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

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

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.

Study Overview

• Status: Completed
• Conditions: Ovarian Cancer; Uterine Cancer
• Intervention / Treatment: Drug: fosaprepitant; Other: Oral Placebo; Drug: aprepitant; Other: IV placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Newport Beach, California, United States, 92663
      • Gynecologic Oncology Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Fosaprepitant; 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; 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; Other Names: Emend IV; Other: Oral Placebo; One pill administered on days 1-3 in conjunction with Fosaprepitant.
Active Comparator: Aprepitant; 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; 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; Other Names: Emend; Other: IV placebo; 100 cc of IV placebo administered on day in conjunction with Aprepitant; Other Names: Normal Saline

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Gynecologic Oncology Associates
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: John P Micha, MD, Gynecologic Oncology Associates

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: September 7, 2011
• First Submitted That Met QC Criteria: September 8, 2011
• First Posted (Estimate): September 12, 2011

Study Record Updates

• Last Update Posted (Actual): March 28, 2017
• Last Update Submitted That Met QC Criteria: February 24, 2017
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: gynecologic cancer; emesis; aprepitant; fosaprepitant
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Female; Uterine Diseases; Signs and Symptoms, Digestive; Vomiting; Uterine Neoplasms; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Neurokinin-1 Receptor Antagonists; Aprepitant; Fosaprepitant
• Other Study ID Numbers: GOA-NVM1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO