Trial Outcomes & Findings for Randomized Phase II Trial of Pre-Operative Gemcitabine and Nab Paclitacel With or With Out Hydroxychloroquine (NCT NCT01978184)
NCT ID: NCT01978184
Last Updated: 2019-03-27
Results Overview
The number of patients who exhibited an Evans grade Histologic response (I, IIA, IIB, or III) to pre-operative gemcitabine / nab-paclitaxel. Histological response validated scoring system by Evans is as follows: Grade I: 1-9% tumor destruction, Grade II: 10 - 90%, Grade III: \>90% tumor destruction (Grade IIA = 10-50% of tumor cells destroyed; Grade IIB = 50-90% of tumor cells destroyed), Grade IV: Absence of viable tumor cells.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
104 participants
Primary outcome timeframe
Up to 4 years
Results posted on
2019-03-27
Participant Flow
Participant milestones
| Measure |
Gemcitabine + Abraxane
Gemcitabine and Abraxane administered as an intravenous infusion on Study Days 3, 10, 17, 31, 38, and 45. Day 3 dosing: 1 hour infusion - 1000 mg/m\^2 of gemcitabine followed by a 125 mg/m\^2 of abraxane. Prior to each gemcitabine infusion, subjects were pre-medicated with an FDA-approved anti-emetic (anti-nausea medication) in an effort to prevent nausea, at the discretion of the study physician.
|
Gemcitabine + Abraxane and Hydroxychloroquine
Gemcitabine and Abraxane administered as an intravenous infusion on Study Days 3, 10, 17, 31, 38, and 45. Day 3 dosing: 1 hour infusion - 1000 mg/m\^2 of gemcitabine followed by a 125 mg/m\^2 of abraxane. Prior to each gemcitabine infusion, subjects were pre-medicated with an FDA-approved anti-emetic (anti-nausea medication) in an effort to prevent nausea, at the discretion of the study physician.
Hydroxychloroquine oral capsules taken once or twice a daily at a dose of 1200mg. The first dose of hydroxychloroquine taken on Day 1 (48 hours before the first infusion of gemcitabine/abraxane), and continued daily until one day before surgery.
|
|---|---|---|
|
Overall Study
STARTED
|
43
|
61
|
|
Overall Study
COMPLETED
|
30
|
41
|
|
Overall Study
NOT COMPLETED
|
13
|
20
|
Reasons for withdrawal
| Measure |
Gemcitabine + Abraxane
Gemcitabine and Abraxane administered as an intravenous infusion on Study Days 3, 10, 17, 31, 38, and 45. Day 3 dosing: 1 hour infusion - 1000 mg/m\^2 of gemcitabine followed by a 125 mg/m\^2 of abraxane. Prior to each gemcitabine infusion, subjects were pre-medicated with an FDA-approved anti-emetic (anti-nausea medication) in an effort to prevent nausea, at the discretion of the study physician.
|
Gemcitabine + Abraxane and Hydroxychloroquine
Gemcitabine and Abraxane administered as an intravenous infusion on Study Days 3, 10, 17, 31, 38, and 45. Day 3 dosing: 1 hour infusion - 1000 mg/m\^2 of gemcitabine followed by a 125 mg/m\^2 of abraxane. Prior to each gemcitabine infusion, subjects were pre-medicated with an FDA-approved anti-emetic (anti-nausea medication) in an effort to prevent nausea, at the discretion of the study physician.
Hydroxychloroquine oral capsules taken once or twice a daily at a dose of 1200mg. The first dose of hydroxychloroquine taken on Day 1 (48 hours before the first infusion of gemcitabine/abraxane), and continued daily until one day before surgery.
|
|---|---|---|
|
Overall Study
Progressive disease
|
5
|
5
|
|
Overall Study
Other than PDA
|
2
|
2
|
|
Overall Study
Physician Decision
|
0
|
3
|
|
Overall Study
Noncompliance
|
1
|
2
|
|
Overall Study
Death
|
1
|
0
|
|
Overall Study
Withdrew- toxicities or physical decline
|
4
|
8
|
Baseline Characteristics
Randomized Phase II Trial of Pre-Operative Gemcitabine and Nab Paclitacel With or With Out Hydroxychloroquine
Baseline characteristics by cohort
| Measure |
Gemcitabine + Abraxane
n=30 Participants
Gemcitabine and Abraxane administered as an intravenous infusion on Study Days 3, 10, 17, 31, 38, and 45. Day 3 dosing: 1 hour infusion - 1000 mg/m\^2 of gemcitabine followed by a 125 mg/m\^2 of abraxane. Prior to each gemcitabine infusion, subjects were pre-medicated with an FDA-approved anti-emetic (anti-nausea medication) in an effort to prevent nausea, at the discretion of the study physician.
|
Gemcitabine + Abraxane and Hydroxychloroquine
n=41 Participants
Gemcitabine and Abraxane administered as an intravenous infusion on Study Days 3, 10, 17, 31, 38, and 45. Day 3 dosing: 1 hour infusion - 1000 mg/m\^2 of gemcitabine followed by a 125 mg/m\^2 of abraxane. Prior to each gemcitabine infusion, subjects were pre-medicated with an FDA-approved anti-emetic (anti-nausea medication) in an effort to prevent nausea, at the discretion of the study physician.
Hydroxychloroquine oral capsules taken once or twice a daily at a dose of 1200mg. The first dose of hydroxychloroquine taken on Day 1 (48 hours before the first infusion of gemcitabine/abraxane), and continued daily until one day before surgery.
|
Total
n=71 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
63.6 years
STANDARD_DEVIATION 11.8 • n=5 Participants
|
66.1 years
STANDARD_DEVIATION 8.4 • n=7 Participants
|
65 years
STANDARD_DEVIATION 10 • n=5 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
31 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
40 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
30 Participants
n=5 Participants
|
40 Participants
n=7 Participants
|
70 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
28 Participants
n=5 Participants
|
38 Participants
n=7 Participants
|
66 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 4 yearsPopulation: Patients who went to surgery and were evaluable for Evans Grade Histopathologic Response.
The number of patients who exhibited an Evans grade Histologic response (I, IIA, IIB, or III) to pre-operative gemcitabine / nab-paclitaxel. Histological response validated scoring system by Evans is as follows: Grade I: 1-9% tumor destruction, Grade II: 10 - 90%, Grade III: \>90% tumor destruction (Grade IIA = 10-50% of tumor cells destroyed; Grade IIB = 50-90% of tumor cells destroyed), Grade IV: Absence of viable tumor cells.
Outcome measures
| Measure |
Gemcitabine + Abraxane
n=30 Participants
Gemcitabine and Abraxane administered as an intravenous infusion on Study Days 3, 10, 17, 31, 38, and 45. Day 3 dosing: 1 hour infusion - 1000 mg/m\^2 of gemcitabine followed by a 125 mg/m\^2 of abraxane. Prior to each gemcitabine infusion, subjects were pre-medicated with an FDA-approved anti-emetic (anti-nausea medication) in an effort to prevent nausea, at the discretion of the study physician.
|
Gemcitabine + Abraxane and Hydroxychloroquine
n=41 Participants
Gemcitabine and Abraxane administered as an intravenous infusion on Study Days 3, 10, 17, 31, 38, and 45. Day 3 dosing: 1 hour infusion - 1000 mg/m\^2 of gemcitabine followed by a 125 mg/m\^2 of abraxane. Prior to each gemcitabine infusion, subjects were pre-medicated with an FDA-approved anti-emetic (anti-nausea medication) in an effort to prevent nausea, at the discretion of the study physician.
