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

NCT ID: NCT00970905

Last Updated: 2017-12-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-10-31
• Study Completion Date: 2016-08-01

Brief Summary

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.

Conditions

Nausea; Vomiting

Keywords

Radiation; Nausea; Vomiting; Ondansetron; Aprepitant

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Aprepitant & Ondansetron

Group Type: EXPERIMENTAL

aprepitant

Intervention Type: DRUG

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.

Ondansetron

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Emend; Zofran

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mayo Clinic

OTHER

Sponsor Role: collaborator

Wake Forest University Health Sciences

OTHER

Sponsor Role: collaborator

Norris Cotton Cancer Center

OTHER

Sponsor Role: collaborator

University of Massachusetts, Worcester

OTHER

Sponsor Role: collaborator

University of Vermont

OTHER

Sponsor Role: lead

Responsible Party

Steven Ades

Assistant Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Steven Ades, MD MSc

Role: PRINCIPAL_INVESTIGATOR

University of Vermont

Locations

Mayo Clinic Arizona

Scottsdale, Arizona, United States

Wake Forest Baptist Health

Winston-Salem, North Carolina, United States

Fletcher Allen Health Care

Burlington, Vermont, United States

Countries

United States

References

Ades S, Halyard M, Wilson K, Ashikaga T, Heimann R, Kumar S, Blackstock W. Effectiveness of aprepitant in addition to ondansetron in the prevention of nausea and vomiting caused by fractionated radiotherapy to the upper abdomen (AVERT). Support Care Cancer. 2017 May;25(5):1503-1510. doi: 10.1007/s00520-016-3540-4. Epub 2016 Dec 28.

Reference Type: DERIVED

PMID: 28032216 (View on PubMed)

Other Identifiers

VCC 0908

Identifier Type: -

Identifier Source: org_study_id