Ovarian Cancer, Uterine Cancer
Conditions
Keywords
aprepitant, fosaprepitant, gynecologic cancer, emesis
Brief summary
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
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.
Interventions
DRUGfosaprepitant
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
DRUGaprepitant
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
OTHEROral Placebo
One pill administered on days 1-3 in conjunction with Fosaprepitant.
OTHERIV placebo
100 cc of IV placebo administered on day in conjunction with Aprepitant
Sponsors
Merck Sharp & Dohme LLC
Gynecologic Oncology Associates
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Complete Response Rate | 13 months | no emetic episodes or rescue therapy following the initiation of chemotherapy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Impact on Daily Living Activities | 13 months | Proportion of patients reporting no impact on daily living activities following initiation of chemotherapy |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fosaprepitant Including Placebo Fosaprepitant (EMEND™) 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 125 mg given 1 hour prior to infusion of chemotherapy on day 1 and oral Placebo 80 mg on day 2 and day 3.Patient will receive standard pre-medications on day 1
Aprepitant (EMEND™) is 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
fosaprepitant including placebo: 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 | 10 |
| Aprepitant Including Placebo Aprepitant (EMEND™) is 125 mg orally 1 hour prior to chemotherapy treatment (Day 1) with Intravenous Placebo and 80 mg orally once daily in the morning on Days 2 and 3 with Placebo Intravenously on day 1. patient will receive standard pre-medications on day 1.
aprepitant including placebo: 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 | 10 |
| Total | 20 |
Baseline characteristics
| Characteristic | Fosaprepitant Including Placebo | Aprepitant Including Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 1 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants | 9 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 10 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 10 participants | 10 participants | 20 participants |
| Sex/Gender, Customized Female | 10 participants | 10 participants | 20 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 10 | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 |
Outcome results
Primary
Overall Complete Response Rate
no emetic episodes or rescue therapy following the initiation of chemotherapy
Time frame: 13 months
Population: Study participants included adult, female patients with a histologically confirmed, newly diagnosed gynecologic cancer (e.g., epithelial ovarian, fallopian tube, primary peritoneal cancer or uterine cancer).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fosaprepitant Including Placebo | Overall Complete Response Rate | 10 percentage of participants |
| Aprepitant Including Placebo | Overall Complete Response Rate | 10 percentage of participants |
Secondary
Impact on Daily Living Activities
Proportion of patients reporting no impact on daily living activities following initiation of chemotherapy
Time frame: 13 months
Population: Study participants included adult, female patients with a histologically confirmed, newly diagnosed gynecologic cancer (e.g., epithelial ovarian, fallopian tube, primary peritoneal cancer or uterine cancer).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fosaprepitant Including Placebo | Impact on Daily Living Activities | 10 percentage of participants |
| Aprepitant Including Placebo | Impact on Daily Living Activities | 10 percentage of participants |