Hydroxychloroquine oral capsules taken once or twice a daily at a dose of 1200mg. The first dose of hydroxychloroquine taken on Day 1 (48 hours before the first infusion of gemcitabine/abraxane), and continued daily until one day before surgery.
|
|---|---|---|
|
Evans Grade Histopathologic Response
Evans grade - I
|
10 number of participants
|
7 number of participants
|
|
Evans Grade Histopathologic Response
Evans grade - IIA
|
17 number of participants
|
12 number of participants
|
|
Evans Grade Histopathologic Response
Evans grade - IIB
|
3 number of participants
|
13 number of participants
|
|
Evans Grade Histopathologic Response
Evans grade - III
|
0 number of participants
|
9 number of participants
|
PRIMARY outcome
Timeframe: Baseline - At the time of diagnosis, prior to treatmentPopulation: Patients who went to surgery and were evaluable for Evans Grade Histopathologic Response.
The mean age of patients at the time of diagnosis of disease (as a variable in the proportional odds logistic regression, secondary analysis of Evans Grade).
Outcome measures
| Measure |
Gemcitabine + Abraxane
n=30 Participants
Gemcitabine and Abraxane administered as an intravenous infusion on Study Days 3, 10, 17, 31, 38, and 45. Day 3 dosing: 1 hour infusion - 1000 mg/m\^2 of gemcitabine followed by a 125 mg/m\^2 of abraxane. Prior to each gemcitabine infusion, subjects were pre-medicated with an FDA-approved anti-emetic (anti-nausea medication) in an effort to prevent nausea, at the discretion of the study physician.
|
Gemcitabine + Abraxane and Hydroxychloroquine
n=41 Participants
Gemcitabine and Abraxane administered as an intravenous infusion on Study Days 3, 10, 17, 31, 38, and 45. Day 3 dosing: 1 hour infusion - 1000 mg/m\^2 of gemcitabine followed by a 125 mg/m\^2 of abraxane. Prior to each gemcitabine infusion, subjects were pre-medicated with an FDA-approved anti-emetic (anti-nausea medication) in an effort to prevent nausea, at the discretion of the study physician.
Hydroxychloroquine oral capsules taken once or twice a daily at a dose of 1200mg. The first dose of hydroxychloroquine taken on Day 1 (48 hours before the first infusion of gemcitabine/abraxane), and continued daily until one day before surgery.
|
|---|---|---|
|
Age at Diagnosis
|
63.6 years
Standard Deviation 11.8
|
66.1 years
Standard Deviation 8.4
|
PRIMARY outcome
Timeframe: Baseline - At the time of diagnosis, prior to treatmentPopulation: Patients who went to surgery and were evaluable for Evans Grade Histopathologic Response.
Tumor size as measured via computerized tomography (CT) scan (as a variable in the proportional odds logistic regression, secondary analysis of Evans Grade).
Outcome measures
| Measure |
Gemcitabine + Abraxane
n=29 Participants
Gemcitabine and Abraxane administered as an intravenous infusion on Study Days 3, 10, 17, 31, 38, and 45. Day 3 dosing: 1 hour infusion - 1000 mg/m\^2 of gemcitabine followed by a 125 mg/m\^2 of abraxane. Prior to each gemcitabine infusion, subjects were pre-medicated with an FDA-approved anti-emetic (anti-nausea medication) in an effort to prevent nausea, at the discretion of the study physician.
|
Gemcitabine + Abraxane and Hydroxychloroquine
n=41 Participants
Gemcitabine and Abraxane administered as an intravenous infusion on Study Days 3, 10, 17, 31, 38, and 45. Day 3 dosing: 1 hour infusion - 1000 mg/m\^2 of gemcitabine followed by a 125 mg/m\^2 of abraxane. Prior to each gemcitabine infusion, subjects were pre-medicated with an FDA-approved anti-emetic (anti-nausea medication) in an effort to prevent nausea, at the discretion of the study physician.
Hydroxychloroquine oral capsules taken once or twice a daily at a dose of 1200mg. The first dose of hydroxychloroquine taken on Day 1 (48 hours before the first infusion of gemcitabine/abraxane), and continued daily until one day before surgery.
|
|---|---|---|
|
CT Tumor Size
|
2.562069 centimeters
Standard Deviation 1.105962
|
2.543056 centimeters
Standard Deviation 1.139370
|
PRIMARY outcome
Timeframe: Baseline - At the time of diagnosis, prior to treatmentPopulation: Patients who went to surgery and were evaluable for Evans Grade Histopathologic Response.
The number of participants in cancer diagnosis stage groups. Stage 0: cancer hasn't spread to nearby tissues/located in the same of origin.Stage I: cancers hasn't grown deeply into nearby tissues or spread to lymph nodes or other parts of the body. Stage II and III: cancers have grown more deeply into nearby tissues (may have metastasized to lymph nodes but not other parts of the body). Stage IV: most advanced stage (metastatic cancer) ; cancer has spread to other parts of the body. Stages subdivided further into the categories "A" (less agressive disease) and "B" (more advanced cancer). Example: stage IIA is less aggressive than stage IIB, but stage IIIA is more aggressive than stage IIB. (Stage variable used in the proportional odds logistic regression, secondary analysis of Evans Grade).
Outcome measures
| Measure |
Gemcitabine + Abraxane
n=30 Participants
Gemcitabine and Abraxane administered as an intravenous infusion on Study Days 3, 10, 17, 31, 38, and 45. Day 3 dosing: 1 hour infusion - 1000 mg/m\^2 of gemcitabine followed by a 125 mg/m\^2 of abraxane. Prior to each gemcitabine infusion, subjects were pre-medicated with an FDA-approved anti-emetic (anti-nausea medication) in an effort to prevent nausea, at the discretion of the study physician.
|
Gemcitabine + Abraxane and Hydroxychloroquine
n=41 Participants
Gemcitabine and Abraxane administered as an intravenous infusion on Study Days 3, 10, 17, 31, 38, and 45. Day 3 dosing: 1 hour infusion - 1000 mg/m\^2 of gemcitabine followed by a 125 mg/m\^2 of abraxane. Prior to each gemcitabine infusion, subjects were pre-medicated with an FDA-approved anti-emetic (anti-nausea medication) in an effort to prevent nausea, at the discretion of the study physician.
Hydroxychloroquine oral capsules taken once or twice a daily at a dose of 1200mg. The first dose of hydroxychloroquine taken on Day 1 (48 hours before the first infusion of gemcitabine/abraxane), and continued daily until one day before surgery.
|
|---|---|---|
|
Cancer Diagnosis Stage
IA
|
0 Participants
|
2 Participants
|
|
Cancer Diagnosis Stage
IB
|
5 Participants
|
1 Participants
|
|
Cancer Diagnosis Stage
IIA
|
6 Participants
|
11 Participants
|
|
Cancer Diagnosis Stage
IIB
|
19 Participants
|
20 Participants
|
|
Cancer Diagnosis Stage
Not Available
|
0 Participants
|
7 Participants
|
PRIMARY outcome
Timeframe: At the time of surgery (≥2 weeks and ≤6 weeks post chemotherapy)Population: Patients who went to surgery and were evaluable for Evans Grade Histopathologic Response.
