Phase II Trial of Aprepitant & Palonosetron for CINV Prevention w FOLFOX

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Multi-Center, Trial to Evaluate the Efficacy & Tolerability of Aprepitant and Palonosetron for the Prevention of CINV in Colorectal Cancer (CRC) Patients Receiving FOLFOX

Conditions
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Colorectal Cancer, Nausea and Vomiting

Intervention / Treatment
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* Drug: aprepitant
* Drug: dexamethasone
* Drug: fluorouracil
* Drug: irinotecan hydrochloride
* Drug: leucovorin calcium
* Drug: oxaliplatin
* Drug: palonosetron hydrochloride
* Procedure: quality-of-life assessment


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aprepitant and Palonosetron<br> | Drug: aprepitant<br>* Aprepitant 125 mg by mouth (PO) on day 1 and 80 mg PO on days 2 and 3 of each chemotherapy cycle<br>* Other names: L-754,030;Drug: dexamethasone<br>* Dexamethasone 12 mg PO on 1st day of study drug and 8 mg PO on days 2-4<br>Drug: fluorouracil<br>* as per institutional standard of care<br>* Other names: 5-FU;Drug: irinotecan hydrochloride<br>* as per institutional standard of care<br>* Other names: Other names: Camptothecin-11, CPT-11;Drug: leucovorin calcium<br>* as per institutional standard of care<br>* Other names: Other Names: Citrovorum Factor, Folinic Acid;Drug: oxaliplatin<br>* as per institutional standard of care<br>* Other names: Trade Name: Eloxatin;Drug: palonosetron hydrochloride<br>* Palonosetron 0.25 mg IV push on day 1 only.<br>* Other names: Aloxi;Procedure: quality-of-life assessment<br>* baseline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With no Emesis and no Rescue Therapy Within 5 Days of Receiving FOLFOX and FOLFIRI in the First Cycle of Chemotherapy. |  | Up to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With no Emesis and no Rescue Therapy During Repeated Courses of Chemotherapy |  | Duration of time that the patient is on study | 
| Effects of Aprepitant on Nausea, Appetite, Taste Changes, (Via Visual Analogue Scale [VAS]), Nutritional Intake, and Mucositis in the Colorectal Cancer (CRC) Population. |  | Duration of time the patient is on study | 
| 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. |  | Duration of time patient is on study | 
| Percentage of Patients With no Emesis and no Rescue Therapy Within 5 Days of the First Course of Chemotherapy |  | within 5 days of chemotherapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nausea and vomiting, recurrent colon cancer, stage IV colon cancer, recurrent rectal cancer, stage IV rectal cancer