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Effectiveness of Aprepitant in Addition to Ondansetron in the Prevention of Nausea and Vomiting Caused by Upper Abdominal Radiotherapy (AVERT)

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by University of Vermont
Sponsor:
Collaborators:
Mayo Clinic
Comprehensive Cancer Center of Wake Forest University
Norris Cotton Cancer Center
University of Massachusetts, Worcester
Information provided by (Responsible Party):
Steven Ades, University of Vermont
ClinicalTrials.gov Identifier:
NCT00970905
First received: August 25, 2009
Last updated: December 12, 2013
Last verified: December 2013
  Purpose

Severe nausea and/or vomiting in patients receiving radiotherapy to the upper abdomen is common despite having received pre-medication with ondansetron, a standard preventive treatment. This study aims to reduce the incidence of significant nausea and/or vomiting with the addition of the NK1-antagonist aprepitant to standard ondansetron treatment. This study will also assess the safety and tolerability of prolonged administration of aprepitant over the 4 to 6 week period of radiation treatment.


Condition Intervention Phase
Nausea
Vomiting
Drug: aprepitant
Drug: Ondansetron
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effectiveness of Aprepitant in Addition to Ondansetron in the Prevention of Nausea and Vomiting Caused by Fractionated Radiotherapy to the Upper Abdomen

Resource links provided by NLM:


Further study details as provided by University of Vermont:

Primary Outcome Measures:
  • Complete Response rate (no vomiting and no rescue anti-emetic therapy) [ Time Frame: overall period of radiation treatment (4-8 weeks) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Complete Response rate [ Time Frame: Cumulatively increasing time intervals from the start of radiation therapy (7 days, 14 days, 21 days, 28 days, 35 days, 42 days) ] [ Designated as safety issue: No ]
  • Proportion of patients who did not vomit [ Time Frame: Overall period of radiation therapy (4-8 weeks) ] [ Designated as safety issue: No ]
  • No Significant Nausea: The proportion of patients who did not experience any nausea ≥ 3 on 0 - 10 scale [ Time Frame: Overall period of radiation treatment (4-8 weeks) ] [ Designated as safety issue: No ]
  • No Nausea: The proportion of patients who did not experience any nausea. Nausea = 0 on 0 - 10 scale [ Time Frame: Overall period of radiation treatment (4-8 weeks) ] [ Designated as safety issue: No ]
  • Complete Protection: The proportion of patients who did not vomit, require rescue therapy, or have nausea ≥ 3 on 0 - 10 scale [ Time Frame: Overall period of radiation treatment (4-8 weeks) ] [ Designated as safety issue: No ]
  • Total Protection: The proportion of patients who did not vomit, require rescue therapy, or have any nausea (Nausea = 0 on 0 - 10 scale). [ Time Frame: Overall period of radiation treatment (4-8 weeks) ] [ Designated as safety issue: No ]
  • Vomiting frequency: The frequency of vomiting (# episodes per week) in patients who did vomit at least once. [ Time Frame: Overall period of radiation treatment (4-8 weeks) ] [ Designated as safety issue: No ]
  • Nausea frequency: The frequency of nausea (Nausea > 0 in a given week/ number of weeks during overall period of radiation treatment) [ Time Frame: Overall period of radiation treatment (4-8 weeks) ] [ Designated as safety issue: No ]
  • Significant Nausea frequency: The frequency of significant nausea (Nausea ≥ 3 in a given week/ number of weeks during overall period of radiation treatment) [ Time Frame: Overall period of radiation treatment (4-8 weeks) ] [ Designated as safety issue: No ]
  • Frequency of rescue medication use: The number of days in which rescue medication was taken / number of days of radiotherapy [ Time Frame: overall period of radiation treatment (4-8 weeks) ] [ Designated as safety issue: No ]
  • Time to Failure: The time period in days from the start of radiation until the first vomiting episode or use of rescue medication for all patients and for the subset of patients who do not have a Complete Response. [ Time Frame: Overall period of radiation treatment (4-8 weeks) ] [ Designated as safety issue: Yes ]
  • All adverse events that occur during radiation treatment with assessment of severity (CTC v.3) and relationship to study drug. [ Time Frame: Overall period of radiation treatment (4-8 weeks) ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 61
Study Start Date: October 2009
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Aprepitant & Ondansetron Drug: aprepitant
aprepitant 125 mg po (Mondays), 80 mg po (Wednesdays), 80 mg po (Fridays) with doses scheduled 1-2 hours prior to the day's radiation fraction. Aprepitant will not be administered on weekend days. Aprepitant administration will continue until the last day of radiotherapy.
Other Name: Emend
Drug: Ondansetron
Ondansetron 8 mg po bid, with the morning dose scheduled 1-2 hours prior to the day's radiation fraction. Ondansetron will not be administered on weekend days. Ondansetron administration will continue until the last day of radiotherapy.
Other Name: Zofran

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Any patient with a diagnosis of malignancy localized to the upper abdomen and requiring chemoradiation or radiation alone.
  2. Receiving standard-fractionation radiation therapy (> 40 Gy) 3D-conformal radiation therapy or IMRT to a field involving the upper abdomen, either alone or combined with radiosensitizing 5FU, capecitabine, or gemcitabine permitted.
  3. Age > 18 years old
  4. Life expectancy >3 months
  5. Performance status 0-2 inclusive
  6. No more than mild to moderate hepatic impairment corresponding to Child-Pugh Class A or B, respectively (Child-Pugh score 5 to 9). See Appendix V for Child Pugh Classification.
  7. Women of child-bearing potential and men must agree to use adequate contraception such as abstinence or effective barrier and/or non-hormonal contraception for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  8. Adequate organ reserve to include: Absolute Neutrophil Count ≥ 1500/mcl , Hemoglobin ≥ 8.0 g/dl, platelet count ≥ 100,000/mcl, creatinine ≤ 2.0, AST & ALT ≤ 2.5 x ULN
  9. Baseline ECG showing QTc value ≤ 480 millisecond
  10. Informed consent