The number of participants in having each type of surgical resection procedure: Celiac Axis Resection With Distal Pancreatectomy (DPCAR) (Modified Appleby), Distal Pancreatectomy, Total Pancreatectomy, or Whipple. (Operation variable used in the proportional odds logistic regression, secondary analysis of Evans Grade).
Outcome measures
| Measure |
Gemcitabine + Abraxane
n=30 Participants
Gemcitabine and Abraxane administered as an intravenous infusion on Study Days 3, 10, 17, 31, 38, and 45. Day 3 dosing: 1 hour infusion - 1000 mg/m\^2 of gemcitabine followed by a 125 mg/m\^2 of abraxane. Prior to each gemcitabine infusion, subjects were pre-medicated with an FDA-approved anti-emetic (anti-nausea medication) in an effort to prevent nausea, at the discretion of the study physician.
|
Gemcitabine + Abraxane and Hydroxychloroquine
n=41 Participants
Gemcitabine and Abraxane administered as an intravenous infusion on Study Days 3, 10, 17, 31, 38, and 45. Day 3 dosing: 1 hour infusion - 1000 mg/m\^2 of gemcitabine followed by a 125 mg/m\^2 of abraxane. Prior to each gemcitabine infusion, subjects were pre-medicated with an FDA-approved anti-emetic (anti-nausea medication) in an effort to prevent nausea, at the discretion of the study physician.
Hydroxychloroquine oral capsules taken once or twice a daily at a dose of 1200mg. The first dose of hydroxychloroquine taken on Day 1 (48 hours before the first infusion of gemcitabine/abraxane), and continued daily until one day before surgery.
|
|---|---|---|
|
Type of Surgical Procedure (Operation)
DPCAR
|
2 Participants
|
0 Participants
|
|
Type of Surgical Procedure (Operation)
Distal Pancreatectomy
|
3 Participants
|
5 Participants
|
|
Type of Surgical Procedure (Operation)
Total Pancreatectomy
|
1 Participants
|
0 Participants
|
|
Type of Surgical Procedure (Operation)
Whipple
|
24 Participants
|
36 Participants
|
PRIMARY outcome
Timeframe: At the time of surgery (≥2 weeks and ≤6 weeks post chemotherapy)Population: Patients who went to surgery and were evaluable for Evans Grade Histopathologic Response.
The number of participants who had robotic resection surgery. (Robotic surgery variable used in the proportional odds logistic regression, secondary analysis of Evans Grade).
Outcome measures
| Measure |
Gemcitabine + Abraxane
n=30 Participants
Gemcitabine and Abraxane administered as an intravenous infusion on Study Days 3, 10, 17, 31, 38, and 45. Day 3 dosing: 1 hour infusion - 1000 mg/m\^2 of gemcitabine followed by a 125 mg/m\^2 of abraxane. Prior to each gemcitabine infusion, subjects were pre-medicated with an FDA-approved anti-emetic (anti-nausea medication) in an effort to prevent nausea, at the discretion of the study physician.
|
Gemcitabine + Abraxane and Hydroxychloroquine
n=41 Participants
Gemcitabine and Abraxane administered as an intravenous infusion on Study Days 3, 10, 17, 31, 38, and 45. Day 3 dosing: 1 hour infusion - 1000 mg/m\^2 of gemcitabine followed by a 125 mg/m\^2 of abraxane. Prior to each gemcitabine infusion, subjects were pre-medicated with an FDA-approved anti-emetic (anti-nausea medication) in an effort to prevent nausea, at the discretion of the study physician.
Hydroxychloroquine oral capsules taken once or twice a daily at a dose of 1200mg. The first dose of hydroxychloroquine taken on Day 1 (48 hours before the first infusion of gemcitabine/abraxane), and continued daily until one day before surgery.
|
|---|---|---|
|
Robotic Resection Surgery
Yes - robotic surgical resection procedure
|
8 Participants
|
10 Participants
|
|
Robotic Resection Surgery
No - not robotic surgical resection procedure
|
22 Participants
|
31 Participants
|
PRIMARY outcome
Timeframe: Prior to treatmentPopulation: Patients who went to surgery and were evaluable for Evans Grade Histopathologic Response.
The Charlson Comorbidity Index is a method of categorizing comorbidities of patients based on the International Classification of Diseases (ICD) diagnosis codes found in administrative data, such as hospital abstracts data. Each comorbidity category has an associated weight (from 1 to 6), based on the adjusted risk of mortality or resource use, and the sum of all the weights results in a single comorbidity score for a patient. A score of zero indicates that no comorbidities were found. The higher the score, the more likely the predicted outcome will result in mortality or higher resource use. Up to 12 comorbidities with various weightings can result in a maximum score of 24. The minimum score is zero.
Outcome measures
| Measure |
Gemcitabine + Abraxane
n=30 Participants
Gemcitabine and Abraxane administered as an intravenous infusion on Study Days 3, 10, 17, 31, 38, and 45. Day 3 dosing: 1 hour infusion - 1000 mg/m\^2 of gemcitabine followed by a 125 mg/m\^2 of abraxane. Prior to each gemcitabine infusion, subjects were pre-medicated with an FDA-approved anti-emetic (anti-nausea medication) in an effort to prevent nausea, at the discretion of the study physician.
|
Gemcitabine + Abraxane and Hydroxychloroquine
n=41 Participants
Gemcitabine and Abraxane administered as an intravenous infusion on Study Days 3, 10, 17, 31, 38, and 45. Day 3 dosing: 1 hour infusion - 1000 mg/m\^2 of gemcitabine followed by a 125 mg/m\^2 of abraxane. Prior to each gemcitabine infusion, subjects were pre-medicated with an FDA-approved anti-emetic (anti-nausea medication) in an effort to prevent nausea, at the discretion of the study physician.
Hydroxychloroquine oral capsules taken once or twice a daily at a dose of 1200mg. The first dose of hydroxychloroquine taken on Day 1 (48 hours before the first infusion of gemcitabine/abraxane), and continued daily until one day before surgery.
|
|---|---|---|
|
Age-Adjusted Charlson Comorbidity Index
Age-Adjusted CCI=2
|
3 Participants
|
1 Participants
|
|
Age-Adjusted Charlson Comorbidity Index
Age-Adjusted CCI=3
|
5 Participants
|
2 Participants
|
|
Age-Adjusted Charlson Comorbidity Index
Age-Adjusted CCI=4
|
7 Participants
|
11 Participants
|
|
Age-Adjusted Charlson Comorbidity Index
Age-Adjusted CCI=5
|
8 Participants
|
15 Participants
|
|
Age-Adjusted Charlson Comorbidity Index
Age-Adjusted CCI=6
|
5 Participants
|
8 Participants
|
|
Age-Adjusted Charlson Comorbidity Index
Age-Adjusted CCI=7
|
2 Participants
|
2 Participants
|
|
Age-Adjusted Charlson Comorbidity Index
Age-Adjusted CCI=8
|
0 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: Prior to treatment (average 73.3 +/- 9.9 days prior to surgery)Population: Participants that were assigned to treatment and did not withdraw consent prior to being given drug.
