Safety and Efficacy of Avelumab in Small Intestinal Adenocarcinoma

• ClinicalTrials.gov Identifier: NCT03000179
• Recruitment Status: Terminated
• First Posted: December 21, 2016
• Results First Posted: April 14, 2022
• Last Update Posted: April 14, 2022
• Sponsor: Vanderbilt-Ingram Cancer Center
• Collaborators: National Cancer Institute (NCI); EMD Serono
• Information provided by (Responsible Party): Dana Cardin, MD, Vanderbilt-Ingram Cancer Center

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Adenocarcinoma
• Intervention: Drug: Avelumab
• Enrollment: 8

Participant Flow

Recruitment Details	Participants were enrolled onto this study at Vanderbilt University Medical Center in Nashville, TN from March 2017 to August 2019. The study closed early due to low accrual.
Pre-assignment Details

Arm/Group Title	Avelumab Monotherapy
Arm/Group Description	Participants receive avelumab by IV infusion following pretreatment with H1 blockers and acetaminophen once every 2 weeks. Avelumab: Avelumab through a vein once every 2 weeks
Period Title: Overall Study
Started	8
Completed	6
Not Completed	2
Reason Not Completed
Lost to Follow-up	2

Baseline Characteristics

Arm/Group Title		Avelumab Monotherapy
Arm/Group Description		Participants receive avelumab by IV infusion following pretreatment with H1 blockers and acetaminophen once every 2 weeks. Avelumab: Avelumab through a vein once every 2 weeks
Overall Number of Baseline Participants		8
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	8 participants
	<=18 years	0 0.0%
	Between 18 and 65 years	3 37.5%
	>=65 years	5 62.5%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	8 participants
	Female	1 12.5%
	Male	7 87.5%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	8 participants
	Hispanic or Latino	0 0.0%
	Not Hispanic or Latino	7 87.5%
	Unknown or Not Reported	1 12.5%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	8 participants
	American Indian or Alaska Native	0 0.0%
	Asian	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	0 0.0%
	White	8 100.0%
	More than one race	0 0.0%
	Unknown or Not Reported	0 0.0%
Region of Enrollment; Measure Type: Count of Participants; Unit of measure: Participants
United States	Number Analyzed	8 participants
		8 100.0%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate as Measured Using RECIST 1.1
Description	Response rate is the proportion of patients with overall complete (CR) or partial response(PR) among patients with valuable response outcome. Overall response will consider both target and non-target lesions, as well as new lesions. Target lesions by CT/MRI: CR: Disappearance of all target lesions. PR: >= 30% decrease in the sum of diameters of target lesions. Progressive Disease (PD): >= 20% increase in the sum of diameters of target lesions, In addition, the sum must also demonstrate an absolute increase of at least 5 mm or appearance of new lesions. Non-target lesions: CR: Disappearance of all target lesions. Non-CR/Non-PD: Persistence of one or more non-target lesion(s) and/or maintenance of applicable tumor marker level above the normal limits. PD: progression of existing non-target lesions.
Time Frame	Measured every 8 weeks through study completion, an average of 1 year

Outcome Measure Data

Analysis Population Description

Patients with advanced small intestinal adenocarcinoma or ampullary tumors, efficacy-evaluable.

Arm/Group Title	Avelumab Monotherapy
Arm/Group Description:	Participants receive avelumab by IV infusion following pretreatment with H1 blockers and acetaminophen once every 2 weeks. Avelumab: Avelumab through a vein once every 2 weeks
Overall Number of Participants Analyzed	7
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: proportion of participants
	0.29; (0.08 to 0.64)

2. Primary Outcome

Title	Number of Patients With Each Worst-Grade Toxicity
Description	To describe the safety profile of avelumab monotherapy in patients with advanced or metastatic small intestinal adenocarcinoma
Time Frame	On-study date to 30 days following final dose of study drug, or until the event is resolved, stabilized, or determined to be irreversible by the participating investigator if beyond 30 days.

Outcome Measure Data

Analysis Population Description

all participants

Arm/Group Title	Avelumab Monotherapy
Arm/Group Description:	Participants receive avelumab by IV infusion following pretreatment with H1 blockers and acetaminophen once every 2 weeks. Avelumab: Avelumab through a vein once every 2 weeks
Overall Number of Participants Analyzed	8
Measure Type: Count of Participants; Unit of Measure: Participants
Anemia, Grade 1	2 25.0%
Fatigue, Grade2	1 12.5%
Infusion related reaction. Grade2	2 25.0%
Alanine aminotransferase increased, Grade 1	1 12.5%
Alkaline phosphatase increased, Grade 1	1 12.5%
Anorexia, Grade 2	1 12.5%
Blood bilirubin increased, Grade1	1 12.5%
Diarrhea, Grade 1	1 12.5%
Diabetic ketoacidosis, Grade 4	1 12.5%
Back pain, Grade 1	1 12.5%
Diverticulitis per upper GI series, Grade 2	1 12.5%
Hypokalemia, Grade 3	1 12.5%
Hyponatremia, Grade 3	1 12.5%
Nausea, Grade 2	1 12.5%
Rash maculo-papular, Grade 1	1 12.5%
Urticaria, Grade 1	1 12.5%

