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Gemcitabine Hydrochloride With or Without Vismodegib in Treating Patients With Recurrent or Metastatic Pancreatic Cancer

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ClinicalTrials.gov Identifier: NCT01064622
Recruitment Status : Completed
First Posted : February 8, 2010
Results First Posted : February 13, 2015
Last Update Posted : August 14, 2015
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Adenocarcinoma of the Pancreas
Recurrent Pancreatic Cancer
Stage IV Pancreatic Cancer
Interventions Drug: vismodegib
Drug: gemcitabine hydrochloride
Other: hydrocortisone/placebo
Enrollment 118
Recruitment Details  
Pre-assignment Details Prior to the phase II randomized trial, an open-label, lead-in phase I study was conducted with all patients receiving gemcitabine hydrochloride plus vismodegib. Seven patients were enrolled and no safety issues were identified.
Arm/Group Title Arm I (Gemcitabine Hydrochloride and Placebo) Arm II (Gemcitabine Hydrochloride and Vismodegib)
Hide Arm/Group Description

Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 and placebo PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. At the time of disease progression, patients are unblinded and may crossover to arm II.

gemcitabine hydrochloride: Given IV

hydrocortisone/placebo: Given PO

Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 and vismodegib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

vismodegib: Given PO

gemcitabine hydrochloride: Given IV

Period Title: Lead-in Phase I
Started 0 7
Completed 0 7
Not Completed 0 0
Period Title: Randomized Phase II
Started 55 56
Completed 53 53
Not Completed 2 3
Reason Not Completed
Withdrawal by Subject             2             2
Protocol Violation             0             1
Period Title: Crossover of Arm I
Started 22 [1] 0
Completed 22 0
Not Completed 0 0
[1]
Among 53 patients, 45 had disease progression; however 23 elected not to crossover to vismodegib.
Arm/Group Title Arm I (Gemcitabine Hydrochloride and Placebo) Arm II (Gemcitabine Hydrochloride and Vismodegib) Phase I lead-in Patients Total
Hide Arm/Group Description

Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 and placebo PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. At the time of disease progression, patients are unblinded and may crossover to arm II.

gemcitabine hydrochloride: Given IV

hydrocortisone/placebo: Given PO

Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 and vismodegib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

vismodegib: Given PO

gemcitabine hydrochloride: Given IV

Patients enrolled in the lead-in phase I portion of the trial. Patients receive 1000 mg/m2 gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 and 150 mg vismodegib PO QD on days 1-28. Total of all reporting groups
Overall Number of Baseline Participants 53 53 7 113
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous   [1] 
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 53 participants 53 participants 7 participants 113 participants
64.5
(39 to 84)
64.7
(49 to 82)
56.7
(43 to 72)
64.1
(39 to 84)
[1]
Measure Description: One age value missing from Arm I.
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 53 participants 53 participants 7 participants 113 participants
Female
26
  49.1%
22
  41.5%
2
  28.6%
50
  44.2%
Male
27
  50.9%
31
  58.5%
5
  71.4%
63
  55.8%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 53 participants 53 participants 7 participants 113 participants
American Indian or Alaska Native
0
   0.0%
1
   1.9%
0
   0.0%
1
   0.9%
Asian
0
   0.0%
1
   1.9%
0
   0.0%
1
   0.9%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
6
  11.3%
10
  18.9%
0
   0.0%
16
  14.2%
White
45
  84.9%
40
  75.5%
7
 100.0%
92
  81.4%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
2
   3.8%
1
   1.9%
0
   0.0%
3
   2.7%
1.Primary Outcome
Title Progression-free Survival
Hide Description Time from randomization to disease progression or death from any cause. Estimated in the two treatment groups by the Kaplan-Meier method and compared using a stratified logrank test.
Time Frame Up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
Phase I lead-in patients were not included in the efficacy analysis.
Arm/Group Title Arm I (Gemcitabine Hydrochloride and Placebo) Arm II (Gemcitabine Hydrochloride and Vismodegib) Phase I lead-in Patients
Hide Arm/Group Description:

Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 and placebo PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. At the time of disease progression, patients are unblinded and may crossover to arm II.

