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Randomized Phase II Trial of Pre-Operative Gemcitabine and Nab Paclitacel With or With Out Hydroxychloroquine

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: NCT01978184
Recruitment Status : Completed
First Posted : November 7, 2013
Results First Posted : March 27, 2019
Last Update Posted : March 27, 2019
Sponsor:
Information provided by (Responsible Party):
Nathan Bahary, MD, University of Pittsburgh

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Pancreatic Cancer
Interventions Drug: gemcitabine
Drug: abraxane
Drug: hydroxychloroquine
Enrollment 104
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Gemcitabine + Abraxane Gemcitabine + Abraxane and Hydroxychloroquine
Hide Arm/Group Description 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 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.

Period Title: Overall Study
Started 43 61
Completed 30 41
Not Completed 13 20
Reason Not Completed
Progressive disease             5             5
Other than PDA             2             2
Physician Decision             0             3
Noncompliance             1             2
Death             1             0
Withdrew- toxicities or physical decline             4             8
Arm/Group Title Gemcitabine + Abraxane Gemcitabine + Abraxane and Hydroxychloroquine Total
Hide Arm/Group Description 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 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 of all reporting groups
Overall Number of Baseline Participants 30 41 71
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 30 participants 41 participants 71 participants
63.6  (11.8) 66.1  (8.4) 65  (10)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants 41 participants 71 participants
Female
14
  46.7%
17
  41.5%
31
  43.7%
Male
16
  53.3%
24
  58.5%
40
  56.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants 41 participants 71 participants
Hispanic or Latino
0
   0.0%
1
   2.4%
1
   1.4%
Not Hispanic or Latino
30
 100.0%
40
  97.6%
70
  98.6%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants 41 participants 71 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
2
   4.9%
2
   2.8%
White
28
  93.3%
38
  92.7%
66
  93.0%
More than one race
1
   3.3%
0
   0.0%
1
   1.4%
Unknown or Not Reported
1
   3.3%
1
   2.4%
2
   2.8%
1.Primary Outcome
Title Evans Grade Histopathologic Response
Hide Description 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.
Time Frame Up to 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
Patients who went to surgery and were evaluable for Evans Grade Histopathologic Response.
Arm/Group Title Gemcitabine + Abraxane Gemcitabine + Abraxane and Hydroxychloroquine
Hide Arm/Group Description:
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 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 Number of Participants Analyzed 30 41
Measure Type: Number
Unit of Measure: number of participants
Evans grade - I 10 7
Evans grade - IIA 17 12
Evans grade - IIB 3 13
Evans grade - III 0 9
2.Primary Outcome
Title Age at Diagnosis
Hide Description 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).
Time Frame Baseline - At the time of diagnosis, prior to treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Patients who went to surgery and were evaluable for Evans Grade Histopathologic Response.
Arm/Group Title Gemcitabine + Abraxane Gemcitabine + Abraxane and Hydroxychloroquine
Hide Arm/Group Description:
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 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 Number of Participants Analyzed 30 41
Mean (Standard Deviation)
Unit of Measure: years
63.6  (11.8) 66.1  (8.4)
3.Primary Outcome
Title CT Tumor Size
Hide Description Tumor size as measured via computerized tomography (CT) scan (as a variable in the proportional odds logistic regression, secondary analysis of Evans Grade).
Time Frame Baseline - At the time of diagnosis, prior to treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Patients who went to surgery and were evaluable for Evans Grade Histopathologic Response.
Arm/Group Title Gemcitabine + Abraxane Gemcitabine + Abraxane and Hydroxychloroquine
Hide Arm/Group Description:
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 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 Number of Participants Analyzed 29 41
Mean (Standard Deviation)
Unit of Measure: centimeters
2.562069  (1.105962) 2.543056  (1.139370)
4.Primary Outcome
Title Cancer Diagnosis Stage
Hide Description 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).
Time Frame Baseline - At the time of diagnosis, prior to treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Patients who went to surgery and were evaluable for Evans Grade Histopathologic Response.
