Effectiveness of Aprepitant in Addition to Ondansetron in the Prevention of Nausea and Vomiting Caused by Upper Abdominal Radiotherapy
Information source: University of Vermont
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Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Nausea; Vomiting
Intervention: aprepitant (Drug); Ondansetron (Drug)
Phase: Phase 2
Sponsored by: University of Vermont
Official(s) and/or principal investigator(s):
Steven Ades, MD MSc, Principal Investigator, Affiliation: University of Vermont
Steven Ades, MD MSc, Phone: 802-656-5487, Email: firstname.lastname@example.org
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.
Official title: Effectiveness of Aprepitant in Addition to Ondansetron in the Prevention of Nausea and Vomiting Caused by Fractionated Radiotherapy to the Upper Abdomen
Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Complete Response rate (no vomiting and no rescue anti-emetic therapy)
Complete Response rate
Proportion of patients who did not vomit
No Significant Nausea: The proportion of patients who did not experience any nausea ≥ 3 on 0 - 10 scale
No Nausea: The proportion of patients who did not experience any nausea. Nausea = 0 on 0 - 10 scale
Complete Protection: The proportion of patients who did not vomit, require rescue therapy, or have nausea ≥ 3 on 0 - 10 scale
Total Protection: The proportion of patients who did not vomit, require rescue therapy, or have any nausea (Nausea = 0 on 0 - 10 scale).
Vomiting frequency: The frequency of vomiting (# episodes per week) in patients who did vomit at least once.
Nausea frequency: The frequency of nausea (Nausea > 0 in a given week/ number of weeks during overall period of radiation treatment)
Significant Nausea frequency: The frequency of significant nausea (Nausea ≥ 3 in a given week/ number of weeks during overall period of radiation treatment)
Frequency of rescue medication use: The number of days in which rescue medication was taken / number of days of radiotherapy
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.
All adverse events that occur during radiation treatment with assessment of severity (CTC v.3) and relationship to study drug.
Minimum age: 18 Years.
Maximum age: N/A.
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
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
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
9. Baseline ECG showing QTc value ≤ 480 millisecond
10. Informed consent
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
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™  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.
Locations and Contacts
Steven Ades, MD MSc, Phone: 802-656-5487, Email: email@example.com
Mayo Clinic Arizona, Scottsdale, Arizona 85259-5499, United States; Recruiting
Clinical Trials Referral Office, Phone: 507-538-7623
Michele Y Halyard, MD, Principal Investigator
Wake Forest Baptist Health, Winston-Salem, North Carolina 27157, United States; Recruiting
Margaret Crowley, Phone: 336-713-6627, Email: firstname.lastname@example.org
Arthur W Blackstock, MD, Principal Investigator
Fletcher Allen Health Care, Burlington, Vermont 05401, United States; Recruiting
Karen Wilson, Phone: 802-656-4101, Email: email@example.com
Kimberly Luebbers, Phone: 802-656-2137, Email: firstname.lastname@example.org
Steven Ades, MD MSc, Principal Investigator
Steven Grunberg, MD, Sub-Investigator
Ruth Heimann, MD PhD, Sub-Investigator
Marc Greenblatt, MD PhD, Sub-Investigator
Starting date: October 2009
Last updated: December 12, 2013