gemcitabine hydrochloride: Given IV

hydrocortisone/placebo: Given PO

Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 and vismodegib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

vismodegib: Given PO

gemcitabine hydrochloride: Given IV

Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 and vismodegib PO QD on days 1-28.
Overall Number of Participants Analyzed 53 53 0
Median (95% Confidence Interval)
Unit of Measure: months
2.5
(1.9 to 3.8)
4.0
(2.5 to 5.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm I (Gemcitabine Hydrochloride and Placebo), Arm II (Gemcitabine Hydrochloride and Vismodegib)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.15
Comments Reported p-value is one-sided. p<0.10 required for statistical significance.
Method Log Rank
Comments Stratified by Karnofsky performance status (90-100 vs. 80) and disease status (newly diagnosed vs. recurrent after surgery)
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.82
Confidence Interval (2-Sided) 95%
0.55 to 1.22
Estimation Comments Hazard ratio is for (gemcitabine hydrochloride plus vismodegib)/(gemcitabine hydrochloride plus placebo), adjusted for Karnofsky performance status (90-100 vs. 80) and disease status (newly diagnosed vs. recurrent after surgery)
2.Secondary Outcome
Title Overall Survival
Hide Description Time from randomization to death from any cause. Estimated in the two treatment groups by the Kaplan-Meier method and compared using a stratified logrank test.
Time Frame Up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
Phase I lead-in patients were not included in the efficacy analysis.
Arm/Group Title Arm I (Gemcitabine Hydrochloride and Placebo) Arm II (Gemcitabine Hydrochloride and Vismodegib) Phase I lead-in Patients
Hide Arm/Group Description:

Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 and placebo PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. At the time of disease progression, patients are unblinded and may crossover to arm II.

gemcitabine hydrochloride: Given IV

hydrocortisone/placebo: Given PO

Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 and vismodegib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

vismodegib: Given PO

gemcitabine hydrochloride: Given IV

Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 and vismodegib PO QD on days 1-28.
Overall Number of Participants Analyzed 53 53 0
Median (95% Confidence Interval)
Unit of Measure: months
6.1
(5.0 to 8.1)
6.9
(5.8 to 8.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm I (Gemcitabine Hydrochloride and Placebo), Arm II (Gemcitabine Hydrochloride and Vismodegib)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.37
Comments [Not Specified]
Method Log Rank
Comments Stratified by Karnofsky performance status (90-100 vs. 80) and disease status (newly diagnosed vs. recurrent after surgery)
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.96
Confidence Interval (2-Sided) 95%
0.64 to 1.46
Estimation Comments Hazard ratio is for (gemcitabine hydrochloride plus vismodegib)/(gemcitabine hydrochloride plus placebo), adjusted for Karnofsky performance status (90-100 vs. 80) and disease status (newly diagnosed vs. recurrent after surgery)
3.Secondary Outcome
Title Objective Response Rate
Hide Description Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time Frame Up to 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Phase I lead-in patients were not included in the efficacy analysis.
Arm/Group Title Arm I (Gemcitabine Hydrochloride and Placebo) Arm II (Gemcitabine Hydrochloride and Vismodegib) Phase I lead-in Patients
Hide Arm/Group Description:

Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 and placebo PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. At the time of disease progression, patients are unblinded and may crossover to arm II.

gemcitabine hydrochloride: Given IV

hydrocortisone/placebo: Given PO

Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 and vismodegib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

vismodegib: Given PO

gemcitabine hydrochloride: Given IV

Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 and vismodegib PO QD on days 1-28.
Overall Number of Participants Analyzed 53 53 0
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
13.2
(5.5 to 25.3)
7.5
(2.1 to 18.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm I (Gemcitabine Hydrochloride and Placebo), Arm II (Gemcitabine Hydrochloride and Vismodegib)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.42
Comments Two-sided p-value for Cochran-Mantel-Haenszel test stratified by Karnofsky performance status and disease status.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
4.Secondary Outcome
Title Incidence of Adverse Events
Hide Description Details are provided in Adverse Events section below. Reported here are percentage of patients in each arm with any grade 1 or higher adverse event, regardless of attribution.
Time Frame Up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm I (Gemcitabine Hydrochloride and Placebo) Arm II (Gemcitabine Hydrochloride and Vismodegib) Phase I lead-in Patients
Hide Arm/Group Description:

Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 and placebo PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. At the time of disease progression, patients are unblinded and may crossover to arm II.

gemcitabine hydrochloride: Given IV

hydrocortisone/placebo: Given PO

Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 and vismodegib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

vismodegib: Given PO

gemcitabine hydrochloride: Given IV

Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 and vismodegib PO QD on days 1-28.
Overall Number of Participants Analyzed 53 53 7
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
98.1
(89.9 to 99.9)
98.1
(89.9 to 99.9)
100.0
(59.0 to 100.0)
5.Secondary Outcome
Title Activity (Overall Response Rate) in Crossover Patients
Hide Description RECIST response rate in patients after crossover from placebo to vismodegib arm. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time Frame Up to 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Phase I lead-in patients were not included in the efficacy analyses.
Arm/Group Title Arm I (Gemcitabine Hydrochloride and Placebo) Arm II (Gemcitabine Hydrochloride and Vismodegib) Phase I lead-in Patients
Hide Arm/Group Description:

Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 and placebo PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. At the time of disease progression, patients are unblinded and may crossover to arm II.

gemcitabine hydrochloride: Given IV

hydrocortisone/placebo: Given PO

Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 and vismodegib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

vismodegib: Given PO

gemcitabine hydrochloride: Given IV

Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 and vismodegib PO QD on days 1-28.
Overall Number of Participants Analyzed 22 0 0
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
4.5
(0.1 to 22.8)
Time Frame Up to 3 years.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Arm I (Gemcitabine Hydrochloride and Placebo) Arm II (Gemcitabine Hydrochloride and Vismodegib) Phase I lead-in Patients Phase II Crossover Patients
Hide Arm/Group Description

Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 and placebo PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. At the time of disease progression, patients are unblinded and may crossover to arm II.

gemcitabine hydrochloride: Given IV

hydrocortisone/placebo: Given PO

Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 and vismodegib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

