Extrahepatic Bile Duct Cancer, Nausea, Vomiting, Stage II Pancreatic Cancer, Stage III Pancreatic Cancer, Stage IV Pancreatic Cancer
Conditions
Brief summary
This pilot clinical trial is studying how well aprepitant works in preventing nausea and vomiting in patients undergoing chemotherapy and radiation therapy for pancreatic cancer. Antiemetic drugs, such as aprepitant may help lessen or prevent nausea and vomiting in patients receiving chemotherapy and radiation therapy
Detailed description
PRIMARY OBJECTIVES: I. Discern the gastrointestinal toxicities associated with 5-FU (fluorouracil)/Gemcitabine (gemcitabine hydrochloride) chemotherapy when combined with upper abdominal radiation therapy. II. Determine if the addition of prophylactic Aprepitant/5HT-3/Dexamethasone therapy to standard chemoradiation for patients with pancreatic cancer results in less nausea and vomiting when compared to historical controls. SECONDARY OBJECTIVES: I. To determine the impact of prophylactic Aprepitant/5HT-3/Dexamethasone therapy on the impact of emesis on daily living, as measured using the MASCC Antiemesis (MAT) tool. OUTLINE: CHEMORADIOTHERAPY: Patients undergo radiation therapy once daily on days 1-5 for 5.5 weeks. Patients also receive gemcitabine hydrochloride intravenously (IV) over 30 minutes once weekly and either fluorouracil IV continuously or capecitabine orally (PO) twice daily on days 1-5. PROPHYLACTIC THERAPY: Beginning 1 hour before chemoradiotherapy, patients receive aprepitant PO on days 1-3. Treatment repeats every 7 days for 5.5 weeks in the absence of disease progression or unacceptable toxicity. CONSOLIDATION CHEMOTHERAPY: Two to four weeks after completion of chemoradiotherapy and prophylactic therapy, patients without disease progression or a declining performance status receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically.
Interventions
PROCEDUREquality-of-life assessment
Ancillary studies
DRUGaprepitant
Given PO
DRUGgemcitabine hydrochloride
Given IV
DRUGcapecitabine
Given PO
DRUGfluorouracil
Given IV
PROCEDUREradiation therapy
Undergo radiation therapy
OTHERquestionnaire administration
Ancillary studies
PROCEDUREnausea and vomiting therapy
Receive aprepitant
PROCEDUREmanagement of therapy complications
Receive aprepitant
Sponsors
National Cancer Institute (NCI)
Merck Sharp & Dohme LLC
Wake Forest University Health Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologic or cytologic diagnosis of carcinoma arising from the pancreas * Resected or unresectable pancreatic cancer, potentially resectable, or resectable (neoadjuvant) disease (stage II and III); stage IV patients with symptomatic back pain requiring palliation are also eligible at the discretion of the Principal Investigator (PI); resected patients, i.e. - Whipple of biliary ductal cancers are also eligible at the discretion of the PI * Performance status 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale * Evidence of disease; this can be measurable, evaluable, or nonmeasurable * Estimated life expectancy of at least 12 weeks * Absolute neutrophil (segmented and bands) count (ANC) \>= 1.5 X 10\^9/L * Platelets \>= 100 X 10\^9/L * Hemoglobin \>= 9 g/dL * Bilirubin =\< 1.5 times upper limit of normal (ULN) * Alkaline phosphatase (AP) =\< 3.0 ULN ( AP =\< 5 x ULN is acceptable if liver has tumor involvement) * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 3.0 ULN (AST and ALT =\< 5 x ULN is acceptable if liver has tumor involvement) * Albumin \>= 3.0 g/dL * Signed informed consent from patient * Male and female patients with reproductive potential must use an approved contraceptive method (e.g., intrauterine device, birth control pills, or barrier device) during and for 3 months after the study
Exclusion criteria
* Active infection (at the discretion of the investigator) * Neuroendocrine tumor of the pancreas * Documented brain metastasis; brain imaging in symptomatic patients is required to rule out metastases, but not required in asymptomatic patients * Pregnancy * Breast feeding * Serious concomitant systemic disorders incompatible with the study (at the discretion of the investigator) * Use of any investigational agent within 4 weeks before enrollment into the study * Significant cardiovascular disease in the form of abnormal electrocardiogram (ECG) coupled with clinical features of recent or recurrent cardiac disease (including myocardial infarction, angina or hypertension) * Prior treatment with chemotherapy for pancreatic cancer * Clinically significant effusions (pleural or peritoneal) that cannot be drained