3. Secondary Outcome

Title	Overall Survival
Description	On study date until death from any cause
Time Frame	Every 3 months after completing treatment up to 5 years

Outcome Measure Data

Analysis Population Description

all participants

Arm/Group Title	Avelumab Monotherapy
Arm/Group Description:	Participants receive avelumab by IV infusion following pretreatment with H1 blockers and acetaminophen once every 2 weeks. Avelumab: Avelumab through a vein once every 2 weeks
Overall Number of Participants Analyzed	8
Median (95% Confidence Interval); Unit of Measure: months
	6.4 [1]; (3.8 to NA)

[1]

Insufficient number of patients with the death event

4. Secondary Outcome

Title	Progression Free Survival
Description	On-study date until disease progression or death. Progression is >= 20% increase in the sum of diameters of target lesions or non-target lesions, or appearance of new lesions.
Time Frame	On-study date to lesser of date of progression or date of death from any cause measured up to 3 years after treatment

Outcome Measure Data

Analysis Population Description

all participants

Arm/Group Title	Avelumab Monotherapy
Arm/Group Description:	Participants receive avelumab by IV infusion following pretreatment with H1 blockers and acetaminophen once every 2 weeks. Avelumab: Avelumab through a vein once every 2 weeks
Overall Number of Participants Analyzed	8
Median (95% Confidence Interval); Unit of Measure: months
	3.4 [1]; (3.0 to NA)

[1]

Insufficient number of patients with progression.

5. Secondary Outcome

Title	Duration of Response
Description	Time from tumor response date to disease progression or death for any reason.
Time Frame	Date of first partial or complete response as defined by RECIST 1.1 criteria to date of recurrence or disease progression up to 3 years

Outcome Measure Data

Analysis Population Description

Patients who had partial response.

Arm/Group Title	Avelumab Monotherapy
Arm/Group Description:	Participants receive avelumab by IV infusion following pretreatment with H1 blockers and acetaminophen once every 2 weeks. Avelumab: Avelumab through a vein once every 2 weeks
Overall Number of Participants Analyzed	2
Median (Full Range); Unit of Measure: months
	10.9; (3.0 to 18.8)

