Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Phase II Study of Ibrutinib in Advanced Carcinoid and Pancreatic Neuroendocrine Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02575300
Recruitment Status : Active, not recruiting
First Posted : October 14, 2015
Results First Posted : October 2, 2019
Last Update Posted : October 2, 2019
Sponsor:
Collaborator:
Pharmacyclics LLC.
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Carcinoid Tumors
Pancreatic NET
Intervention Drug: Ibrutinib
Enrollment 20
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Ibrutinib Therapy
Hide Arm/Group Description

Ibrutinib Initial Dose 560 mg by mouth (PO) every day (QD)

Ibrutinib: Ibrutinib will be administered orally once daily and each cycle will be defined as 4 weeks duration. Study treatment should begin within 14 days following enrollment into the study and continue until disease progression, unacceptable toxicity, or withdrawal of consent.

Period Title: Overall Study
Started 20
Completed 20
Not Completed 0
Arm/Group Title Ibrutinib Therapy
Hide Arm/Group Description

Ibrutinib Initial Dose 560 mg by mouth (PO) every day (QD)

Ibrutinib: Ibrutinib will be administered orally once daily and each cycle will be defined as 4 weeks duration. Study treatment should begin within 14 days following enrollment into the study and continue until disease progression, unacceptable toxicity, or withdrawal of consent.

Overall Number of Baseline Participants 20
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants
<=18 years
0
   0.0%
Between 18 and 65 years
9
  45.0%
>=65 years
11
  55.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants
Female
9
  45.0%
Male
11
  55.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants
Hispanic or Latino
2
  10.0%
Not Hispanic or Latino
18
  90.0%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 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
1
   5.0%
White
18
  90.0%
More than one race
0
   0.0%
Unknown or Not Reported
1
   5.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 20 participants
20
1.Primary Outcome
Title Overall Radiographic Response Rate (ORR)
Hide Description

Response rate as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. For this study, measurable disease is defined as the presence of at least one measurable lesion.

Measurable lesions must be accurately measured in at least one dimension (longest diameter in the plane of measurement is to be recorded) with a minimum size of: 10 mm by CT scan (CT scan slice thickness no greater than 5 mm (when CT scans have slice thickness >5 mm, the minimum size should be twice the slice thickness); 10 mm caliper measurement by clinical exam (lesions which cannot be accurately measured with calipers should be recorded as non-measurable); 20 mm by chest X-ray.

Complete Response (CR): complete disappearance of all target lesions, confirmed by repeat assessments at no less than 4 weeks after the criteria for response are first met. Partial Response (PR): at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum longest diameter.

Time Frame Up to 18 months
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study drug.
Arm/Group Title Ibrutinib Therapy
Hide Arm/Group Description:

Ibrutinib Initial Dose 560 mg by mouth (PO) every day (QD)

Ibrutinib: Ibrutinib will be administered orally once daily and each cycle will be defined as 4 weeks duration. Study treatment should begin within 14 days following enrollment into the study and continue until disease progression, unacceptable toxicity, or withdrawal of consent.

Overall Number of Participants Analyzed 20
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
2.Secondary Outcome
Title Progression Free Survival (PFS)
Hide Description Progression free survival at one year. PFS, determined as the time from administration of the initial dose of ibrutinib until objective tumor progression using RECIST, or death. Progressive Disease (PD): at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this may include the baseline sum). The sum must also demonstrate an absolute increase of at least 5 mm.
Time Frame 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ibrutinib Therapy
Hide Arm/Group Description:

Ibrutinib Initial Dose 560 mg by mouth (PO) every day (QD)

Ibrutinib: Ibrutinib will be administered orally once daily and each cycle will be defined as 4 weeks duration. Study treatment should begin within 14 days following enrollment into the study and continue until disease progression, unacceptable toxicity, or withdrawal of consent.

Overall Number of Participants Analyzed 20
Median (95% Confidence Interval)
Unit of Measure: months
3.0
(2.8 to 5.8)
3.Secondary Outcome
Title Overall Survival (OS)
Hide Description Overall Survival determined from the time of drug administration to death from any cause.
Time Frame Up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ibrutinib Therapy
Hide Arm/Group Description:

Ibrutinib Initial Dose 560 mg by mouth (PO) every day (QD)

Ibrutinib: Ibrutinib will be administered orally once daily and each cycle will be defined as 4 weeks duration. Study treatment should begin within 14 days following enrollment into the study and continue until disease progression, unacceptable toxicity, or withdrawal of consent.

Overall Number of Participants Analyzed 20
Median (95% Confidence Interval)
Unit of Measure: months
24.1 [1] 
(16.5 to NA)
[1]
The high end of the range was not reached at time of analysis.
4.Secondary Outcome
Title Occurrence of Possibly Related Adverse Events (AEs)
Time Frame Up to 18 months
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study drug and had at least one adverse event that was possibly probably or definitely related to study treatment.
Arm/Group Title Ibrutinib Therapy
Hide Arm/Group Description:

Ibrutinib Initial Dose 560 mg by mouth (PO) every day (QD)

Ibrutinib: Ibrutinib will be administered orally once daily and each cycle will be defined as 4 weeks duration. Study treatment should begin within 14 days following enrollment into the study and continue until disease progression, unacceptable toxicity, or withdrawal of consent.