Arm/Group Title Gemcitabine + Abraxane Gemcitabine + Abraxane and Hydroxychloroquine
Hide Arm/Group Description:
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 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 Number of Participants Analyzed 30 41
Measure Type: Count of Participants
Unit of Measure: Participants
IA
0
   0.0%
2
   4.9%
IB
5
  16.7%
1
   2.4%
IIA
6
  20.0%
11
  26.8%
IIB
19
  63.3%
20
  48.8%
Not Available
0
   0.0%
7
  17.1%
5.Primary Outcome
Title Type of Surgical Procedure (Operation)
Hide Description 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).
Time Frame At the time of surgery (≥2 weeks and ≤6 weeks post chemotherapy)
Hide Outcome Measure Data
Hide Analysis Population Description
Patients who went to surgery and were evaluable for Evans Grade Histopathologic Response.
Arm/Group Title Gemcitabine + Abraxane Gemcitabine + Abraxane and Hydroxychloroquine
Hide Arm/Group Description:
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 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 Number of Participants Analyzed 30 41
Measure Type: Count of Participants
Unit of Measure: Participants
DPCAR
2
   6.7%
0
   0.0%
Distal Pancreatectomy
3
  10.0%
5
  12.2%
Total Pancreatectomy
1
   3.3%
0
   0.0%
Whipple
24
  80.0%
36
  87.8%
6.Primary Outcome
Title Robotic Resection Surgery
Hide Description The number of participants who had robotic resection surgery. (Robotic surgery variable used in the proportional odds logistic regression, secondary analysis of Evans Grade).
Time Frame At the time of surgery (≥2 weeks and ≤6 weeks post chemotherapy)
Hide Outcome Measure Data
Hide Analysis Population Description
Patients who went to surgery and were evaluable for Evans Grade Histopathologic Response.
Arm/Group Title Gemcitabine + Abraxane Gemcitabine + Abraxane and Hydroxychloroquine
Hide Arm/Group Description:
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 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 Number of Participants Analyzed 30 41
Measure Type: Count of Participants
Unit of Measure: Participants
Yes - robotic surgical resection procedure
8
  26.7%
10
  24.4%
No - not robotic surgical resection procedure
22
  73.3%
31
  75.6%
7.Primary Outcome
Title Age-Adjusted Charlson Comorbidity Index
Hide Description 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.
Time Frame Prior to treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Patients who went to surgery and were evaluable for Evans Grade Histopathologic Response.
Arm/Group Title Gemcitabine + Abraxane Gemcitabine + Abraxane and Hydroxychloroquine
Hide Arm/Group Description:
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 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 Number of Participants Analyzed 30 41
Measure Type: Count of Participants
Unit of Measure: Participants
Age-Adjusted CCI=2
3
  10.0%
1
   2.4%
Age-Adjusted CCI=3
5
  16.7%
2
   4.9%
Age-Adjusted CCI=4
7
  23.3%
11
  26.8%
Age-Adjusted CCI=5
8
  26.7%
15
  36.6%
Age-Adjusted CCI=6
5
  16.7%
8
  19.5%
Age-Adjusted CCI=7
2
   6.7%
2
   4.9%
Age-Adjusted CCI=8
0
   0.0%
2
   4.9%
8.Secondary Outcome
Title Carbohydrate Antigen 19-9 (CA19-9) Response
Hide Description Levels of Carbohydrate antigen 19-9 (CA19-9) response to pre-operative gemcitabine/ nab-paclitaxel measured in the serum (original scale)
Time Frame Prior to treatment (average 73.3 +/- 9.9 days prior to surgery)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants that were assigned to treatment and did not withdraw consent prior to being given drug.
Arm/Group Title Gemcitabine + Abraxane Gemcitabine + Abraxane and Hydroxychloroquine
Hide Arm/Group Description:
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 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 Number of Participants Analyzed 30 41
Mean (Standard Deviation)
Unit of Measure: units per milliliter (U/mL)
351.820  (839.925) 1534.633  (3558.1212)
9.Secondary Outcome
Title Carbohydrate Antigen 19-9 (CA19-9) Response
Hide Description Levels of Carbohydrate antigen 19-9 (CA19-9) response to pre-operative gemcitabine/ nab-paclitaxel measured in the serum (original scale).
Time Frame After treatment (50-67 days post treatment/surgery)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants that were assigned to treatment and did not withdraw consent prior to being given drug.