Levels of Carbohydrate antigen 19-9 (CA19-9) response to pre-operative gemcitabine/ nab-paclitaxel measured in the serum (original scale)
Outcome measures
| Measure |
Gemcitabine + Abraxane
n=30 Participants
Gemcitabine and Abraxane administered as an intravenous infusion on Study Days 3, 10, 17, 31, 38, and 45. Day 3 dosing: 1 hour infusion - 1000 mg/m\^2 of gemcitabine followed by a 125 mg/m\^2 of abraxane. Prior to each gemcitabine infusion, subjects were pre-medicated with an FDA-approved anti-emetic (anti-nausea medication) in an effort to prevent nausea, at the discretion of the study physician.
|
Gemcitabine + Abraxane and Hydroxychloroquine
n=41 Participants
Gemcitabine and Abraxane administered as an intravenous infusion on Study Days 3, 10, 17, 31, 38, and 45. Day 3 dosing: 1 hour infusion - 1000 mg/m\^2 of gemcitabine followed by a 125 mg/m\^2 of abraxane. Prior to each gemcitabine infusion, subjects were pre-medicated with an FDA-approved anti-emetic (anti-nausea medication) in an effort to prevent nausea, at the discretion of the study physician.
Hydroxychloroquine oral capsules taken once or twice a daily at a dose of 1200mg. The first dose of hydroxychloroquine taken on Day 1 (48 hours before the first infusion of gemcitabine/abraxane), and continued daily until one day before surgery.
|
|---|---|---|
|
Carbohydrate Antigen 19-9 (CA19-9) Response
|
351.820 units per milliliter (U/mL)
Standard Deviation 839.925
|
1534.633 units per milliliter (U/mL)
Standard Deviation 3558.1212
|
SECONDARY outcome
Timeframe: After treatment (50-67 days post treatment/surgery)Population: Participants that were assigned to treatment and did not withdraw consent prior to being given drug.
Levels of Carbohydrate antigen 19-9 (CA19-9) response to pre-operative gemcitabine/ nab-paclitaxel measured in the serum (original scale).
Outcome measures
| Measure |
Gemcitabine + Abraxane
n=29 Participants
Gemcitabine and Abraxane administered as an intravenous infusion on Study Days 3, 10, 17, 31, 38, and 45. Day 3 dosing: 1 hour infusion - 1000 mg/m\^2 of gemcitabine followed by a 125 mg/m\^2 of abraxane. Prior to each gemcitabine infusion, subjects were pre-medicated with an FDA-approved anti-emetic (anti-nausea medication) in an effort to prevent nausea, at the discretion of the study physician.
|
Gemcitabine + Abraxane and Hydroxychloroquine
n=41 Participants
Gemcitabine and Abraxane administered as an intravenous infusion on Study Days 3, 10, 17, 31, 38, and 45. Day 3 dosing: 1 hour infusion - 1000 mg/m\^2 of gemcitabine followed by a 125 mg/m\^2 of abraxane. Prior to each gemcitabine infusion, subjects were pre-medicated with an FDA-approved anti-emetic (anti-nausea medication) in an effort to prevent nausea, at the discretion of the study physician.
Hydroxychloroquine oral capsules taken once or twice a daily at a dose of 1200mg. The first dose of hydroxychloroquine taken on Day 1 (48 hours before the first infusion of gemcitabine/abraxane), and continued daily until one day before surgery.
|
|---|---|---|
|
Carbohydrate Antigen 19-9 (CA19-9) Response
|
319.079 units per milliliter (U/mL)
Standard Deviation 1338.259
|
1696.710 units per milliliter (U/mL)
Standard Deviation 9850.273
|
SECONDARY outcome
Timeframe: At the time of surgery (≥2 weeks and ≤6 weeks post chemotherapy)Population: Participants that were assigned to treatment and did not withdraw consent prior to being given drug.
The proportion of participants with positive (disease) lymph nodes involvement.
Outcome measures
| Measure |
Gemcitabine + Abraxane
n=30 Participants
Gemcitabine and Abraxane administered as an intravenous infusion on Study Days 3, 10, 17, 31, 38, and 45. Day 3 dosing: 1 hour infusion - 1000 mg/m\^2 of gemcitabine followed by a 125 mg/m\^2 of abraxane. Prior to each gemcitabine infusion, subjects were pre-medicated with an FDA-approved anti-emetic (anti-nausea medication) in an effort to prevent nausea, at the discretion of the study physician.
|
Gemcitabine + Abraxane and Hydroxychloroquine
n=41 Participants
Gemcitabine and Abraxane administered as an intravenous infusion on Study Days 3, 10, 17, 31, 38, and 45. Day 3 dosing: 1 hour infusion - 1000 mg/m\^2 of gemcitabine followed by a 125 mg/m\^2 of abraxane. Prior to each gemcitabine infusion, subjects were pre-medicated with an FDA-approved anti-emetic (anti-nausea medication) in an effort to prevent nausea, at the discretion of the study physician.
Hydroxychloroquine oral capsules taken once or twice a daily at a dose of 1200mg. The first dose of hydroxychloroquine taken on Day 1 (48 hours before the first infusion of gemcitabine/abraxane), and continued daily until one day before surgery.
|
|---|---|---|
|
Positive Lymph Node Involvement
|
0.8 proportion of participants
Interval 0.614 to 0.923
|
0.561 proportion of participants
Interval 0.397 to 0.715
|
SECONDARY outcome
Timeframe: At the time of surgery (≥2 weeks and ≤6 weeks post chemotherapy)Population: Participants that were assigned to treatment and did not withdraw consent prior to being given drug.
The proportion of participants having resection for cure or complete remission, in which the surgical margins are negative for tumor cells. R0 resection indicates a microscopically margin-negative resection, in which no gross or microscopic tumor remains in the primary tumor bed.
Outcome measures
| Measure |
Gemcitabine + Abraxane
n=30 Participants
Gemcitabine and Abraxane administered as an intravenous infusion on Study Days 3, 10, 17, 31, 38, and 45. Day 3 dosing: 1 hour infusion - 1000 mg/m\^2 of gemcitabine followed by a 125 mg/m\^2 of abraxane. Prior to each gemcitabine infusion, subjects were pre-medicated with an FDA-approved anti-emetic (anti-nausea medication) in an effort to prevent nausea, at the discretion of the study physician.
|
Gemcitabine + Abraxane and Hydroxychloroquine
n=41 Participants
Gemcitabine and Abraxane administered as an intravenous infusion on Study Days 3, 10, 17, 31, 38, and 45. Day 3 dosing: 1 hour infusion - 1000 mg/m\^2 of gemcitabine followed by a 125 mg/m\^2 of abraxane. Prior to each gemcitabine infusion, subjects were pre-medicated with an FDA-approved anti-emetic (anti-nausea medication) in an effort to prevent nausea, at the discretion of the study physician.
