- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00970905
Effectiveness of Aprepitant in Addition to Ondansetron in the Prevention of Nausea and Vomiting Caused by Upper Abdominal Radiotherapy (AVERT)
December 2, 2017 updated by: Steven Ades, University of Vermont
Effectiveness of Aprepitant in Addition to Ondansetron in the Prevention of Nausea and Vomiting Caused by Fractionated Radiotherapy to the Upper Abdomen
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.
Study Overview
Status
Completed
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
52
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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Arizona
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Scottsdale, Arizona, United States, 85259-5499
- Mayo Clinic Arizona
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North Carolina
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Winston-Salem, North Carolina, United States, 27157
- Wake Forest Baptist Health
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Vermont
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Burlington, Vermont, United States, 05401
- Fletcher Allen Health Care
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Any patient with a diagnosis of malignancy localized to the upper abdomen and requiring chemoradiation or radiation alone.
- 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.
- Age > 18 years old
- Life expectancy >3 months
- Performance status 0-2 inclusive
- 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.
- 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.
- 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
- Baseline ECG showing QTc value ≤ 480 millisecond
- Informed consent
Exclusion Criteria:
- 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).
- Baseline vomiting is not controlled: Patients who have vomited or have nausea requiring antiemetic treatment within 24 hours prior to initiation of treatment.
- 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.
- Any steroid use except topical steroids. Patients need to be off systemic steroid treatment for 7 days prior to start of chemoradiation therapy.
- Uncontrolled CNS tumor
- Other physical causes for nausea or vomiting (such as bowel obstruction) not related to chemoradiation administration
- Hypersensitivity to either of the study agents
- Planned simultaneous administration of any other investigational agents
- Pregnant or nursing women
- 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.
- 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.
- 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.
- 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.
- 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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Aprepitant & Ondansetron
|
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 Names:
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 Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Complete Response rate (no vomiting and no rescue anti-emetic therapy)
Time Frame: overall period of radiation treatment (4-8 weeks)
|
overall period of radiation treatment (4-8 weeks)
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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)
|
Cumulatively increasing time intervals from the start of radiation therapy (7 days, 14 days, 21 days, 28 days, 35 days, 42 days)
|
Proportion of patients who did not vomit
Time Frame: Overall period of radiation therapy (4-8 weeks)
|
Overall period of radiation therapy (4-8 weeks)
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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)
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Overall period of radiation treatment (4-8 weeks)
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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)
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Overall period of radiation treatment (4-8 weeks)
|
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)
|
Overall period of radiation treatment (4-8 weeks)
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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)
|
Overall period of radiation treatment (4-8 weeks)
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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)
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Overall period of radiation treatment (4-8 weeks)
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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)
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Overall period of radiation treatment (4-8 weeks)
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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)
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Overall period of radiation treatment (4-8 weeks)
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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)
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overall period of radiation treatment (4-8 weeks)
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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)
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Overall period of radiation treatment (4-8 weeks)
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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)
|
Overall period of radiation treatment (4-8 weeks)
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Steven Ades, MD MSc, University of Vermont
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
October 1, 2009
Primary Completion (Actual)
July 1, 2016
Study Completion (Actual)
August 1, 2016
Study Registration Dates
First Submitted
August 25, 2009
First Submitted That Met QC Criteria
September 2, 2009
First Posted (Estimate)
September 3, 2009
Study Record Updates
Last Update Posted (Actual)
December 5, 2017
Last Update Submitted That Met QC Criteria
December 2, 2017
Last Verified
December 1, 2017
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Signs and Symptoms, Digestive
- Nausea
- Vomiting
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Autonomic Agents
- Peripheral Nervous System Agents
- Antiemetics
- Gastrointestinal Agents
- Dermatologic Agents
- Antipsychotic Agents
- Tranquilizing Agents
- Psychotropic Drugs
- Serotonin Agents
- Serotonin Antagonists
- Anti-Anxiety Agents
- Antipruritics
- Neurokinin-1 Receptor Antagonists
- Ondansetron
- Aprepitant
Other Study ID Numbers
- VCC 0908
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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