Arm/Group Title Gemcitabine + Abraxane Gemcitabine + Abraxane and Hydroxychloroquine
Hide Arm/Group Description:
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 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 Number of Participants Analyzed 29 41
Mean (Standard Deviation)
Unit of Measure: units per milliliter (U/mL)
319.079  (1338.259) 1696.710  (9850.273)
10.Secondary Outcome
Title Positive Lymph Node Involvement
Hide Description The proportion of participants with positive (disease) lymph nodes involvement.
Time Frame At the time of surgery (≥2 weeks and ≤6 weeks post chemotherapy)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants that were assigned to treatment and did not withdraw consent prior to being given drug.
Arm/Group Title Gemcitabine + Abraxane Gemcitabine + Abraxane and Hydroxychloroquine
Hide Arm/Group Description:
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 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 Number of Participants Analyzed 30 41
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of participants
0.8
(0.614 to 0.923)
0.561
(0.397 to 0.715)
11.Secondary Outcome
Title Rate of R0 Resection
Hide Description 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.
Time Frame At the time of surgery (≥2 weeks and ≤6 weeks post chemotherapy)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants that were assigned to treatment and did not withdraw consent prior to being given drug.
Arm/Group Title Gemcitabine + Abraxane Gemcitabine + Abraxane and Hydroxychloroquine
Hide Arm/Group Description:
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 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 Number of Participants Analyzed 30 41
Mean (95% Confidence Interval)
Unit of Measure: proportion of participants
0.7
(0.506 to 0.853)
0.829
(0.679 to 0.928)
Time Frame Up to 4 years
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Gemcitabine + Abraxane Gemcitabine + Abraxane and Hydroxychloroquine
Hide Arm/Group Description 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 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.

All-Cause Mortality
Gemcitabine + Abraxane Gemcitabine + Abraxane and Hydroxychloroquine
Affected / at Risk (%) Affected / at Risk (%)
Total   28/43 (65.12%)      34/61 (55.74%)    
Hide Serious Adverse Events
Gemcitabine + Abraxane Gemcitabine + Abraxane and Hydroxychloroquine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   30/43 (69.77%)      39/61 (63.93%)    
Blood and lymphatic system disorders     
Anemia   4/43 (9.30%)  9 3/61 (4.92%)  9
Febrile neutropenia   6/43 (13.95%)  20 2/61 (3.28%)  6
Cardiac disorders     
Atrial fibrillation   0/43 (0.00%)  0 1/61 (1.64%)  3
Ventricular fibrillation   1/43 (2.33%)  3 0/61 (0.00%)  0
Gastrointestinal disorders     
Abdominal pain   0/43 (0.00%)  0 1/61 (1.64%)  3
Diarrhea   1/43 (2.33%)  2 3/61 (4.92%)  13
Gastrointestinal disorders - Other, specify   0/43 (0.00%)  0 2/61 (3.28%)  6
Nausea   1/43 (2.33%)  2 3/61 (4.92%)  12
Vomiting   1/43 (2.33%)  2 2/61 (3.28%)  6
