Granisetron, Aprepitant, and Dexamethasone in Preventing Nausea and Vomiting in Patients Receiving Chemotherapy for Stage II, III, or IV Ovarian Cancer

PRIMARY OBJECTIVES:

I. To determine the frequency of chemotherapy-induced nausea and vomiting based on complete
response (no vomiting and no use of rescue therapy) during the 6 days following
intraperitoneal (IP) chemotherapy for the 3-day regimen of aprepitant (both injection and
capsules) in combination with granisetron transdermal system and dexamethasone in ovarian
cancer patients receiving IP cisplatin OR IP carboplatin.

SECONDARY OBJECTIVES:

I. To evaluate possible endpoints for the chemotherapy-induced nausea and vomiting,
including:

- Functional Living Index-Emesis (FLIE) questionnaire scores

- Mean vomiting, nausea and total FLIE scores and changes from baseline in FLIE scores

- Percentages of patients with no impact on daily living (NIDL), i.e. > 108/126 total FLIE
score II. To describe the timing of nausea and vomiting that may guide modifications to
the standard regimen.

OUTLINE: This is a multicenter study.

Patients apply one patch of granisetron transdermal system to the upper outer arm on day 0
(at least 24 hours before intraperitoneal [IP] platinum therapy). Patients then receive
dexamethasone orally (PO) on days 1-4, aprepitant IV over 15 minutes on day 1 (30 minutes
before IP platinum therapy), and aprepitant PO on days 2-3.

Patients complete the Functional Living Index--Emesis (FLIE) and a symptom diary at baseline
and on days 3 and 6.

Inclusion Criteria:

- Diagnosis of ovarian epithelial, fallopian tube, or primary peritoneal carcinoma

- Stage II, III, or IV disease with optimal (=< 1 cm residual disease) or
suboptimal residual disease

- All patients must have a procedure for determining diagnosis of epithelial
ovarian, fallopian tube, primary peritoneal, with appropriate tissue for
histologic evaluation

- The minimum surgery required is an abdominal surgery providing tissue for
histologic evaluation and establishing and documenting the primary site and
stage, as well as a maximal effort at tumor debulking; if additional surgery was
performed, it should have been in accordance with appropriate surgery for ovarian
or peritoneal carcinoma described in the Gynecologic Oncology Group (GOG)
Surgical Procedures Manual

- Patients with the following histologic epithelial cell types are eligible:

- Serous adenocarcinoma, endometrioid adenocarcinoma, mucinous adenocarcinoma,
undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial
carcinoma, transitional cell carcinoma, malignant Brenner's Tumor, or
adenocarcinoma not otherwise specified (N.O.S.)

- However, the histologic features of the tumor must be compatible with a primary
Müllerian epithelial adenocarcinoma; if doubt exists, it is recommended that the
investigator should have the slides reviewed by an independent pathologist prior
to entry

- Patients may have co-existing endometrial cancer so long as the primary origin of
invasive tumor is ovarian or peritoneal for clarification of synchronous primary
endometrial cancer

- Patients receiving the initial course of chemotherapy including

- Paclitaxel 135 mg/M2 IV over 3 hours on day 1 and

- Cisplatin 75 mg/M2 IP on day 2 OR

- Paclitaxel 80 mg/m2 IV days 1, 8 and 15 and

- Carboplatin AUC 6 IP on day 1

- Prothrombin time (PT) such that international normalized ratio (INR) is < 1.5 x ULN
(or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of
therapeutic warfarin)

- Partial thromboplastin time (PTT) < 1.5 times the upper limit of normal (heparin,
lovenox or alternative anticoagulants are acceptable)

- Patients with a GOG Performance Status of 0, 1, or 2

- Patients who are able to read, understand and write English; if FLIE which has been
translated into other languages, and validated, becomes available, then patients
speaking these languages can be enrolled if translation of the symptom diary can be
arranged dependent on availability of suitable translators

- Patients who are able to complete the assessments

- Patients who are able to comply with the anti-emetic therapy

- Patients must have met pre-entry requirements

- Patients must have signed an approved informed consent and authorization permitting
release of personal health information

Exclusion Criteria:

- Patients who are known to be hypersensitive to aprepitant, granisetron or any of the
components of the patch or to dexamethasone

- Patients who have received prior radiotherapy to any portion of the abdominal cavity
or pelvis are excluded; prior radiation for localized cancer of the breast, head and
neck, or skin is permitted, provided that it was completed more than three years prior
to registration, and the patient remains free of recurrent or metastatic disease

- Patients who have received prior chemotherapy for any abdominal or pelvic tumor
including neo-adjuvant chemotherapy for their ovarian or primary peritoneal cancer are
excluded; patients may have received prior adjuvant chemotherapy for localized breast
cancer, provided that it was completed more than three years prior to registration,
and that the patient remains free of recurrent or metastatic disease

- Patients who are pregnant or nursing; to date, no fetal studies in animals or humans
have been performed; the possibility of harm to a fetus is likely

- Patients with clinical symptoms or signs of gastrointestinal obstruction and/ or those
who require parenteral hydration and/or nutrition; patients with history or current
diagnosis of inflammatory bowel disease are not eligible

- Patients with medical history or conditions not otherwise previously specified which
in the opinion of the investigator should exclude participation in this study;
examples of this would be hearing loss or neuropathy which would prevent tolerance to
cisplatin, and paclitaxel administration; the investigator should feel free to consult
the Study Chair or Study Co-Chairs for uncertainty in this regard

- Patients who, in the opinion of the treating physician, have a medical condition, or
currently take medications, which are felt to contraindicate safe or effective
administration of the standard three drug anti-emetic regimen used in this study