Hydroxychloroquine oral capsules taken once or twice a daily at a dose of 1200mg. The first dose of hydroxychloroquine taken on Day 1 (48 hours before the first infusion of gemcitabine/abraxane), and continued daily until one day before surgery.
|
|---|---|---|
|
Rate of R0 Resection
|
0.7 proportion of participants
Interval 0.506 to 0.853
|
0.829 proportion of participants
Interval 0.679 to 0.928
|
Adverse Events
Gemcitabine + Abraxane
Serious events: 30 serious events
Other events: 43 other events
Deaths: 28 deaths
Gemcitabine + Abraxane and Hydroxychloroquine
Serious events: 39 serious events
Other events: 60 other events
Deaths: 34 deaths
Serious adverse events
| Measure |
Gemcitabine + Abraxane
n=43 participants at risk
Gemcitabine and Abraxane administered as an intravenous infusion on Study Days 3, 10, 17, 31, 38, and 45. Day 3 dosing: 1 hour infusion - 1000 mg/m\^2 of gemcitabine followed by a 125 mg/m\^2 of abraxane. Prior to each gemcitabine infusion, subjects were pre-medicated with an FDA-approved anti-emetic (anti-nausea medication) in an effort to prevent nausea, at the discretion of the study physician.
|
Gemcitabine + Abraxane and Hydroxychloroquine
n=61 participants at risk
Gemcitabine and Abraxane administered as an intravenous infusion on Study Days 3, 10, 17, 31, 38, and 45. Day 3 dosing: 1 hour infusion - 1000 mg/m\^2 of gemcitabine followed by a 125 mg/m\^2 of abraxane. Prior to each gemcitabine infusion, subjects were pre-medicated with an FDA-approved anti-emetic (anti-nausea medication) in an effort to prevent nausea, at the discretion of the study physician.
Hydroxychloroquine oral capsules taken once or twice a daily at a dose of 1200mg. The first dose of hydroxychloroquine taken on Day 1 (48 hours before the first infusion of gemcitabine/abraxane), and continued daily until one day before surgery.
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/43 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Renal and urinary disorders
Acute kidney injury
|
0.00%
0/43 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Investigations
Alanine aminotransferase increased
|
2.3%
1/43 • Number of events 2 • Up to 4 years
|
9.8%
6/61 • Number of events 21 • Up to 4 years
|
|
Investigations
Alkaline phosphatase increased
|
2.3%
1/43 • Number of events 2 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Immune system disorders
Allergic reaction
|
2.3%
1/43 • Number of events 2 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Blood and lymphatic system disorders
Anemia
|
9.3%
4/43 • Number of events 9 • Up to 4 years
|
4.9%
3/61 • Number of events 9 • Up to 4 years
|
|
Investigations
Aspartate aminotransferase increased
|
4.7%
2/43 • Number of events 4 • Up to 4 years
|
6.6%
4/61 • Number of events 12 • Up to 4 years
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/43 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Investigations
Blood bilirubin increased
|
2.3%
1/43 • Number of events 2 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.00%
0/43 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Infections and infestations
Catheter related infection
|
2.3%
1/43 • Number of events 2 • Up to 4 years
|
0.00%
0/61 • Up to 4 years
|
|
Hepatobiliary disorders
Cholecystitis
|
0.00%
0/43 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Metabolism and nutrition disorders
Dehydration
|
2.3%
1/43 • Number of events 2 • Up to 4 years
|
8.2%
5/61 • Number of events 21 • Up to 4 years
|
|
Gastrointestinal disorders
Diarrhea
|
2.3%
1/43 • Number of events 2 • Up to 4 years
|
4.9%
3/61 • Number of events 13 • Up to 4 years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.00%
0/43 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
General disorders
Edema limbs
|
0.00%
0/43 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
General disorders
Fatigue
|
4.7%
2/43 • Number of events 4 • Up to 4 years
|
8.2%
5/61 • Number of events 18 • Up to 4 years
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
14.0%
6/43 • Number of events 20 • Up to 4 years
|
3.3%
2/61 • Number of events 6 • Up to 4 years
|
|
General disorders
Fever
|
2.3%
1/43 • Number of events 2 • Up to 4 years
|
0.00%
0/61 • Up to 4 years
|
|
Gastrointestinal disorders
Gastrointestinal disorders - Other, specify
|
0.00%
0/43 • Up to 4 years
|
3.3%
2/61 • Number of events 6 • Up to 4 years
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
0.00%
0/43 • Up to 4 years
|
4.9%
3/61 • Number of events 9 • Up to 4 years
|
|
Hepatobiliary disorders
Hepatobiliary disorders - Other, specify
|
0.00%
0/43 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
2.3%
1/43 • Number of events 5 • Up to 4 years
|
0.00%
0/61 • Up to 4 years
|
|
Vascular disorders
Hypertension
|
9.3%
4/43 • Number of events 10 • Up to 4 years
|
4.9%
3/61 • Number of events 9 • Up to 4 years
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
0.00%
0/43 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Metabolism and nutrition disorders
Hyponatremia
|
4.7%
2/43 • Number of events 3 • Up to 4 years
|
9.8%
6/61 • Number of events 24 • Up to 4 years
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
0.00%
0/43 • Up to 4 years
|
3.3%
2/61 • Number of events 6 • Up to 4 years
|
|
Vascular disorders
Hypotension
|
0.00%
0/43 • Up to 4 years
|
3.3%
2/61 • Number of events 9 • Up to 4 years
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
2.3%
1/43 • Number of events 2 • Up to 4 years
|
0.00%
0/61 • Up to 4 years
|
|
Infections and infestations
Infections and infestations - Other, specify
|
7.0%
3/43 • Number of events 6 • Up to 4 years
|
0.00%
0/61 • Up to 4 years
|
|
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications - Other, specify
|
0.00%
0/43 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Investigations
Lipase increased
|
0.00%
0/43 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Infections and infestations
Lung infection
|
4.7%
2/43 • Number of events 4 • Up to 4 years
|
0.00%
0/61 • Up to 4 years
|
|
Investigations
Lymphocyte count decreased
|
0.00%
0/43 • Up to 4 years
|
4.9%
3/61 • Number of events 9 • Up to 4 years
|
|
Metabolism and nutrition disorders
Metabolism and nutrition disorders - Other, specify
|
2.3%
1/43 • Number of events 2 • Up to 4 years
|
0.00%
0/61 • Up to 4 years
|
|
General disorders
Multi-organ failure
|
2.3%
1/43 • Number of events 3 • Up to 4 years
|
0.00%
0/61 • Up to 4 years
|
|
Gastrointestinal disorders
Nausea
|
2.3%
1/43 • Number of events 2 • Up to 4 years
|
4.9%
3/61 • Number of events 12 • Up to 4 years
|
|
Investigations
Neutrophil count decreased
|
23.3%
10/43 • Number of events 30 • Up to 4 years
|
18.0%
11/61 • Number of events 45 • Up to 4 years
|
|
General disorders
Pain
|
2.3%
1/43 • Number of events 3 • Up to 4 years
|
0.00%
0/61 • Up to 4 years
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/43 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Investigations
Platelet count decreased
|
7.0%
3/43 • Number of events 6 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
2.3%
1/43 • Number of events 2 • Up to 4 years
|
0.00%
0/61 • Up to 4 years
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
4.7%
2/43 • Number of events 5 • Up to 4 years
|
0.00%
0/61 • Up to 4 years
|
|
Infections and infestations
Skin infection
|
7.0%
3/43 • Number of events 12 • Up to 4 years
|
0.00%
0/61 • Up to 4 years
|
|
Vascular disorders
Thromboembolic event
|
2.3%
1/43 • Number of events 3 • Up to 4 years
|
1.6%
1/61 • Number of events 4 • Up to 4 years
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/43 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Cardiac disorders
Ventricular fibrillation
|
2.3%
1/43 • Number of events 3 • Up to 4 years
|
0.00%
0/61 • Up to 4 years
|
|
Gastrointestinal disorders
Vomiting
|
2.3%
1/43 • Number of events 2 • Up to 4 years
|
3.3%
2/61 • Number of events 6 • Up to 4 years
|
|
Investigations
White blood cell decreased
|
14.0%
6/43 • Number of events 12 • Up to 4 years
|
16.4%
10/61 • Number of events 39 • Up to 4 years
|
|
Infections and infestations
Wound infection
|
4.7%
2/43 • Number of events 5 • Up to 4 years
|
0.00%
0/61 • Up to 4 years
|
Other adverse events
| Measure |
Gemcitabine + Abraxane
n=43 participants at risk
Gemcitabine and Abraxane administered as an intravenous infusion on Study Days 3, 10, 17, 31, 38, and 45. Day 3 dosing: 1 hour infusion - 1000 mg/m\^2 of gemcitabine followed by a 125 mg/m\^2 of abraxane. Prior to each gemcitabine infusion, subjects were pre-medicated with an FDA-approved anti-emetic (anti-nausea medication) in an effort to prevent nausea, at the discretion of the study physician.