Overall Number of Participants Analyzed 20
Measure Type: Count of Participants
Unit of Measure: Participants
19
  95.0%
5.Secondary Outcome
Title Duration of Response
Hide Description Duration of response, defined as time from first observation of an objective response which is subsequently confirmed, to first disease progression or death due to any cause.
Time Frame Up to 18 months
Hide Outcome Measure Data
Hide Analysis Population Description
No participants experienced objective response
Arm/Group Title Ibrutinib Therapy
Hide Arm/Group Description:

Ibrutinib Initial Dose 560 mg by mouth (PO) every day (QD)

Ibrutinib: Ibrutinib will be administered orally once daily and each cycle will be defined as 4 weeks duration. Study treatment should begin within 14 days following enrollment into the study and continue until disease progression, unacceptable toxicity, or withdrawal of consent.

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame 3 years, 5 months
Adverse Event Reporting Description SAEs are reported that occurred after first dose of study drug through 30 days after discontinuation of study drug.
 
Arm/Group Title Ibrutinib Therapy
Hide Arm/Group Description

Ibrutinib Initial Dose 560 mg by mouth (PO) every day (QD)

Ibrutinib: Ibrutinib will be administered orally once daily and each cycle will be defined as 4 weeks duration. Study treatment should begin within 14 days following enrollment into the study and continue until disease progression, unacceptable toxicity, or withdrawal of consent.

