Aprepitant in Preventing Nausea and Vomiting in Patients Undergoing Chemotherapy and Radiation Therapy for Pancreatic Cancer

A Feasibility Study to Discern the Tolerability of 5-FU/Gemcitabine Based Chemotherapy Concurrent With Upper Abdominal Radiation and the Utility of Aprepitant/5HT-3 Antagonist (EMEND) for the Prevention of ChemoRadiation-Induced Nausea and Vomiting (CRINV)

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

Study Overview

• Status: Completed
• Conditions: Nausea; Vomiting; Stage III Pancreatic Cancer; Stage IV Pancreatic Cancer; Extrahepatic Bile Duct Cancer; Stage II Pancreatic Cancer
• Intervention / Treatment: Drug: fluorouracil; Other: questionnaire administration; Procedure: quality-of-life assessment; Drug: gemcitabine hydrochloride; Drug: capecitabine; Drug: aprepitant; Procedure: radiation therapy; Procedure: nausea and vomiting therapy; Procedure: management of therapy complications

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.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: 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.

Drug: fluorouracil; Given IV; Other Names: 5-FU; 5-fluorouracil; 5-Fluracil; Other: questionnaire administration; Ancillary studies; Procedure: quality-of-life assessment; Ancillary studies; Other Names: quality of life assessment; Drug: gemcitabine hydrochloride; Given IV; Other Names: Gemzar; gemcitabine; dFdC; difluorodeoxycytidine hydrochloride; Drug: capecitabine; Given PO; Other Names: Xeloda; CAPE; Ro 09-1978/000; Drug: aprepitant; Given PO; Other Names: Emend; L-754030; MK-0869; ONO-7436; Procedure: radiation therapy; Undergo radiation therapy; Other Names: irradiation; radiotherapy; therapy, radiation; Procedure: nausea and vomiting therapy; Receive aprepitant; Other Names: antiemetic support; management of nausea and vomiting; nausea and vomiting management; therapy, nausea and vomiting; vomiting and nausea management; Procedure: management of therapy complications; Receive aprepitant; Other Names: complications of therapy, management of

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Over 10 weeks

Secondary Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Collaborators: National Cancer Institute (NCI); Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start: August 1, 2006
• Primary Completion (ACTUAL): December 1, 2009
• Study Completion (ACTUAL): August 1, 2012

Study Registration Dates

• First Submitted: February 14, 2012
• First Submitted That Met QC Criteria: February 16, 2012
• First Posted (ESTIMATE): February 17, 2012

Study Record Updates

• Last Update Posted (ACTUAL): August 15, 2018
• Last Update Submitted That Met QC Criteria: July 16, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Signs and Symptoms, Digestive; Digestive System Neoplasms; Endocrine Gland Neoplasms; Biliary Tract Diseases; Pancreatic Diseases; Bile Duct Diseases; Biliary Tract Neoplasms; Nausea; Vomiting; Pancreatic Neoplasms; Cholangiocarcinoma; Bile Duct Neoplasms; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gastrointestinal Agents; Neurokinin-1 Receptor Antagonists; Gemcitabine; Fluorouracil; Capecitabine; Aprepitant; Antiemetics
• Other Study ID Numbers: IRB00000209; NCI-2009-01258 (REGISTRY: CTRP (Clinical Trial Reporting Program)); CCCWFU 02205 (OTHER: Wake Forest University Health Sciences)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No