue?: No

Inclusion:

• 18 years of age or greater
• must be scheduled for an autologous or allogeneic bone marrow or peripheral stem cell transplant
• Eastern Cooperative Oncology Group(ECOG) performance status < or = 2
• patients must have signed informed consent
• must be able to swallow tablets and capsules
• must be receiving a cyclophosphamide containing regimen.

Exclusion:

• patient has known sensitivity to aprepitant, ondansetron, or dexamethasone
• patient has received another investigational drug in the past 30 days
• patient has had emesis or requires antiemetic agents in the 48 hours prior to beginning conditioning therapy
• patient has taken neurokinin-1 antagonists for 14 days prior to enrollment
• patient is pregnant, has a positive serum human chorionic gonadotropin(hCg) or is lactating
• patient has serum creatinine level > or = 2*ULN
• patient has severe hepatic insufficiency (Child-Pugh score >9)
• patient drinks > 5 drinks/day for the last year
• patient with concurrent illness requiring systemic corticosteroid use other than planned dexamethasone during conditioning therapy

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: OHSU Knight Cancer Institute Other

Overall Clinical Trial Officials and Contacts

Joseph Bubalo, PharmD Principal Investigator OHSU Knight Cancer Institute  

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00248547

Study ID Number: CDR0000445452

ClinicalTrials.gov Identifier: NCT00248547

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database