General disorders     
Edema limbs   0/43 (0.00%)  0 1/61 (1.64%)  3
Fatigue   2/43 (4.65%)  4 5/61 (8.20%)  18
Fever   1/43 (2.33%)  2 0/61 (0.00%)  0
Multi-organ failure   1/43 (2.33%)  3 0/61 (0.00%)  0
Pain   1/43 (2.33%)  3 0/61 (0.00%)  0
Hepatobiliary disorders     
Cholecystitis   0/43 (0.00%)  0 1/61 (1.64%)  3
Hepatobiliary disorders - Other, specify   0/43 (0.00%)  0 1/61 (1.64%)  3
Immune system disorders     
Allergic reaction   1/43 (2.33%)  2 1/61 (1.64%)  3
Infections and infestations     
Catheter related infection   1/43 (2.33%)  2 0/61 (0.00%)  0
Infections and infestations - Other, specify   3/43 (6.98%)  6 0/61 (0.00%)  0
Lung infection   2/43 (4.65%)  4 0/61 (0.00%)  0
Skin infection   3/43 (6.98%)  12 0/61 (0.00%)  0
Urinary tract infection   0/43 (0.00%)  0 1/61 (1.64%)  3
Wound infection   2/43 (4.65%)  5 0/61 (0.00%)  0
Injury, poisoning and procedural complications     
Injury, poisoning and procedural complications - Other, specify   0/43 (0.00%)  0 1/61 (1.64%)  3
Investigations     
Alanine aminotransferase increased   1/43 (2.33%)  2 6/61 (9.84%)  21
Alkaline phosphatase increased   1/43 (2.33%)  2 1/61 (1.64%)  3
Aspartate aminotransferase increased   2/43 (4.65%)  4 4/61 (6.56%)  12
Blood bilirubin increased   1/43 (2.33%)  2 1/61 (1.64%)  3
Lipase increased   0/43 (0.00%)  0 1/61 (1.64%)  3
Lymphocyte count decreased   0/43 (0.00%)  0 3/61 (4.92%)  9
Neutrophil count decreased   10/43 (23.26%)  30 11/61 (18.03%)  45
Platelet count decreased   3/43 (6.98%)  6 1/61 (1.64%)  3
White blood cell decreased   6/43 (13.95%)  12 10/61 (16.39%)  39
Metabolism and nutrition disorders     
Dehydration   1/43 (2.33%)  2 5/61 (8.20%)  21
Hyperglycemia   1/43 (2.33%)  5 0/61 (0.00%)  0
Hypoalbuminemia   0/43 (0.00%)  0 1/61 (1.64%)  3
Hyponatremia   2/43 (4.65%)  3 6/61 (9.84%)  24
Hypophosphatemia   0/43 (0.00%)  0 2/61 (3.28%)  6
Metabolism and nutrition disorders - Other, specify   1/43 (2.33%)  2 0/61 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Bone pain   0/43 (0.00%)  0 1/61 (1.64%)  3
Generalized muscle weakness   0/43 (0.00%)  0 3/61 (4.92%)  9
Pain in extremity   0/43 (0.00%)  0 1/61 (1.64%)  3
Renal and urinary disorders     
Acute kidney injury   0/43 (0.00%)  0 1/61 (1.64%)  3
Respiratory, thoracic and mediastinal disorders     
Dyspnea   0/43 (0.00%)  0 1/61 (1.64%)  3
Hypoxia   1/43 (2.33%)  2 0/61 (0.00%)  0
Pleural effusion   1/43 (2.33%)  2 0/61 (0.00%)  0
Pneumonitis   2/43 (4.65%)  5 0/61 (0.00%)  0
Vascular disorders     
Hypertension   4/43 (9.30%)  10 3/61 (4.92%)  9
Hypotension   0/43 (0.00%)  0 2/61 (3.28%)  9
Thromboembolic event   1/43 (2.33%)  3 1/61 (1.64%)  4
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Gemcitabine + Abraxane Gemcitabine + Abraxane and Hydroxychloroquine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   43/43 (100.00%)      60/61 (98.36%)    
Blood and lymphatic system disorders     
Anemia   36/43 (83.72%)  151 50/61 (81.97%)  333
Febrile neutropenia   6/43 (13.95%)  28 7/61 (11.48%)  27
Cardiac disorders     
