Fosaprepitant Versus Aprepitant in the Prevention of Chemotherapy Induced Nausea and Vomiting

Study Overview
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Brief Summary
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Nausea and vomiting are two of the more concerning adverse outcomes associated with chemotherapy in the treatment of gynecologic malignancies. In fact, nearly 90% of cancer patients develop chemotherapy induced nausea and vomiting (CINV) following treatment with carboplatin and paclitaxel. The successful control of chemotherapy induced nausea and vomiting (CINV) is thus, of paramount importance in ensuring optimal treatment and sustaining a cancer patient's quality of life.

Detailed Description
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Studies have indicated that oral and intravenous anti-emetics are equivalent with regard to efficacy; when evaluating cost and convenience, the intravenous route may be preferable. Fosaprepitant, a water-soluble phosphoryl prodrug for aprepitant, is converted to aprepitant via phosphatases following intravenous administration. Given the rapid conversion of fosaprepitant to the active form (i.e., aprepitant), the two medications appear to provide a similarly effective antiemetic impact. Clinical reports have additionally suggested that fosaprepitant could be appropriate as an intravenous alternative to the oral aprepitant.

Official Title
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A Phase IV Study Comparing the Efficacy of Fosaprepitant to Aprepitant for Chemotherapy Induced Nausea and Vomiting in Patients Treated for Gynecological Cancer

Conditions
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Ovarian Cancer, Uterine Cancer

Intervention / Treatment
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* Drug: fosaprepitant
* Drug: aprepitant
* Other: Oral Placebo
* Other: IV placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female Gender Age > 18 years A histologic diagnosis of stage III/IV gynecologic cancer (e.g., epithelial ovarian, fallopian tube, peritoneal cancer and uterine cancer). Subjects who will be treated with Taxol and Carboplatin as standard of care for a newly diagnosed gynecological cancer. Adequate bone marrow function as demonstrated by: Absolute neutrophil count (ANC) > 1,500/μL; platelet count > 100,000/μL; and hemoglobin > 9 g/dL • Adequate renal function demonstrated by: Serum creatinine of < 1.5 x ULN or 24-hr measured urine creatinine clearance > 60 mL/min for patients with serum creatinine > 1.5 x ULN • Adequate hepatic function demonstrated by: Total bilirubin of < 1.5 x ULN AST or ALT ≤ 2.5 x ULN EGOG status of < 2: Postoperatively, patients demonstrate an ECOG score of 1 or 2. However, during the first cycle of chemotherapy, the patients' performance status improves to < 1. Projected life expectancy of at least 3 months Ability to comply with the visit schedule and assessments required by the protocol Negative pregnancy test for women of childbearing potential Signed, IRB approved informed consent and HIPPA consent Exclusion Criteria: Subjects with a diagnosis of epithelial ovarian, fallopian tube or peritoneal cancers of low malignant potential (borderline carcinomas) are not eligible. Allergy or intolerance to 5HT3 or NK-1 antagonists and dexamethasone An episode of vomiting or retching within 24 hours before the start of the initial treatment with chemotherapy Subjects with concomitant malignancy or a previous malignancy within the past three (3) years (except non-melanoma skin cancer) Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study. Screening clinical laboratory values of: ANC of <1500/DL Platelet count of <100,000/µL Total bilirubin of *1.5 mg/dL x ULN SGOT (AST) or SGPT (ALT) * 2.5 x ULN Serum creatinine of * 1.5 mg/dL Hemoglobin of * 9 gm/dL (may be transfused or receive a colony stimulating factor to maintain or exceed this level) EGOG status of > 2 Gastrointestinal obstruction or an active peptic ulcer Patients who are pregnant or breast feeding because aprepitant may be harmful to the developing fetus and newborn Known active HIV and viral hepatitis infections Inability to comply with study New York Heart Association (NYHA) Grade II or greater congestive heart failure (see Appendix D)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Fosaprepitant<br>Fosaprepitant for Injection 150 mg is administered intravenously on Day 1 only as an infusion over 20-30 minutes initiated approximately 30 minutes prior to chemotherapy. Oral Placebo given on days 1-3 | Drug: fosaprepitant<br>* Fosaprepitant for Injection 150 mg is administered intravenously on Day 1 only as an infusion over 20-30 minutes initiated approximately 30 minutes prior to chemotherapy. Patient will receive standard pre-medications<br>* Other names: Emend IV;Other: Oral Placebo<br>* One pill administered on days 1-3 in conjunction with Fosaprepitant.<br>|
| Active Comparator: Aprepitant<br>Aprepitant 125 mg orally 1 hour prior to chemotherapy treatment (Day 1) and 80 mg orally once daily in the morning on Days 2 and 3. 100 cc of IV placebo administered on day 1 | Drug: aprepitant<br>* Aprepitant 125 mg orally 1 hour prior to chemotherapy treatment (Day 1) and 80 mg orally once daily in the morning on Days 2 and 3. patient will receive standard pre-medications<br>* Other names: Emend;Other: IV placebo<br>* 100 cc of IV placebo administered on day in conjunction with Aprepitant<br>* Other names: Normal Saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Complete Response Rate | no emetic episodes or rescue therapy following the initiation of chemotherapy | 13 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impact on Daily Living Activities | Proportion of patients reporting no impact on daily living activities following initiation of chemotherapy | 13 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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aprepitant, fosaprepitant, gynecologic cancer, emesis