Adverse Events

Time Frame	From study entry to up to 28 days from the last dose of avelumab up to approximately 1 year.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Avelumab Monotherapy
Arm/Group Description	Participants receive avelumab by IV infusion following pretreatment with H1 blockers and acetaminophen once every 2 weeks. Avelumab: Avelumab through a vein once every 2 weeks
All-Cause Mortality
	Avelumab Monotherapy
	Affected / at Risk (%)
Total	6/8 (75.00%)
Serious Adverse Events
	Avelumab Monotherapy
	Affected / at Risk (%)	# Events
Total	7/8 (87.50%)
Blood and lymphatic system disorders
Anemia † 1	1/8 (12.50%)	1
Endocrine disorders
Diabetic Ketoacidos † 1	1/8 (12.50%)	1
Gastrointestinal disorders
Gastroenteritis † 1	1/8 (12.50%)	1
Nausea † 1	1/8 (12.50%)	1
Abdominal pain † 1	1/8 (12.50%)	1
Ascites † 1	1/8 (12.50%)	1
Colonic obstruction † 1	1/8 (12.50%)	1
Infections and infestations
Bacteremia bloodstream infection † 1	1/8 (12.50%)	1
Injury, poisoning and procedural complications
Sepsis † 1	1/8 (12.50%)	1
Metabolism and nutrition disorders
Hyponatremia † 1	1/8 (12.50%)	1
Nervous system disorders
Ataxia † 1	1/8 (12.50%)	1
Vascular disorders
Thromboembolic event † 1	1/8 (12.50%)	1
1 Term from vocabulary, CTCAE (Unspecified); † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Avelumab Monotherapy
	Affected / at Risk (%)	# Events
Total	8/8 (100.00%)
Blood and lymphatic system disorders
Anemia † 1	7/8 (87.50%)	20
Cardiac disorders
Chest pain † 1	1/8 (12.50%)	2
Sinus tachycardia † 1	1/8 (12.50%)	1
Ear and labyrinth disorders
Vertigo † 1	1/8 (12.50%)	1
Endocrine disorders
Adrenal insufficiency † 1	1/8 (12.50%)	1
Eye disorders
Blurred vision † 1	1/8 (12.50%)	1
Gastrointestinal disorders
Abdominal pain † 1	5/8 (62.50%)	7
Nausea † 1	5/8 (62.50%)	7
Vomiting † 1	4/8 (50.00%)	6
Constipation † 1	2/8 (25.00%)	2
Diarrhea † 1	2/8 (25.00%)	3
Abdominal distension † 1	1/8 (12.50%)	1
Dyspepsia † 1	1/8 (12.50%)	1
Dysphagia † 1	1/8 (12.50%)	1
Flatulence † 1	1/8 (12.50%)	1
Gastrointestinal fistula † 1	1/8 (12.50%)	1
Small intestinal mucositis † 1	1/8 (12.50%)	1
General disorders
Fatigue † 1	4/8 (50.00%)	5
Fever † 1	2/8 (25.00%)	4
Chills † 1	1/8 (12.50%)	1
Limb edema † 1	1/8 (12.50%)	1
Facial pain † 1	1/8 (12.50%)	1
Gait disturbance † 1	1/8 (12.50%)	1
Infusion related reaction † 1	1/8 (12.50%)	1
Infections and infestations
Mucosal infection † 1	2/8 (25.00%)	2
Lung infection † 1	1/8 (12.50%)	1
Small intestine infection † 1	1/8 (12.50%)	1
Upper respiratory infection † 1	1/8 (12.50%)	1
Injury, poisoning and procedural complications
Fall † 1	2/8 (25.00%)	2
Investigations
Lymphocyte count decreased † 1	4/8 (50.00%)	8
Alkaline phosphatase increased † 1	3/8 (37.50%)	8
Weight loss † 1	3/8 (37.50%)	5
Activated partial thromboplastin time prolonged † 1	2/8 (25.00%)	3
Alanine aminotransferase increased † 1	2/8 (25.00%)	2
Blood bilirubin increased † 1	2/8 (25.00%)	2
Aspartate aminotransferase increased † 1	1/8 (12.50%)	2
INR increased † 1	1/8 (12.50%)	1
White blood cell decreased † 1	1/8 (12.50%)	1
Hypocalcemia † 1	2/8 (25.00%)	7
Metabolism and nutrition disorders
Hypoalbuminemia † 1	3/8 (37.50%)	8
Hyponatremia † 1	3/8 (37.50%)	5
Hypercalcemia † 1	2/8 (25.00%)	2
Hypokalemia † 1	2/8 (25.00%)	2
Anorexia † 1	1/8 (12.50%)	2
Dehydration † 1	1/8 (12.50%)	1
Hyperkalemia † 1	1/8 (12.50%)	2
Hyperuricemia † 1	1/8 (12.50%)	1
Hypomagnesemia † 1	1/8 (12.50%)	1
Musculoskeletal and connective tissue disorders
Neck pain † 1	2/8 (25.00%)	4
Back pain † 1	1/8 (12.50%)	2
Generalized muscle weaknes † 1	1/8 (12.50%)	1
Myalgia † 1	1/8 (12.50%)	1
Extremity pain † 1	1/8 (12.50%)	1
Nervous system disorders
Headache † 1	2/8 (25.00%)	3
Syncope † 1	2/8 (25.00%)	2
Dizziness † 1	1/8 (12.50%)	1
memory impairement † 1	1/8 (12.50%)	1
Presyncope † 1	1/8 (12.50%)	1
Thromboembolic event † 1	2/8 (25.00%)	2
Psychiatric disorders
Anxiety † 1	1/8 (12.50%)	1
Confusion † 1	1/8 (12.50%)	1
Depression † 1	1/8 (12.50%)	1
Insomnia † 1	1/8 (12.50%)	2
Psychosis † 1	1/8 (12.50%)	2
Restlessness † 1	1/8 (12.50%)	1
Renal and urinary disorders
Proteinuria † 1	3/8 (37.50%)	3
Hematuria † 1	1/8 (12.50%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea † 1	3/8 (37.50%)	3
Allergic rhinitis † 1	2/8 (25.00%)	2
Couph † 1	1/8 (12.50%)	1
Skin and subcutaneous tissue disorders
Dry skin † 1	1/8 (12.50%)
Photosensitivity † 1	1/8 (12.50%)	1
Pruritus † 1	1/8 (12.50%)	1
Rash maculo-papular † 1	1/8 (12.50%)	1
Urticaria † 1	1/8 (12.50%)	1
Vascular disorders
Hypertension † 1	2/8 (25.00%)	3
Phlebitis † 1	1/8 (12.50%)	1
1 Term from vocabulary, CTCAE (Unspecified); † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

Results Point of Contact

• Name/Title: Teresa Melton
• Organization: Vanderbilt-Ingram Cancer Center
• Phone: 615-936-7423
• EMail: teresa.melton@vumc.org

• Responsible Party: Dana Cardin, MD, Vanderbilt-Ingram Cancer Center
• ClinicalTrials.gov Identifier: NCT03000179
• Other Study ID Numbers: VICC GI 1679
• First Submitted: December 6, 2016
• First Posted: December 21, 2016
• Results First Submitted: February 18, 2022
• Results First Posted: April 14, 2022
• Last Update Posted: April 14, 2022