vismodegib: Given PO

gemcitabine hydrochloride: Given IV

Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 and vismodegib PO QD on days 1-28. Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 and vismodegib PO QD on days 1-28.
All-Cause Mortality
Arm I (Gemcitabine Hydrochloride and Placebo) Arm II (Gemcitabine Hydrochloride and Vismodegib) Phase I lead-in Patients Phase II Crossover Patients
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Arm I (Gemcitabine Hydrochloride and Placebo) Arm II (Gemcitabine Hydrochloride and Vismodegib) Phase I lead-in Patients Phase II Crossover Patients
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   37/53 (69.81%)   22/53 (41.51%)   5/7 (71.43%)   4/22 (18.18%) 
Blood and lymphatic system disorders         
Anemia *  0/53 (0.00%)  4/53 (7.55%)  0/7 (0.00%)  0/22 (0.00%) 
Febrile neutropenia *  1/53 (1.89%)  1/53 (1.89%)  0/7 (0.00%)  0/22 (0.00%) 
Leukocytosis *  0/53 (0.00%)  1/53 (1.89%)  0/7 (0.00%)  0/22 (0.00%) 
Thrombotic thrombocytopenic purpura *  0/53 (0.00%)  1/53 (1.89%)  0/7 (0.00%)  0/22 (0.00%) 
Cardiac disorders         
Atrial fibrillation *  0/53 (0.00%)  1/53 (1.89%)  0/7 (0.00%)  0/22 (0.00%) 
Cardiac arrest *  1/53 (1.89%)  0/53 (0.00%)  0/7 (0.00%)  0/22 (0.00%) 
Gastrointestinal disorders         
Metastatic Pancreatic Cancer *  0/53 (0.00%)  1/53 (1.89%)  0/7 (0.00%)  0/22 (0.00%) 
disease progression *  1/53 (1.89%)  0/53 (0.00%)  0/7 (0.00%)  0/22 (0.00%) 
neoplasmsbenign, malignant and unspecified *  1/53 (1.89%)  0/53 (0.00%)  0/7 (0.00%)  0/22 (0.00%) 
progression of disease *  1/53 (1.89%)  0/53 (0.00%)  0/7 (0.00%)  0/22 (0.00%) 
progression of metastatic pancreatic cancer *  1/53 (1.89%)  0/53 (0.00%)  0/7 (0.00%)  0/22 (0.00%) 
progressive disease *  0/53 (0.00%)  2/53 (3.77%)  0/7 (0.00%)  0/22 (0.00%) 
Abdominal distension *  1/53 (1.89%)  0/53 (0.00%)  0/7 (0.00%)  0/22 (0.00%) 
Abdominal pain *  2/53 (3.77%)  3/53 (5.66%)  1/7 (14.29%)  0/22 (0.00%) 
Ascites *  1/53 (1.89%)  1/53 (1.89%)  1/7 (14.29%)  0/22 (0.00%) 
Constipation *  1/53 (1.89%)  2/53 (3.77%)  1/7 (14.29%)  0/22 (0.00%) 
Diarrhea *  0/53 (0.00%)  1/53 (1.89%)  0/7 (0.00%)  0/22 (0.00%) 
Duodenal obstruction *  1/53 (1.89%)  0/53 (0.00%)  0/7 (0.00%)  0/22 (0.00%) 
Ileus *  1/53 (1.89%)  0/53 (0.00%)  0/7 (0.00%)  0/22 (0.00%) 
Jejunal obstruction *  0/53 (0.00%)  1/53 (1.89%)  0/7 (0.00%)  0/22 (0.00%) 
Nausea *  6/53 (11.32%)  4/53 (7.55%)  0/7 (0.00%)  0/22 (0.00%) 
Obstruction gastric *  0/53 (0.00%)  1/53 (1.89%)  0/7 (0.00%)  0/22 (0.00%) 
Small intestinal obstruction *  1/53 (1.89%)  0/53 (0.00%)  0/7 (0.00%)  0/22 (0.00%) 
Small intestinal perforation *  1/53 (1.89%)  0/53 (0.00%)  0/7 (0.00%)  0/22 (0.00%) 
Upper gastrointestinal hemorrhage *  1/53 (1.89%)  0/53 (0.00%)  0/7 (0.00%)  0/22 (0.00%) 
Vomiting *  6/53 (11.32%)  3/53 (5.66%)  2/7 (28.57%)  0/22 (0.00%) 
Pancreatitis *  0/53 (0.00%)  0/53 (0.00%)  1/7 (14.29%)  0/22 (0.00%) 
General disorders         
Death *  1/53 (1.89%)  0/53 (0.00%)  0/7 (0.00%)  0/22 (0.00%) 
Death due to disease progression *  1/53 (1.89%)  0/53 (0.00%)  0/7 (0.00%)  0/22 (0.00%) 
