Phase II Trial Evaluating the Efficacy and Tolerability of Aprepitant & Palonosetron for Prevention of Chemotherapy-Induced Nausea and Vomiting

OBJECTIVES:

Primary

- Evaluate the efficacy, in terms of nausea and vomiting control, of aprepitant,
palonosetron hydrochloride, and dexamethasone, in preventing chemotherapy-induced
nausea and vomiting in patients receiving FOLFOX or FOLFIRI chemotherapy for metastatic
colorectal cancer.

Secondary

- Assess the percentage of patients with no emesis and no rescue therapy when treated
with aprepitant, palonosetron hydrochloride, and dexamethasone during repeated courses
of FOLFOX or FOLFIRI chemotherapy.

- Assess the effects of aprepitant on nausea, appetite, taste changes (via visual
analogue scale), nutritional intake, and mucositis in these patients.

- Assess the safety of this regimen in these patients.

OUTLINE: This is an open-label, multicenter study.

Beginning 1 hour prior to the initiation of chemotherapy on day 1, patients receive oral
aprepitant on days 1-3, oral dexamethasone on days 1-4, and palonosetron hydrochloride IV on
day 1.

Nausea is assessed daily for up to 4 courses of chemotherapy.

Quality of life is assessed at baseline.

PROJECTED ACCRUAL: A total of 100 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

- Diagnosis of colorectal cancer

- Metastatic disease

- Scheduled to receive 1 of the following chemotherapy regimens*:

- FOLFOX 4 (oxaliplatin, fluorouracil, leucovorin calcium)

- FOLFOX 6

- FOLFOX 7

- FOLFIRI (irinotecan hydrochloride, fluorouracil, leucovorin calcium) NOTE:
*Regimens may also include cetuximab or bevacizumab

- No emesis and no requirement for antiemetic agents within 48 hours prior to beginning
chemotherapy

- Single-agent benzodiazepines as a hypnotic allowed

- No chronic nausea

PATIENT CHARACTERISTICS:

- Eastern Cooperative Oncology Group (ECOG) performance status 0-2

- Life expectancy > 4 months

- White Blood Cell(WBC)count > 3,000/mm^³

- Absolute neutrophil count (ANC) > 1,500/mm^³

- Platelet count > 100,000/mm^³

- Bilirubin ≤ 2.5 times upper limit of normal (ULN) (< 5 times ULN if liver metastases
present)

- Creatinine ≤ 1.5 times ULN

- Aspartate aminotransferase(AST) or Alanine aminotransferase (ALT) ≤ 2.5 times ULN (<
5 times ULN if liver metastases present)

- Able to swallow tablets and capsules

- No known sensitivity to aprepitant, palonosetron hydrochloride, or dexamethasone

- Not pregnant or nursing

- Negative pregnancy test

- No history of consuming ≥ 5 alcoholic drinks/day within the past year

- No concurrent illness requiring systemic corticosteroids other than planned
dexamethasone during study treatment

- No clinical signs of active systemic infection involving the gastrointestinal tract

- No active bowel obstruction

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No prior chemotherapy > Hesketh level 3

- Prior fluorouracil with or without leucovorin calcium or capecitabine allowed

- At least 30 days since prior investigational drugs

- At least 14 days since prior neurokinin-1 antagonists

- Concurrent hydrocortisone at physiologic replacement doses (≤ 30 mg/day) allowed

- No concurrent chronic antiemetic agents

- Concurrent hypnotics allowed

- Concurrent rescue antiemetics allowed