|
Gemcitabine + Abraxane and Hydroxychloroquine
n=61 participants at risk
Gemcitabine and Abraxane administered as an intravenous infusion on Study Days 3, 10, 17, 31, 38, and 45. Day 3 dosing: 1 hour infusion - 1000 mg/m\^2 of gemcitabine followed by a 125 mg/m\^2 of abraxane. Prior to each gemcitabine infusion, subjects were pre-medicated with an FDA-approved anti-emetic (anti-nausea medication) in an effort to prevent nausea, at the discretion of the study physician.
Hydroxychloroquine oral capsules taken once or twice a daily at a dose of 1200mg. The first dose of hydroxychloroquine taken on Day 1 (48 hours before the first infusion of gemcitabine/abraxane), and continued daily until one day before surgery.
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
11.6%
5/43 • Number of events 10 • Up to 4 years
|
13.1%
8/61 • Number of events 24 • Up to 4 years
|
|
Investigations
Activated partial thromboplastin time prolonged
|
2.3%
1/43 • Number of events 1 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Renal and urinary disorders
Acute kidney injury
|
0.00%
0/43 • Up to 4 years
|
3.3%
2/61 • Number of events 6 • Up to 4 years
|
|
Investigations
Alanine aminotransferase increased
|
41.9%
18/43 • Number of events 56 • Up to 4 years
|
52.5%
32/61 • Number of events 147 • Up to 4 years
|
|
Investigations
Alkaline phosphatase increased
|
25.6%
11/43 • Number of events 27 • Up to 4 years
|
37.7%
23/61 • Number of events 105 • Up to 4 years
|
|
Immune system disorders
Allergic reaction
|
2.3%
1/43 • Number of events 4 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis
|
2.3%
1/43 • Number of events 2 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
7.0%
3/43 • Number of events 6 • Up to 4 years
|
16.4%
10/61 • Number of events 39 • Up to 4 years
|
|
Blood and lymphatic system disorders
Anemia
|
83.7%
36/43 • Number of events 151 • Up to 4 years
|
82.0%
50/61 • Number of events 333 • Up to 4 years
|
|
Metabolism and nutrition disorders
Anorexia
|
11.6%
5/43 • Number of events 10 • Up to 4 years
|
19.7%
12/61 • Number of events 39 • Up to 4 years
|
|
Psychiatric disorders
Anxiety
|
9.3%
4/43 • Number of events 8 • Up to 4 years
|
4.9%
3/61 • Number of events 9 • Up to 4 years
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
2.3%
1/43 • Number of events 2 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Investigations
Aspartate aminotransferase increased
|
39.5%
17/43 • Number of events 51 • Up to 4 years
|
59.0%
36/61 • Number of events 135 • Up to 4 years
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/43 • Up to 4 years
|
3.3%
2/61 • Number of events 6 • Up to 4 years
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
7.0%
3/43 • Number of events 6 • Up to 4 years
|
4.9%
3/61 • Number of events 9 • Up to 4 years
|
|
Gastrointestinal disorders
Bloating
|
0.00%
0/43 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Investigations
Blood bilirubin increased
|
7.0%
3/43 • Number of events 8 • Up to 4 years
|
11.5%
7/61 • Number of events 27 • Up to 4 years
|
|
Eye disorders
Blurred vision
|
0.00%
0/43 • Up to 4 years
|
3.3%
2/61 • Number of events 9 • Up to 4 years
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.00%
0/43 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Investigations
CPK increased
|
0.00%
0/43 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Cardiac disorders
Cardiac disorders - Other, specify
|
2.3%
1/43 • Number of events 2 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Infections and infestations
Catheter related infection
|
2.3%
1/43 • Number of events 2 • Up to 4 years
|
0.00%
0/61 • Up to 4 years
|
|
Cardiac disorders
Chest pain - cardiac
|
0.00%
0/43 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
General disorders
Chills
|
4.7%
2/43 • Number of events 5 • Up to 4 years
|
6.6%
4/61 • Number of events 13 • Up to 4 years
|
|
Hepatobiliary disorders
Cholecystitis
|
0.00%
0/43 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Psychiatric disorders
Confusion
|
2.3%
1/43 • Number of events 2 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Gastrointestinal disorders
Constipation
|
23.3%
10/43 • Number of events 26 • Up to 4 years
|
21.3%
13/61 • Number of events 42 • Up to 4 years
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
7.0%
3/43 • Number of events 6 • Up to 4 years
|
3.3%
2/61 • Number of events 6 • Up to 4 years
|
|
Investigations
Creatinine increased
|
9.3%
4/43 • Number of events 8 • Up to 4 years
|
6.6%
4/61 • Number of events 12 • Up to 4 years
|
|
Metabolism and nutrition disorders
Dehydration
|
9.3%
4/43 • Number of events 9 • Up to 4 years
|
14.8%
9/61 • Number of events 36 • Up to 4 years
|
|
Psychiatric disorders
Depression
|
2.3%
1/43 • Number of events 2 • Up to 4 years
|
3.3%
2/61 • Number of events 6 • Up to 4 years
|
|
Gastrointestinal disorders
Diarrhea
|
25.6%
11/43 • Number of events 27 • Up to 4 years
|
41.0%
25/61 • Number of events 100 • Up to 4 years
|
|
Nervous system disorders
Dizziness
|
2.3%
1/43 • Number of events 3 • Up to 4 years
|
4.9%
3/61 • Number of events 9 • Up to 4 years
|
|
Gastrointestinal disorders
Dry mouth
|
2.3%
1/43 • Number of events 2 • Up to 4 years
|
0.00%
0/61 • Up to 4 years
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
0.00%
0/43 • Up to 4 years
|
4.9%
3/61 • Number of events 9 • Up to 4 years
|
|
Nervous system disorders
Dysgeusia
|
2.3%
1/43 • Number of events 2 • Up to 4 years
|
3.3%
2/61 • Number of events 9 • Up to 4 years
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/43 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
2.3%
1/43 • Number of events 2 • Up to 4 years
|
8.2%
5/61 • Number of events 18 • Up to 4 years
|
|
General disorders
Edema limbs
|
18.6%
8/43 • Number of events 18 • Up to 4 years
|
11.5%
7/61 • Number of events 21 • Up to 4 years
|
|
General disorders
Edema trunk
|
2.3%
1/43 • Number of events 2 • Up to 4 years
|
0.00%
0/61 • Up to 4 years
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
4.7%
2/43 • Number of events 5 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Skin and subcutaneous tissue disorders
Erythema multiforme
|
0.00%
0/43 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Gastrointestinal disorders
Esophageal pain
|
2.3%
1/43 • Number of events 2 • Up to 4 years
|
0.00%
0/61 • Up to 4 years
|
|
Eye disorders
Eye disorders - Other, specify
|
2.3%
1/43 • Number of events 2 • Up to 4 years
|
0.00%
0/61 • Up to 4 years
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/43 • Up to 4 years
|
3.3%
2/61 • Number of events 6 • Up to 4 years
|
|
General disorders
Fatigue
|
67.4%
29/43 • Number of events 86 • Up to 4 years
|
44.3%