Atrial fibrillation   0/43 (0.00%)  0 2/61 (3.28%)  6
Cardiac disorders - Other, specify   1/43 (2.33%)  2 1/61 (1.64%)  3
Chest pain - cardiac   0/43 (0.00%)  0 1/61 (1.64%)  3
Paroxysmal atrial tachycardia   1/43 (2.33%)  2 0/61 (0.00%)  0
Pulmonary valve disease   0/43 (0.00%)  0 1/61 (1.64%)  3
Sinus bradycardia   1/43 (2.33%)  4 0/61 (0.00%)  0
Sinus tachycardia   1/43 (2.33%)  2 2/61 (3.28%)  6
Supraventricular tachycardia   0/43 (0.00%)  0 1/61 (1.64%)  3
Tricuspid valve disease   0/43 (0.00%)  0 1/61 (1.64%)  3
Ventricular fibrillation   1/43 (2.33%)  3 0/61 (0.00%)  0
Ventricular tachycardia   0/43 (0.00%)  0 1/61 (1.64%)  3
Ear and labyrinth disorders     
Vertigo   0/43 (0.00%)  0 1/61 (1.64%)  3
Eye disorders     
Blurred vision   0/43 (0.00%)  0 2/61 (3.28%)  9
Eye disorders - Other, specify   1/43 (2.33%)  2 0/61 (0.00%)  0
Gastrointestinal disorders     
Abdominal pain   5/43 (11.63%)  10 8/61 (13.11%)  24
Bloating   0/43 (0.00%)  0 1/61 (1.64%)  3
Constipation   10/43 (23.26%)  26 13/61 (21.31%)  42
Diarrhea   11/43 (25.58%)  27 25/61 (40.98%)  100
Dry mouth   1/43 (2.33%)  2 0/61 (0.00%)  0
Dysphagia   0/43 (0.00%)  0 1/61 (1.64%)  3
Esophageal pain   1/43 (2.33%)  2 0/61 (0.00%)  0
Flatulence   3/43 (6.98%)  10 5/61 (8.20%)  15
Gastroesophageal reflux disease   3/43 (6.98%)  6 4/61 (6.56%)  15
Gastrointestinal disorders - Other, specify   2/43 (4.65%)  4 7/61 (11.48%)  24
Gingival pain   0/43 (0.00%)  0 1/61 (1.64%)  3
Hemorrhoids   0/43 (0.00%)  0 1/61 (1.64%)  3
Malabsorption   0/43 (0.00%)  0 1/61 (1.64%)  3
Mucositis oral   2/43 (4.65%)  4 2/61 (3.28%)  6
Nausea   12/43 (27.91%)  41 31/61 (50.82%)  126
Oral pain   0/43 (0.00%)  0 1/61 (1.64%)  3
Rectal hemorrhage   1/43 (2.33%)  2 1/61 (1.64%)  3
Toothache   0/43 (0.00%)  0 1/61 (1.64%)  3
Vomiting   6/43 (13.95%)  19 16/61 (26.23%)  48
General disorders     
Chills   2/43 (4.65%)  5 4/61 (6.56%)  13
Edema limbs   8/43 (18.60%)  18 7/61 (11.48%)  21
Edema trunk   1/43 (2.33%)  2 0/61 (0.00%)  0
Fatigue   29/43 (67.44%)  86 27/61 (44.26%)  141
Fever   6/43 (13.95%)  16 8/61 (13.11%)  28
Flu like symptoms   1/43 (2.33%)  2 4/61 (6.56%)  12
General disorders and administration site conditions - Other, specify   5/43 (11.63%)  20 7/61 (11.48%)  24
Malaise   1/43 (2.33%)  2 3/61 (4.92%)  9
Multi-organ failure   1/43 (2.33%)  3 0/61 (0.00%)  0
Pain   5/43 (11.63%)  15 4/61 (6.56%)  12
Hepatobiliary disorders     
Cholecystitis   0/43 (0.00%)  0 1/61 (1.64%)  3
Hepatobiliary disorders - Other, specify   0/43 (0.00%)  0 1/61 (1.64%)  3
Immune system disorders     
Allergic reaction   1/43 (2.33%)  4 1/61 (1.64%)  3
Infections and infestations     
Catheter related infection   1/43 (2.33%)  2 0/61 (0.00%)  0
Infections and infestations - Other, specify   3/43 (6.98%)  8 2/61 (3.28%)  6
Lung infection   2/43 (4.65%)  4 0/61 (0.00%)  0
Mucosal infection   1/43 (2.33%)  2 0/61 (0.00%)  0
Skin infection   3/43 (6.98%)  20 1/61 (1.64%)  6
Tooth infection   0/43 (0.00%)  0 1/61 (1.64%)  3
Urinary tract infection   0/43 (0.00%)  0 5/61 (8.20%)  18
Wound infection   2/43 (4.65%)  5 1/61 (1.64%)  3
