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

• Percentage of Patients With no Emesis and no Rescue Therapy During Repeated Courses of Chemotherapy [ Time Frame: Duration of time that the patient is on study ] [ Designated as safety issue: No ]
• Effects of Aprepitant on Nausea, Appetite, Taste Changes, (Via Visual Analogue Scale [VAS]), Nutritional Intake, and Mucositis in the Colorectal Cancer (CRC) Population. [ Time Frame: Duration of time the patient is on study ] [ Designated as safety issue: No ]
• To Assess the Safety of the Combination of Aprepitant, Palonosetron, and Dexamethasone in the Colorectal Cancer(CRC) Population in the First and Subsequent Cycles of Chemotherapy. [ Time Frame: Duration of time patient is on study ] [ Designated as safety issue: Yes ]
• Percentage of Patients With no Emesis and no Rescue Therapy Within 5 Days of the First Course of Chemotherapy [ Time Frame: within 5 days of chemotherapy ] [ Designated as safety issue: No ]

RATIONALE: Aprepitant, palonosetron, and dexamethasone may help lessen or prevent nausea and vomiting in patients receiving chemotherapy.

PURPOSE: This phase II trial is studying how well giving aprepitant together with palonosetron and dexamethasone works in preventing nausea and vomiting caused by chemotherapy in patients receiving chemotherapy for metastatic colorectal cancer.

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.

• Colorectal Cancer
• Nausea and Vomiting

• Drug: aprepitant
  Aprepitant 125 mg by mouth (PO) on day 1 and 80 mg PO on days 2 and 3 of each chemotherapy cycle
  Other Names:

  • Emend
  • MK-869
  • L-758,298
  • L-754,030
• Drug: dexamethasone
  Dexamethasone 12 mg PO on 1st day of study drug and 8 mg PO on days 2-4
• Drug: fluorouracil
  as per institutional standard of care
  Other Name: 5-FU
• Drug: irinotecan hydrochloride
  as per institutional standard of care
  Other Names:

  • Trade names: Camptosar®
  • Other names: Camptothecin-11, CPT-11
• Drug: leucovorin calcium
  as per institutional standard of care
  Other Names:

  • Generic Name: Leucovorin
  • Other Names: Citrovorum Factor, Folinic Acid
• Drug: oxaliplatin
  as per institutional standard of care
  Other Name: Trade Name: Eloxatin
• Drug: palonosetron hydrochloride
  Palonosetron 0.25 mg IV push on day 1 only.
  Other Name: Aloxi
• Procedure: quality-of-life assessment
  baseline

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