27/61 • Number of events 141 • Up to 4 years
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
14.0%
6/43 • Number of events 28 • Up to 4 years
|
11.5%
7/61 • Number of events 27 • Up to 4 years
|
|
General disorders
Fever
|
14.0%
6/43 • Number of events 16 • Up to 4 years
|
13.1%
8/61 • Number of events 28 • Up to 4 years
|
|
Gastrointestinal disorders
Flatulence
|
7.0%
3/43 • Number of events 10 • Up to 4 years
|
8.2%
5/61 • Number of events 15 • Up to 4 years
|
|
General disorders
Flu like symptoms
|
2.3%
1/43 • Number of events 2 • Up to 4 years
|
6.6%
4/61 • Number of events 12 • Up to 4 years
|
|
Vascular disorders
Flushing
|
0.00%
0/43 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
7.0%
3/43 • Number of events 6 • Up to 4 years
|
6.6%
4/61 • Number of events 15 • Up to 4 years
|
|
Gastrointestinal disorders
Gastrointestinal disorders - Other, specify
|
4.7%
2/43 • Number of events 4 • Up to 4 years
|
11.5%
7/61 • Number of events 24 • Up to 4 years
|
|
General disorders
General disorders and administration site conditions - Other, specify
|
11.6%
5/43 • Number of events 20 • Up to 4 years
|
11.5%
7/61 • Number of events 24 • Up to 4 years
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
0.00%
0/43 • Up to 4 years
|
16.4%
10/61 • Number of events 57 • Up to 4 years
|
|
Gastrointestinal disorders
Gingival pain
|
0.00%
0/43 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Nervous system disorders
Headache
|
2.3%
1/43 • Number of events 2 • Up to 4 years
|
4.9%
3/61 • Number of events 9 • Up to 4 years
|
|
Vascular disorders
Hematoma
|
2.3%
1/43 • Number of events 2 • Up to 4 years
|
0.00%
0/61 • Up to 4 years
|
|
Renal and urinary disorders
Hematuria
|
0.00%
0/43 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Investigations
Hemoglobin increased
|
2.3%
1/43 • Number of events 2 • Up to 4 years
|
0.00%
0/61 • Up to 4 years
|
|
Gastrointestinal disorders
Hemorrhoids
|
0.00%
0/43 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Hepatobiliary disorders
Hepatobiliary disorders - Other, specify
|
0.00%
0/43 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
0.00%
0/43 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Vascular disorders
Hot flashes
|
0.00%
0/43 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
2.3%
1/43 • Number of events 3 • Up to 4 years
|
4.9%
3/61 • Number of events 9 • Up to 4 years
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
11.6%
5/43 • Number of events 30 • Up to 4 years
|
4.9%
3/61 • Number of events 9 • Up to 4 years
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
4.7%
2/43 • Number of events 4 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Metabolism and nutrition disorders
Hypernatremia
|
4.7%
2/43 • Number of events 5 • Up to 4 years
|
3.3%
2/61 • Number of events 6 • Up to 4 years
|
|
Vascular disorders
Hypertension
|
30.2%
13/43 • Number of events 59 • Up to 4 years
|
23.0%
14/61 • Number of events 60 • Up to 4 years
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
58.1%
25/43 • Number of events 92 • Up to 4 years
|
65.6%
40/61 • Number of events 204 • Up to 4 years
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
2.3%
1/43 • Number of events 4 • Up to 4 years
|
9.8%
6/61 • Number of events 30 • Up to 4 years
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
2.3%
1/43 • Number of events 2 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Metabolism and nutrition disorders
Hypokalemia
|
25.6%
11/43 • Number of events 33 • Up to 4 years
|
32.8%
20/61 • Number of events 81 • Up to 4 years
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
0.00%
0/43 • Up to 4 years
|
4.9%
3/61 • Number of events 9 • Up to 4 years
|
|
Metabolism and nutrition disorders
Hyponatremia
|
39.5%
17/43 • Number of events 53 • Up to 4 years
|
45.9%
28/61 • Number of events 150 • Up to 4 years
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
2.3%
1/43 • Number of events 3 • Up to 4 years
|
6.6%
4/61 • Number of events 24 • Up to 4 years
|
|
Vascular disorders
Hypotension
|
2.3%
1/43 • Number of events 2 • Up to 4 years
|
14.8%
9/61 • Number of events 33 • Up to 4 years
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
4.7%
2/43 • Number of events 4 • Up to 4 years
|
0.00%
0/61 • Up to 4 years
|
|
Investigations
INR increased
|
2.3%
1/43 • Number of events 1 • Up to 4 years
|
0.00%
0/61 • Up to 4 years
|
|
Infections and infestations
Infections and infestations - Other, specify
|
7.0%
3/43 • Number of events 8 • Up to 4 years
|
3.3%
2/61 • Number of events 6 • Up to 4 years
|
|
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications - Other, specify
|
0.00%
0/43 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Psychiatric disorders
Insomnia
|
2.3%
1/43 • Number of events 2 • Up to 4 years
|
8.2%
5/61 • Number of events 15 • Up to 4 years
|
|
Investigations
Investigations - Other, specify
|
0.00%
0/43 • Up to 4 years
|
4.9%
3/61 • Number of events 9 • Up to 4 years
|
|
Investigations
Lipase increased
|
2.3%
1/43 • Number of events 3 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Infections and infestations
Lung infection
|
4.7%
2/43 • Number of events 4 • Up to 4 years
|
0.00%
0/61 • Up to 4 years
|
|
Investigations
Lymphocyte count decreased
|
30.2%
13/43 • Number of events 37 • Up to 4 years
|
21.3%
13/61 • Number of events 63 • Up to 4 years
|
|
Gastrointestinal disorders
Malabsorption
|
0.00%
0/43 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
General disorders
Malaise
|
2.3%
1/43 • Number of events 2 • Up to 4 years
|
4.9%
3/61 • Number of events 9 • Up to 4 years
|
|
Nervous system disorders
Memory impairment
|
2.3%
1/43 • Number of events 2 • Up to 4 years
|
0.00%
0/61 • Up to 4 years
|
|
Metabolism and nutrition disorders
Metabolism and nutrition disorders - Other, specify
|
4.7%
2/43 • Number of events 10 • Up to 4 years
|
8.2%
5/61 • Number of events 18 • Up to 4 years
|
|
Infections and infestations
Mucosal infection
|
2.3%
1/43 • Number of events 2 • Up to 4 years
|
0.00%
0/61 • Up to 4 years
|
|
Gastrointestinal disorders
Mucositis oral
|
4.7%
2/43 • Number of events 4 • Up to 4 years
|
3.3%
2/61 • Number of events 6 • Up to 4 years
|
|
General disorders
Multi-organ failure
|
2.3%
1/43 • Number of events 3 • Up to 4 years
|
0.00%
0/61 • Up to 4 years
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness lower limb
|
2.3%
1/43 • Number of events 2 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorder - Other, specify
|
4.7%
2/43 • Number of events 4 • Up to 4 years
|
3.3%
2/61 • Number of events 12 • Up to 4 years
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
4.7%