failure to thrive *  0/53 (0.00%)  1/53 (1.89%)  0/7 (0.00%)  1/22 (4.55%) 
Death NOS *  6/53 (11.32%)  4/53 (7.55%)  1/7 (14.29%)  0/22 (0.00%) 
Fatigue *  2/53 (3.77%)  2/53 (3.77%)  0/7 (0.00%)  0/22 (0.00%) 
Fever *  4/53 (7.55%)  1/53 (1.89%)  0/7 (0.00%)  0/22 (0.00%) 
Pain *  1/53 (1.89%)  0/53 (0.00%)  0/7 (0.00%)  0/22 (0.00%) 
Hepatobiliary disorders         
Cholangitis *  1/53 (1.89%)  0/53 (0.00%)  0/7 (0.00%)  0/22 (0.00%) 
cholestasis *  0/53 (0.00%)  1/53 (1.89%)  0/7 (0.00%)  0/22 (0.00%) 
Bile duct stenosis *  1/53 (1.89%)  0/53 (0.00%)  0/7 (0.00%)  0/22 (0.00%) 
Infections and infestations         
Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L): Urinary tract NOS *  1/53 (1.89%)  0/53 (0.00%)  0/7 (0.00%)  0/22 (0.00%) 
Infection with normal ANC or Grade 1 or 2 neutrophils: Blood *  0/53 (0.00%)  1/53 (1.89%)  0/7 (0.00%)  0/22 (0.00%) 
Abdominal infection *  1/53 (1.89%)  0/53 (0.00%)  0/7 (0.00%)  0/22 (0.00%) 
Biliary tract infection *  0/53 (0.00%)  1/53 (1.89%)  0/7 (0.00%)  0/22 (0.00%) 
Catheter related infection *  0/53 (0.00%)  1/53 (1.89%)  0/7 (0.00%)  0/22 (0.00%) 
Device related infection *  1/53 (1.89%)  0/53 (0.00%)  0/7 (0.00%)  0/22 (0.00%) 
Hepatic infection *  0/53 (0.00%)  1/53 (1.89%)  0/7 (0.00%)  0/22 (0.00%) 
Lung infection *  1/53 (1.89%)  2/53 (3.77%)  0/7 (0.00%)  1/22 (4.55%) 
Peritoneal infection *  2/53 (3.77%)  0/53 (0.00%)  0/7 (0.00%)  0/22 (0.00%) 
Sepsis *  0/53 (0.00%)  1/53 (1.89%)  0/7 (0.00%)  0/22 (0.00%) 
Skin infection *  1/53 (1.89%)  0/53 (0.00%)  0/7 (0.00%)  0/22 (0.00%) 
Urinary tract infection *  0/53 (0.00%)  1/53 (1.89%)  0/7 (0.00%)  0/22 (0.00%) 
Infection * [1]  0/53 (0.00%)  0/53 (0.00%)  0/7 (0.00%)  1/22 (4.55%) 
Injury, poisoning and procedural complications         
Vascular access complication *  1/53 (1.89%)  0/53 (0.00%)  0/7 (0.00%)  0/22 (0.00%) 
Investigations         
Alanine aminotransferase increased *  3/53 (5.66%)  1/53 (1.89%)  0/7 (0.00%)  0/22 (0.00%) 
Alkaline phosphatase increased *  0/53 (0.00%)  2/53 (3.77%)  0/7 (0.00%)  0/22 (0.00%) 
Aspartate aminotransferase increased *  3/53 (5.66%)  2/53 (3.77%)  0/7 (0.00%)  0/22 (0.00%) 
Blood bilirubin increased *  0/53 (0.00%)  6/53 (11.32%)  0/7 (0.00%)  0/22 (0.00%) 
Cardiac troponin I increased *  1/53 (1.89%)  0/53 (0.00%)  0/7 (0.00%)  0/22 (0.00%) 
Creatinine increased *  1/53 (1.89%)  1/53 (1.89%)  0/7 (0.00%)  0/22 (0.00%) 
INR increased *  1/53 (1.89%)  0/53 (0.00%)  0/7 (0.00%)  0/22 (0.00%) 
Lymphocyte count decreased *  1/53 (1.89%)  0/53 (0.00%)  0/7 (0.00%)  0/22 (0.00%) 
Neutrophil count decreased *  2/53 (3.77%)  3/53 (5.66%)  0/7 (0.00%)  0/22 (0.00%) 
Platelet count decreased *  2/53 (3.77%)  3/53 (5.66%)  1/7 (14.29%)  0/22 (0.00%) 
Weight loss *  1/53 (1.89%)  0/53 (0.00%)  0/7 (0.00%)  0/22 (0.00%) 
White blood cell decreased *  1/53 (1.89%)  1/53 (1.89%)  0/7 (0.00%)  0/22 (0.00%) 
Metabolism and nutrition disorders         
Anorexia *  0/53 (0.00%)  2/53 (3.77%)  0/7 (0.00%)  0/22 (0.00%) 
Dehydration *  1/53 (1.89%)  1/53 (1.89%)  1/7 (14.29%)  0/22 (0.00%) 