Injury, poisoning and procedural complications     
Fall   0/43 (0.00%)  0 2/61 (3.28%)  6
Injury, poisoning and procedural complications - Other, specify   0/43 (0.00%)  0 1/61 (1.64%)  3
Investigations     
Activated partial thromboplastin time prolonged   1/43 (2.33%)  1 1/61 (1.64%)  3
Alanine aminotransferase increased   18/43 (41.86%)  56 32/61 (52.46%)  147
Alkaline phosphatase increased   11/43 (25.58%)  27 23/61 (37.70%)  105
Aspartate aminotransferase increased   17/43 (39.53%)  51 36/61 (59.02%)  135
Blood bilirubin increased   3/43 (6.98%)  8 7/61 (11.48%)  27
CPK increased   0/43 (0.00%)  0 1/61 (1.64%)  3
Creatinine increased   4/43 (9.30%)  8 4/61 (6.56%)  12
Hemoglobin increased   1/43 (2.33%)  2 0/61 (0.00%)  0
INR increased   1/43 (2.33%)  1 0/61 (0.00%)  0
Investigations - Other, specify   0/43 (0.00%)  0 3/61 (4.92%)  9
Lipase increased   1/43 (2.33%)  3 1/61 (1.64%)  3
Lymphocyte count decreased   13/43 (30.23%)  37 13/61 (21.31%)  63
Neutrophil count decreased   29/43 (67.44%)  123 41/61 (67.21%)  198
Platelet count decreased   30/43 (69.77%)  113 45/61 (73.77%)  228
Serum amylase increased   0/43 (0.00%)  0 1/61 (1.64%)  3
Weight loss   6/43 (13.95%)  12 5/61 (8.20%)  18
White blood cell decreased   31/43 (72.09%)  122 42/61 (68.85%)  237
Metabolism and nutrition disorders     
Anorexia   5/43 (11.63%)  10 12/61 (19.67%)  39
Dehydration   4/43 (9.30%)  9 9/61 (14.75%)  36
Hypercalcemia   1/43 (2.33%)  3 3/61 (4.92%)  9
Hyperglycemia   5/43 (11.63%)  30 3/61 (4.92%)  9
Hyperkalemia   2/43 (4.65%)  4 1/61 (1.64%)  3
Hypernatremia   2/43 (4.65%)  5 2/61 (3.28%)  6
Hypoalbuminemia   25/43 (58.14%)  92 40/61 (65.57%)  204
Hypocalcemia   1/43 (2.33%)  4 6/61 (9.84%)  30
Hypoglycemia   1/43 (2.33%)  2 1/61 (1.64%)  3
Hypokalemia   11/43 (25.58%)  33 20/61 (32.79%)  81
Hypomagnesemia   0/43 (0.00%)  0 3/61 (4.92%)  9
Hyponatremia   17/43 (39.53%)  53 28/61 (45.90%)  150
Hypophosphatemia   1/43 (2.33%)  3 4/61 (6.56%)  24
Metabolism and nutrition disorders - Other, specify   2/43 (4.65%)  10 5/61 (8.20%)  18
Musculoskeletal and connective tissue disorders     
Arthralgia   1/43 (2.33%)  2 1/61 (1.64%)  3
Back pain   3/43 (6.98%)  6 3/61 (4.92%)  9
Bone pain   0/43 (0.00%)  0 1/61 (1.64%)  3
Generalized muscle weakness   0/43 (0.00%)  0 10/61 (16.39%)  57
Muscle weakness lower limb   1/43 (2.33%)  2 1/61 (1.64%)  3
Musculoskeletal and connective tissue disorder - Other, specify   2/43 (4.65%)  4 2/61 (3.28%)  12
Myalgia   2/43 (4.65%)  4 1/61 (1.64%)  3
Pain in extremity   0/43 (0.00%)  0 3/61 (4.92%)  12
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify   0/43 (0.00%)  0 1/61 (1.64%)  3
Nervous system disorders     
Dizziness   1/43 (2.33%)  3 3/61 (4.92%)  9
Dysgeusia   1/43 (2.33%)  2 2/61 (3.28%)  9
Headache   1/43 (2.33%)  2 3/61 (4.92%)  9
Memory impairment   1/43 (2.33%)  2 0/61 (0.00%)  0
Nervous system disorders - Other, specify   1/43 (2.33%)  2 3/61 (4.92%)  12
Paresthesia   0/43 (0.00%)  0 1/61 (1.64%)  6
Peripheral motor neuropathy   1/43 (2.33%)  2 0/61 (0.00%)  0