2/43 • Number of events 4 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Skin and subcutaneous tissue disorders
Nail discoloration
|
2.3%
1/43 • Number of events 2 • Up to 4 years
|
0.00%
0/61 • Up to 4 years
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
2.3%
1/43 • Number of events 2 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Gastrointestinal disorders
Nausea
|
27.9%
12/43 • Number of events 41 • Up to 4 years
|
50.8%
31/61 • Number of events 126 • Up to 4 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify
|
0.00%
0/43 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Nervous system disorders
Nervous system disorders - Other, specify
|
2.3%
1/43 • Number of events 2 • Up to 4 years
|
4.9%
3/61 • Number of events 12 • Up to 4 years
|
|
Investigations
Neutrophil count decreased
|
67.4%
29/43 • Number of events 123 • Up to 4 years
|
67.2%
41/61 • Number of events 198 • Up to 4 years
|
|
Gastrointestinal disorders
Oral pain
|
0.00%
0/43 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
General disorders
Pain
|
11.6%
5/43 • Number of events 15 • Up to 4 years
|
6.6%
4/61 • Number of events 12 • Up to 4 years
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/43 • Up to 4 years
|
4.9%
3/61 • Number of events 12 • Up to 4 years
|
|
Nervous system disorders
Paresthesia
|
0.00%
0/43 • Up to 4 years
|
1.6%
1/61 • Number of events 6 • Up to 4 years
|
|
Cardiac disorders
Paroxysmal atrial tachycardia
|
2.3%
1/43 • Number of events 2 • Up to 4 years
|
0.00%
0/61 • Up to 4 years
|
|
Nervous system disorders
Peripheral motor neuropathy
|
2.3%
1/43 • Number of events 2 • Up to 4 years
|
0.00%
0/61 • Up to 4 years
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
4.7%
2/43 • Number of events 6 • Up to 4 years
|
9.8%
6/61 • Number of events 24 • Up to 4 years
|
|
Vascular disorders
Phlebitis
|
0.00%
0/43 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Investigations
Platelet count decreased
|
69.8%
30/43 • Number of events 113 • Up to 4 years
|
73.8%
45/61 • Number of events 228 • Up to 4 years
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
2.3%
1/43 • Number of events 2 • Up to 4 years
|
0.00%
0/61 • Up to 4 years
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
4.7%
2/43 • Number of events 5 • Up to 4 years
|
0.00%
0/61 • Up to 4 years
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
2.3%
1/43 • Number of events 2 • Up to 4 years
|
3.3%
2/61 • Number of events 6 • Up to 4 years
|
|
Cardiac disorders
Pulmonary valve disease
|
0.00%
0/43 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
0.00%
0/43 • Up to 4 years
|
4.9%
3/61 • Number of events 9 • Up to 4 years
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
0.00%
0/43 • Up to 4 years
|
6.6%
4/61 • Number of events 12 • Up to 4 years
|
|
Gastrointestinal disorders
Rectal hemorrhage
|
2.3%
1/43 • Number of events 2 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Renal and urinary disorders
Renal and urinary disorders - Other, specify
|
2.3%
1/43 • Number of events 2 • Up to 4 years
|
0.00%
0/61 • Up to 4 years
|
|
Reproductive system and breast disorders
Reproductive system and breast disorders - Other, specify
|
0.00%
0/43 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders - Other, specify
|
7.0%
3/43 • Number of events 6 • Up to 4 years
|
9.8%
6/61 • Number of events 18 • Up to 4 years
|
|
Investigations
Serum amylase increased
|
0.00%
0/43 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Cardiac disorders
Sinus bradycardia
|
2.3%
1/43 • Number of events 4 • Up to 4 years
|
0.00%
0/61 • Up to 4 years
|
|
Cardiac disorders
Sinus tachycardia
|
2.3%
1/43 • Number of events 2 • Up to 4 years
|
3.3%
2/61 • Number of events 6 • Up to 4 years
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other, specify
|
4.7%
2/43 • Number of events 5 • Up to 4 years
|
13.1%
8/61 • Number of events 33 • Up to 4 years
|
|
Skin and subcutaneous tissue disorders
Skin hyperpigmentation
|
0.00%
0/43 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Infections and infestations
Skin infection
|
7.0%
3/43 • Number of events 20 • Up to 4 years
|
1.6%
1/61 • Number of events 6 • Up to 4 years
|
|
Nervous system disorders
Somnolence
|
0.00%
0/43 • Up to 4 years
|
1.6%
1/61 • Number of events 4 • Up to 4 years
|
|
Respiratory, thoracic and mediastinal disorders
Sore throat
|
0.00%
0/43 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Vascular disorders
Superficial thrombophlebitis
|
0.00%
0/43 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Cardiac disorders
Supraventricular tachycardia
|
0.00%
0/43 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Vascular disorders
Thromboembolic event
|
2.3%
1/43 • Number of events 5 • Up to 4 years
|
3.3%
2/61 • Number of events 7 • Up to 4 years
|
|
Infections and infestations
Tooth infection
|
0.00%
0/43 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/43 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Nervous system disorders
Tremor
|
0.00%
0/43 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Cardiac disorders
Tricuspid valve disease
|
0.00%
0/43 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Renal and urinary disorders
Urinary retention
|
0.00%
0/43 • Up to 4 years
|
3.3%
2/61 • Number of events 6 • Up to 4 years
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/43 • Up to 4 years
|
8.2%
5/61 • Number of events 18 • Up to 4 years
|
|
Renal and urinary disorders
Urinary tract obstruction
|
0.00%
0/43 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Vascular disorders
Vascular disorders - Other, specify
|
2.3%
1/43 • Number of events 2 • Up to 4 years
|
0.00%
0/61 • Up to 4 years
|
|
Cardiac disorders
Ventricular fibrillation
|
2.3%
1/43 • Number of events 3 • Up to 4 years
|
0.00%
0/61 • Up to 4 years
|
|
Cardiac disorders
Ventricular tachycardia
|
0.00%
0/43 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/43 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
|
Gastrointestinal disorders
Vomiting
|
14.0%
6/43 • Number of events 19 • Up to 4 years
|
26.2%
16/61 • Number of events 48 • Up to 4 years
|
|
Investigations
Weight loss
|
14.0%
6/43 • Number of events 12 • Up to 4 years
|
8.2%
5/61 • Number of events 18 • Up to 4 years
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
2.3%
1/43 • Number of events 2 • Up to 4 years
|
0.00%
0/61 • Up to 4 years
|
|
Investigations
White blood cell decreased
|
72.1%
31/43 • Number of events 122 • Up to 4 years
|
68.9%
42/61 • Number of events 237 • Up to 4 years
|
|
Infections and infestations
Wound infection
|
4.7%
2/43 • Number of events 5 • Up to 4 years
|
1.6%
1/61 • Number of events 3 • Up to 4 years
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place