Exclusion Criteria:

  1. Use of any other concomitant chemotherapy agent concurrently with radiation therapy aside from capecitabine, gemcitabine, or 5-fluorouracil (none of these agents are CYP 3A4 substrates).
  2. Baseline vomiting is not controlled: Patients who have vomited or have nausea requiring antiemetic treatment within 24 hours prior to initiation of treatment.
  3. Scheduled to receive treatment within 24 hours prior to day one or during the study periods with other potential or known antiemetic agents including but not limited to serotonin antagonists aside from ondansetron per study protocol, phenothiazines, butyrophenones, substituted benzamides, antihistamines, and cannabinoids. Chronically used benzodiazepines may be continued as a single nightly dose for sleep.
  4. Any steroid use except topical steroids. Patients need to be off systemic steroid treatment for 7 days prior to start of chemoradiation therapy.
  5. Uncontrolled CNS tumor
  6. Other physical causes for nausea or vomiting (such as bowel obstruction) not related to chemoradiation administration
  7. Hypersensitivity to either of the study agents
  8. Planned simultaneous administration of any other investigational agents
  9. Pregnant or nursing women
  10. Patients taking other CYP3A4 inducers or inhibitors would be required to discontinue their use for at least 7 days prior to initiation of chemoradiation therapy. Examples of CYP3A4 inducers include aminoglutethimide, carbamazepine, nafcillin, nevirapine, phenobarbital, phenytoin, rifampin, and St. Johns Wort. Examples of CYP3A4 inhibitors include azole antifungals, clarithromycin, diclofenac, doxycycline, erythromycin, imatinib, isoniazid, nefazodone, nicardipine, propofol, protease inhibitors, quinidine, telithromycin, and verapamil.
  11. CYP3A4 substrates are not contraindicated. However, patients taking CYP3A4 substrates should be cautioned to consult with their physician to minimize their use, if possible. Example substrates include benzodiazepines, calcium channel blockers, ranolazine, ergot derivatives, mirtazapine, nateglinide, tacrolimus, and venlafaxine.
  12. Concomitant use of pimozide, terfenadine, cisapride, and astemizole is contraindicated per the Emend™ [10] product circular as dose-dependent inhibition of CYP 3A4 by aprepitant could result in elevated plasma concentrations of these drugs, potentially causing serious and life-threatening reactions. Patients taking these medications ineligible to participate in this study unless they are discontinued for at least 7 days prior to start of aprepitant.
  13. Warfarin: Aprepitant may increase warfarin metabolism and the INR may be decreased. Twice weekly monitoring of INR recommended in the first 2-week period of radiation followed by weekly monitoring in subsequent weeks until discontinuation of aprepitant. Twice weekly monitoring is again recommended after aprepitant discontinuation until INR has stabilized.
  14. Contraceptives (estrogens and progestins): Aprepitant may decrease the plasma levels of estrogen and progestin contraceptives. Contraceptive efficacy may be reduced. A nonhormonal form of contraception is necessary during treatment and for 1 month following the last dose of aprepitant.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00970905

Contacts
Contact: Steven Ades, MD MSc 802-656-5487 steven.ades@uvm.edu
Contact: Steven Grunberg, MD 802-656-5487 steven.grunberg@uvm.edu

Locations
United States, Arizona
Mayo Clinic Arizona Recruiting
Scottsdale, Arizona, United States, 85259-5499
Contact: Clinical Trials Referral Office    507-538-7623      
Principal Investigator: Michele Y Halyard, MD         
United States, North Carolina
Wake Forest Baptist Health Recruiting
Winston-Salem, North Carolina, United States, 27157
Contact: Margaret Crowley    336-713-6627    mcrowley@wakehealth.edu   
Principal Investigator: Arthur W Blackstock, MD         
United States, Vermont
Fletcher Allen Health Care Recruiting
Burlington, Vermont, United States, 05401
Contact: Karen Wilson    802-656-4101    karen.wilson@uvm.edu   
Contact: Kimberly Luebbers    802-656-2137    kimberly.luebbers@uvm.edu   
Principal Investigator: Steven Ades, MD MSc         
Sub-Investigator: Steven Grunberg, MD         
Sub-Investigator: Ruth Heimann, MD PhD         
Sub-Investigator: Marc Greenblatt, MD PhD         
Sponsors and Collaborators
University of Vermont
Mayo Clinic
Comprehensive Cancer Center of Wake Forest University
Norris Cotton Cancer Center
University of Massachusetts, Worcester
Investigators
Principal Investigator: Steven Ades, MD MSc University of Vermont
  More Information

No publications provided

Responsible Party: Steven Ades, Assistant Professor of Medicine, University of Vermont
ClinicalTrials.gov Identifier: NCT00970905     History of Changes
Other Study ID Numbers: VCC 0908
Study First Received: August 25, 2009
Last Updated: December 12, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Vermont:
Radiation
Nausea
Vomiting
Ondansetron
Aprepitant

Additional relevant MeSH terms:
Nausea
Vomiting
Ondansetron
Aprepitant
Signs and Symptoms, Digestive
Signs and Symptoms
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Gastrointestinal Agents
Antipruritics
Dermatologic Agents
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Anti-Anxiety Agents

ClinicalTrials.gov processed this record on July 20, 2014