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

• Sponsor: Wake Forest University Health Sciences (Other)
• Overall Status: Completed
• CT.gov ID: NCT01534637
• Collaborator: National Cancer Institute (NCI) (NIH), Merck Sharp & Dohme LLC (Industry)
• Enrollment: 22
• Location: 1
• Arm: 1
• Duration (Months): 72
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Extrahepatic Bile Duct Cancer; Nausea; Vomiting; Stage II Pancreatic Cancer; Stage III Pancreatic Cancer; Stage IV Pancreatic Cancer	Drug: aprepitant; Drug: gemcitabine hydrochloride; Drug: capecitabine; Drug: fluorouracil; Procedure: radiation therapy; Other: questionnaire administration; Procedure: quality-of-life assessment; Procedure: nausea and vomiting therapy; Procedure: management of therapy complications	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. Discern the gastrointestinal toxicities associated with 5-FU (fluorouracil)/Gemcitabine (gemcitabine hydrochloride) chemotherapy when combined with upper abdominal radiation therapy.

2. 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:

1. 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 Design

• Study Type: Interventional
• Actual Enrollment: 22 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: 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)
• Study Start Date: Aug 1, 2006
• Actual Primary Completion Date: Dec 1, 2009
• Actual Study Completion Date: Aug 1, 2012

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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]

2. 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]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157

Sponsors and Collaborators

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

Investigators

• Principal Investigator: Arthur Blackstock, Wake Forest University Health Sciences

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Wake Forest University Health Sciences
• ClinicalTrials.gov Identifier: NCT01534637
• Other Study ID Numbers: IRB00000209; NCI-2009-01258; CCCWFU 02205; NCT00398164
• First Posted: Feb 17, 2012
• Last Update Posted: Aug 15, 2018
• Last Verified: Jul 1, 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Pancreatic Neoplasms; Bile Duct Neoplasms; Cholangiocarcinoma; Nausea; Vomiting; Gemcitabine; Fluorouracil; Capecitabine; Aprepitant; Antiemetics

Study Results

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.

Arm/Group Title	Treatment (Antiemetic, Chemotherapy, and Radiation Therapy)
Arm/Group Description	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.
Period Title: Overall Study
STARTED	22
COMPLETED	13
NOT COMPLETED	9

Baseline Characteristics

Arm/Group Title	Treatment (Antiemetic, Chemotherapy, and Radiation Therapy)
Arm/Group Description	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.
Overall Participants	20
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	13 65%
>=65 years	7 35%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.4 (11.4)
Sex: Female, Male (Count of Participants)
Female	9 45%
Male	11 55%
Region of Enrollment (participants) [Number]
United States	20 100%

Outcome Measures

1. Primary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Antiemetic, Chemotherapy, and Radiation Therapy)
Arm/Group Description	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.
Measure Participants	20
Number [participants]	3 15%

2. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Antiemetic, Chemotherapy, and Radiation Therapy)
Arm/Group Description	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.
Measure Participants	19
Number [participants]	6 30%

3. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Antiemetic, Chemotherapy, and Radiation Therapy)
Arm/Group Description	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.
Measure Participants	15
Number [participants]	5 25%

Adverse Events

Arm/Group Title	Treatment (Antiemetic, Chemotherapy, and Radiation Therapy)
Arm/Group Description	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.
All Cause Mortality
	Treatment (Antiemetic, Chemotherapy, and Radiation Therapy)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Antiemetic, Chemotherapy, and Radiation Therapy)
	Affected / at Risk (%)	# Events
Total	4/21 (19%)
Blood and lymphatic system disorders
Low Leukocytes (total WBC)	1/21 (4.8%)	1
Neutrophils/granulocytes (ANC/AGC)	1/21 (4.8%)	1
Lymphopenia	2/21 (9.5%)	2
Gastrointestinal disorders
Anorexia	1/21 (4.8%)	1
Nausea	1/21 (4.8%)	1
Vomiting	1/21 (4.8%)	1
Metabolism and nutrition disorders
Sodium, serum-low (hyponatremia)	1/21 (4.8%)	1
Potassium, serum-low (hypokalemia)	2/21 (9.5%)	2
Potassium, serum-high (hyperkalemia)	1/21 (4.8%)	1
Nervous system disorders
Pain: Abdomen	2/21 (9.5%)	2
Vascular disorders
Thrombosis/thrombus/embolism	1/21 (4.8%)	1
Other (Not Including Serious) Adverse Events
	Treatment (Antiemetic, Chemotherapy, and Radiation Therapy)
	Affected / at Risk (%)	# Events
Total	5/21 (23.8%)
Blood and lymphatic system disorders
Leukocytes (total WBC)	4/21 (19%)	4
Platelets	2/21 (9.5%)	2
Hemoglobin	5/21 (23.8%)	5
Nausea	2/21 (9.5%)	2
Neutrophils/granulocytes	4/21 (19%)	4
Gastrointestinal disorders
nausea	2/21 (9.5%)	2
Metabolism and nutrition disorders
Albumin, serum-low	2/21 (9.5%)	2
Dehydration	2/2 (100%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.