Peripheral sensory neuropathy   2/43 (4.65%)  6 6/61 (9.84%)  24
Somnolence   0/43 (0.00%)  0 1/61 (1.64%)  4
Tremor   0/43 (0.00%)  0 1/61 (1.64%)  3
Psychiatric disorders     
Anxiety   4/43 (9.30%)  8 3/61 (4.92%)  9
Confusion   1/43 (2.33%)  2 1/61 (1.64%)  3
Depression   1/43 (2.33%)  2 2/61 (3.28%)  6
Insomnia   1/43 (2.33%)  2 5/61 (8.20%)  15
Renal and urinary disorders     
Acute kidney injury   0/43 (0.00%)  0 2/61 (3.28%)  6
Hematuria   0/43 (0.00%)  0 1/61 (1.64%)  3
Renal and urinary disorders - Other, specify   1/43 (2.33%)  2 0/61 (0.00%)  0
Urinary retention   0/43 (0.00%)  0 2/61 (3.28%)  6
Urinary tract obstruction   0/43 (0.00%)  0 1/61 (1.64%)  3
Reproductive system and breast disorders     
Reproductive system and breast disorders - Other, specify   0/43 (0.00%)  0 1/61 (1.64%)  3
Respiratory, thoracic and mediastinal disorders     
Allergic rhinitis   1/43 (2.33%)  2 1/61 (1.64%)  3
Cough   3/43 (6.98%)  6 2/61 (3.28%)  6
Dyspnea   1/43 (2.33%)  2 5/61 (8.20%)  18
Epistaxis   2/43 (4.65%)  5 1/61 (1.64%)  3
Hiccups   0/43 (0.00%)  0 1/61 (1.64%)  3
Hypoxia   2/43 (4.65%)  4 0/61 (0.00%)  0
Nasal congestion   1/43 (2.33%)  2 1/61 (1.64%)  3
Pleural effusion   1/43 (2.33%)  2 0/61 (0.00%)  0
Pneumonitis   2/43 (4.65%)  5 0/61 (0.00%)  0
Respiratory, thoracic and mediastinal disorders - Other, specify   3/43 (6.98%)  6 6/61 (9.84%)  18
Sore throat   0/43 (0.00%)  0 1/61 (1.64%)  3
Wheezing   1/43 (2.33%)  2 0/61 (0.00%)  0
Skin and subcutaneous tissue disorders     
Alopecia   3/43 (6.98%)  6 10/61 (16.39%)  39
Dry skin   0/43 (0.00%)  0 3/61 (4.92%)  9
Erythema multiforme   0/43 (0.00%)  0 1/61 (1.64%)  3
Nail discoloration   1/43 (2.33%)  2 0/61 (0.00%)  0
Pruritus   1/43 (2.33%)  2 2/61 (3.28%)  6
Rash acneiform   0/43 (0.00%)  0 3/61 (4.92%)  9
Rash maculo-papular   0/43 (0.00%)  0 4/61 (6.56%)  12
Skin and subcutaneous tissue disorders - Other, specify   2/43 (4.65%)  5 8/61 (13.11%)  33
Skin hyperpigmentation   0/43 (0.00%)  0 1/61 (1.64%)  3
Vascular disorders     
Flushing   0/43 (0.00%)  0 1/61 (1.64%)  3
Hematoma   1/43 (2.33%)  2 0/61 (0.00%)  0
Hot flashes   0/43 (0.00%)  0 1/61 (1.64%)  3
Hypertension   13/43 (30.23%)  59 14/61 (22.95%)  60
Hypotension   1/43 (2.33%)  2 9/61 (14.75%)  33
Phlebitis   0/43 (0.00%)  0 1/61 (1.64%)  3
Superficial thrombophlebitis   0/43 (0.00%)  0 1/61 (1.64%)  3
Thromboembolic event   1/43 (2.33%)  5 2/61 (3.28%)  7
Vascular disorders - Other, specify   1/43 (2.33%)  2 0/61 (0.00%)  0
Indicates events were collected by systematic assessment
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: Barbara Stadterman
Organization: UPMC Hillman Cancer Center
Phone: 412-647-5554
EMail: stadtermanbm@upmc.edu
Layout table for additonal information
Responsible Party: Nathan Bahary, MD, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT01978184    
Other Study ID Numbers: UPCI# 13-074
First Submitted: October 30, 2013
First Posted: November 7, 2013
Results First Submitted: March 3, 2019
Results First Posted: March 27, 2019
Last Update Posted: March 27, 2019