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Gastrointestinal Toxicities (Grade 3 and 4 Nausea and Vomiting) Associated With Delivering Fluorouracil/Gemcitabine Hydrochloride-based Chemotherapy With Upper Abdominal Radiation | Over 10 weeks | Toxicity will be determined using the revised National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 3.0 for Toxicity and Adverse Event Reporting. Descriptive statistics (means, standard deviations, frequencies, etc.) will be presented for pretreatment patient characteristics. The rate of grade 3 and 4 nausea will be compared to the cut points during interim and final analyses. |
Secondary
| Measure | Time frame |
|---|---|
| Impact of Aprepitant/5HT-3 Antagonist Therapy on the Patient Quality of Life as Measured by the Number of Patients Using Anti Nausea Drugs | Week 1 |
| Impact of Aprepitant/5HT-3 Antagonist Therapy on the Patient Quality of Life as Measured by the Number of Patients Taking Anti Nausea Drugs | Week 5 |
Countries
United States
Participant flow
Recruitment details
The study began recruiting patients 08/31/2006 and closed to enrollment 12/03/2009. Patients were recruited from the Comprehensive Cancer Center of Wake Forest Baptist Health.
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Antiemetic, Chemotherapy, and Radiation Therapy) CHEMORADIOTHERAPY: Patients undergo radiation therapy once daily on days 1-5 for 5.5 weeks. Patients also receive gemcitabine hydrochloride IV over 30 minutes once weekly and either fluorouracil IV continuously or capecitabine PO twice daily on days 1-5.
PROPHYLACTIC THERAPY: Beginning 1 hour before chemoradiotherapy, patients receive aprepitant PO on days 1-3. Treatment repeats every 7 days for 5.5 weeks in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION CHEMOTHERAPY: Two to four weeks after completion of chemoradiotherapy and prophylactic therapy, patients without disease progression or a declining performance status receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Lack of Efficacy | 3 |
| Overall Study | Liver Mets before treatment | 1 |
| Overall Study | Physician Decision | 3 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Treatment (Antiemetic, Chemotherapy, and Radiation Therapy) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 7 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants |
| Age, Continuous | 62.4 years STANDARD_DEVIATION 11.4 |
| Region of Enrollment United States | 20 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 5 / 21 |
| serious Total, serious adverse events | 4 / 21 |
Outcome results
Primary
Number of Patients With Gastrointestinal Toxicities (Grade 3 and 4 Nausea and Vomiting) Associated With Delivering Fluorouracil/Gemcitabine Hydrochloride-based Chemotherapy With Upper Abdominal Radiation
Toxicity will be determined using the revised National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 3.0 for Toxicity and Adverse Event Reporting. Descriptive statistics (means, standard deviations, frequencies, etc.) will be presented for pretreatment patient characteristics. The rate of grade 3 and 4 nausea will be compared to the cut points during interim and final analyses.
Time frame: Over 10 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Antiemetic, Chemotherapy, and Radiation Therapy) | Number of Patients With Gastrointestinal Toxicities (Grade 3 and 4 Nausea and Vomiting) Associated With Delivering Fluorouracil/Gemcitabine Hydrochloride-based Chemotherapy With Upper Abdominal Radiation | 3 participants |
Secondary
Impact of Aprepitant/5HT-3 Antagonist Therapy on the Patient Quality of Life as Measured by the Number of Patients Taking Anti Nausea Drugs
Time frame: Week 5
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Antiemetic, Chemotherapy, and Radiation Therapy) | Impact of Aprepitant/5HT-3 Antagonist Therapy on the Patient Quality of Life as Measured by the Number of Patients Taking Anti Nausea Drugs | 5 participants |
Secondary
Impact of Aprepitant/5HT-3 Antagonist Therapy on the Patient Quality of Life as Measured by the Number of Patients Using Anti Nausea Drugs
Time frame: Week 1
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Antiemetic, Chemotherapy, and Radiation Therapy) | Impact of Aprepitant/5HT-3 Antagonist Therapy on the Patient Quality of Life as Measured by the Number of Patients Using Anti Nausea Drugs | 6 participants |