Colorectal Cancer, Nausea and Vomiting
Conditions
Keywords
nausea and vomiting, recurrent colon cancer, stage IV colon cancer, recurrent rectal cancer, stage IV rectal cancer
Brief summary
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
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.
Interventions
DRUGaprepitant
Aprepitant 125 mg by mouth (PO) on day 1 and 80 mg PO on days 2 and 3 of each chemotherapy cycle
DRUGdexamethasone
Dexamethasone 12 mg PO on 1st day of study drug and 8 mg PO on days 2-4
DRUGfluorouracil
as per institutional standard of care
DRUGirinotecan hydrochloride
as per institutional standard of care
DRUGleucovorin calcium
as per institutional standard of care
DRUGoxaliplatin
as per institutional standard of care
Palonosetron 0.25 mg IV push on day 1 only.
PROCEDUREquality-of-life assessment
baseline
Sponsors
National Cancer Institute (NCI)
OHSU Knight Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | 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
| Measure | 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Aprepitant and Palonosetron Aprepitant: 125 mg by mouth (PO) on day 1 and 80 mg PO on days 2 and 3 of each chemotherapy cycle
Palonosetron: 0.25 mg IV push on day 1 only | 54 |
| Total | 54 |
Baseline characteristics
| Characteristic | Aprepitant and Palonosetron |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 12 Participants |
| Age, Categorical Between 18 and 65 years | 42 Participants |
| Age, Continuous | 55 years STANDARD_DEVIATION 11.728 |
| Region of Enrollment United States | 54 participants |
| Sex: Female, Male Female | 24 Participants |
| Sex: Female, Male Male | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 18 / 54 |
| serious Total, serious adverse events | 29 / 54 |
Outcome results
Primary
Number of Participants With no Emesis and no Rescue Therapy Within 5 Days of Receiving FOLFOX and FOLFIRI in the First Cycle of Chemotherapy.
Time frame: Up to 24 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aprepitant and Palonosetron | Number of Participants With no Emesis and no Rescue Therapy Within 5 Days of Receiving FOLFOX and FOLFIRI in the First Cycle of Chemotherapy. | 54 Participants |
Secondary
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
Secondary
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
Secondary
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
Secondary
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