All-Cause Mortality
Ibrutinib Therapy
Affected / at Risk (%)
Total   9/20 (45.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Ibrutinib Therapy
Affected / at Risk (%) # Events
Total   2/20 (10.00%)    
Gastrointestinal disorders   
Abdominal Pain * 1  1/20 (5.00%)  1
Small Intestinal Obstruction * 1  1/20 (5.00%)  1
Musculoskeletal and connective tissue disorders   
Back Pain * 1  1/20 (5.00%)  1
Generalized Muscle Weakness * 1  1/20 (5.00%)  1
1
Term from vocabulary, CTCAE (4.0)
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Ibrutinib Therapy
Affected / at Risk (%) # Events
Total   20/20 (100.00%)    
Blood and lymphatic system disorders   
Anemia * 1  1/20 (5.00%)  5
Cardiac disorders   
Palpitations * 1  1/20 (5.00%)  1
Sinus tachycardia * 1  1/20 (5.00%)  1
Eye disorders   
Cataracts * 1  1/20 (5.00%)  1
Gastrointestinal disorders   
Abdominal pain * 1  8/20 (40.00%)  17
Bloating * 1  2/20 (10.00%)  3
Constipation * 1  3/20 (15.00%)  3
Diarrhea * 1  11/20 (55.00%)  28
Dyspepsia * 1  3/20 (15.00%)  7
Dysphagia * 1  1/20 (5.00%)  1
Flatulence * 1  6/20 (30.00%)  9
Gastrointestinal disorders, other * 1 [1]  1/20 (5.00%)  1
Hemorrhoidal hemorrhage * 1  1/20 (5.00%)  1
Gastrointestinal Disorders, other * 1 [2]  1/20 (5.00%)  1
Mucositis oral * 1  1/20 (5.00%)  1
Nausea * 1  10/20 (50.00%)  26
Oral pain * 1  1/20 (5.00%)  1
Small intestinal obstruction * 1  1/20 (5.00%)  1
Stomach Pain * 1  1/20 (5.00%)  2
Vomiting * 1  4/20 (20.00%)  13
General disorders   
Chills * 1  1/20 (5.00%)  1
Edema limbs * 1  1/20 (5.00%)  1
Fatigue * 1  11/20 (55.00%)  17
Flu like symptoms * 1  2/20 (10.00%)  3
Irritability * 1  2/20 (10.00%)  2
Neck edema * 1  1/20 (5.00%)  1
Pain * 1  2/20 (10.00%)  2
General disorders and administration site conditions - Other * 1 [3]  1/20 (5.00%)  1
General disorders and administration site conditions - Other * 1 [4]  1/20 (5.00%)  1
General disorders and administration site conditions - Other * 1 [5]  1/20 (5.00%)  1
Immune system disorders   
Anaphylaxis * 1  1/20 (5.00%)  2
Infections and infestations   
Lung infection * 1  1/20 (5.00%)  1
Sinusitis * 1  1/20 (5.00%)  1
Upper respiratory infection * 1  3/20 (15.00%)  5
Urinary tract infection * 1  1/20 (5.00%)  2
Injury, poisoning and procedural complications   
Bruising * 1  1/20 (5.00%)  2
Injury, poisoning and procedural complications - Other * 1 [6]  1/20 (5.00%)  1
Investigations   
Alanine aminotransferase increased * 1  3/20 (15.00%)  9
Aspartate aminotransferase increased * 1  2/20 (10.00%)  4
Creatinine increased * 1  1/20 (5.00%)  1
Lymphocyte count decreased * 1  2/20 (10.00%)  2
Platelet count decreased * 1  1/20 (5.00%)  1
Weight loss * 1  2/20 (10.00%)  2
Metabolism and nutrition disorders   
Anorexia * 1  3/20 (15.00%)  3
Hypercalcemia * 1  1/20 (5.00%)  2
Hyperglycemia * 1  2/20 (10.00%)  2
Hypoalbuminemia * 1  1/20 (5.00%)  1
Hypoglycemia * 1  1/20 (5.00%)  1
Hypokalemia * 1  3/20 (15.00%)  3
Hyponatremia * 1  1/20 (5.00%)  1
Metabolism and nutrition disorders - Other * 1 [7]  1/20 (5.00%)  1
Musculoskeletal and connective tissue disorders   
Arthralgia * 1  7/20 (35.00%)  12
Arthritis * 1  1/20 (5.00%)  2
Back Pain * 1  4/20 (20.00%)  11
Flank pain * 1  1/20 (5.00%)  1
Generalized muscle weakness * 1  1/20 (5.00%)  1
Myalgia * 1  3/20 (15.00%)  3
Neck pain * 1  1/20 (5.00%)  1
Pain in extremity * 1  1/20 (5.00%)  1
Musculoskeletal and connective tissue disorder - Other * 1 [8]  2/20 (10.00%)  5
Musculoskeletal and connective tissue disorder - other * 1 [9]  1/20 (5.00%)  1
Musculoskeletal and connective tissue disorder - Other * 1 [10]  1/20 (5.00%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Neoplasms benign, malignant and unspecified - Other * 1 [11]  1/20 (5.00%)  1
Nervous system disorders   
Dizziness * 1  5/20 (25.00%)  8
Dysphasia * 1  1/20 (5.00%)  1
Headache * 1  5/20 (25.00%)  5
Memory impairment * 1  1/20 (5.00%)  1
Parasethesia * 1  1/20 (5.00%)  1
Peripheral motor neuropathy * 1  1/20 (5.00%)  2
Syncope * 1  1/20 (5.00%)  1
Psychiatric disorders   
Agitation * 1  1/20 (5.00%)  1
Anxiety * 1  1/20 (5.00%)  1
Depression * 1  2/20 (10.00%)  2
Insomnia * 1  1/20 (5.00%)  1
Renal and urinary disorders   
Hematuria * 1  1/20 (5.00%)  1
Urinary frequency * 1  2/20 (10.00%)  2
Urinary tract pain * 1  1/20 (5.00%)  1
Respiratory, thoracic and mediastinal disorders   
Cough * 1  2/20 (10.00%)  3
Dyspnea * 1  3/20 (15.00%)  3
Epistaxis * 1  1/20 (5.00%)  1
Hoarseness * 1  1/20 (5.00%)  2
Respiratory, thoracic and mediastinal disorders-other * 1  2/20 (10.00%)  5
Sore throat * 1  1/20 (5.00%)  1
Skin and subcutaneous tissue disorders   
Dry skin * 1  1/20 (5.00%)  1
Rash maculo-papular * 1  5/20 (25.00%)  5
Skin and subcutaneous tissue disorders - Other * 1 [12]  1/20 (5.00%)  1
Skin and subcutaneous tissue disorders - Other * 1 [13]  1/20 (5.00%)  1
Skin and Subcutaneous tissue disorders -Other * 1 [14]  1/20 (5.00%)  1
Skin and Subcutaneous tissue disorders - Other * 1 [15]  1/20 (5.00%)  1
Vascular disorders   
Flushing * 1  3/20 (15.00%)  4
Hot flashes * 1  1/20 (5.00%)  2
Hypertension * 1  4/20 (20.00%)  8
Hypotension * 1  1/20 (5.00%)  1
1
Term from vocabulary, CTCAE (4.0)
*
Indicates events were collected by non-systematic assessment
[1]
Upset stomach
[2]
Malabsorption
[3]
Night sweats
[4]
Sweats (per diary)
[5]
Flu like symptoms
[6]
Right ankle sprain
[7]
Diabetes
[8]
Hip pain
[9]
Left hip pain
[10]
Leg muscle cramps
[11]
Basal cell carcinoma
[12]
Brittle nails
[13]
Non-puritic rash
[14]
Hair breakage
[15]
Right forearm skin lesion
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Jonathan Strosberg, MD
Organization: H. Lee Moffitt Cancer and Research Center
Phone: 813-745-7257
EMail: Jonathan.Strosberg@moffitt.org
Layout table for additonal information
Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT02575300     History of Changes
Other Study ID Numbers: MCC-18141
First Submitted: October 12, 2015
First Posted: October 14, 2015
Results First Submitted: August 16, 2019
Results First Posted: October 2, 2019
Last Update Posted: October 2, 2019