Hyperglycemia *  2/53 (3.77%)  1/53 (1.89%)  0/7 (0.00%)  1/22 (4.55%) 
Hypoglycemia *  0/53 (0.00%)  1/53 (1.89%)  0/7 (0.00%)  0/22 (0.00%) 
Hypokalemia *  0/53 (0.00%)  1/53 (1.89%)  0/7 (0.00%)  0/22 (0.00%) 
Hypoalbuminemia *  0/53 (0.00%)  0/53 (0.00%)  1/7 (14.29%)  0/22 (0.00%) 
Musculoskeletal and connective tissue disorders         
Generalized muscle weakness *  0/53 (0.00%)  1/53 (1.89%)  0/7 (0.00%)  0/22 (0.00%) 
Nervous system disorders         
Dizziness *  1/53 (1.89%)  1/53 (1.89%)  0/7 (0.00%)  0/22 (0.00%) 
Ischemia cerebrovascular *  0/53 (0.00%)  1/53 (1.89%)  0/7 (0.00%)  0/22 (0.00%) 
Nervous system disorders - Other *  1/53 (1.89%)  1/53 (1.89%)  0/7 (0.00%)  0/22 (0.00%) 
Stroke *  1/53 (1.89%)  0/53 (0.00%)  0/7 (0.00%)  0/22 (0.00%) 
Syncope *  1/53 (1.89%)  0/53 (0.00%)  0/7 (0.00%)  0/22 (0.00%) 
Tremor *  0/53 (0.00%)  1/53 (1.89%)  0/7 (0.00%)  0/22 (0.00%) 
Psychiatric disorders         
Confusion *  0/53 (0.00%)  1/53 (1.89%)  0/7 (0.00%)  0/22 (0.00%) 
Hallucinations *  1/53 (1.89%)  0/53 (0.00%)  0/7 (0.00%)  0/22 (0.00%) 
Renal and urinary disorders         
Acute kidney injury *  1/53 (1.89%)  2/53 (3.77%)  0/7 (0.00%)  0/22 (0.00%) 
Renal and urinary disorders - Other *  0/53 (0.00%)  1/53 (1.89%)  0/7 (0.00%)  0/22 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Dyspnea *  0/53 (0.00%)  2/53 (3.77%)  0/7 (0.00%)  0/22 (0.00%) 
Pleural effusion *  1/53 (1.89%)  0/53 (0.00%)  0/7 (0.00%)  0/22 (0.00%) 
Pneumonitis *  1/53 (1.89%)  0/53 (0.00%)  0/7 (0.00%)  0/22 (0.00%) 
Pulmonary edema *  2/53 (3.77%)  0/53 (0.00%)  0/7 (0.00%)  0/22 (0.00%) 
Respiratory failure *  1/53 (1.89%)  0/53 (0.00%)  0/7 (0.00%)  0/22 (0.00%) 
Skin and subcutaneous tissue disorders         
Alopecia *  1/53 (1.89%)  0/53 (0.00%)  0/7 (0.00%)  0/22 (0.00%) 
Vascular disorders         
Hypertension *  1/53 (1.89%)  0/53 (0.00%)  0/7 (0.00%)  0/22 (0.00%) 
Peripheral ischemia *  0/53 (0.00%)  1/53 (1.89%)  0/7 (0.00%)  0/22 (0.00%) 
Thromboembolic event *  4/53 (7.55%)  2/53 (3.77%)  1/7 (14.29%)  0/22 (0.00%) 
*
Indicates events were collected by non-systematic assessment
[1]
NOS
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Arm I (Gemcitabine Hydrochloride and Placebo) Arm II (Gemcitabine Hydrochloride and Vismodegib) Phase I lead-in Patients Phase II Crossover Patients
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   52/53 (98.11%)   52/53 (98.11%)   7/7 (100.00%)   22/22 (100.00%) 
Blood and lymphatic system disorders         
Anemia *  41/53 (77.36%)  40/53 (75.47%)  6/7 (85.71%)  17/22 (77.27%) 
Cardiac disorders         
Pericardial effusion *  0/53 (0.00%)  0/53 (0.00%)  1/7 (14.29%)  0/22 (0.00%) 
Gastrointestinal disorders         
Abdominal pain *  19/53 (35.85%)  10/53 (18.87%)  3/7 (42.86%)  6/22 (27.27%) 
Ascites *  1/53 (1.89%)  4/53 (7.55%)  1/7 (14.29%)  0/22 (0.00%) 
Constipation *  14/53 (26.42%)  17/53 (32.08%)  5/7 (71.43%)  8/22 (36.36%) 
Diarrhea *  12/53 (22.64%)  13/53 (24.53%)  0/7 (0.00%)  3/22 (13.64%) 
Dry mouth *  4/53 (7.55%)  3/53 (5.66%)  0/7 (0.00%)  0/22 (0.00%) 
Dyspepsia *  5/53 (9.43%)  4/53 (7.55%)  0/7 (0.00%)  0/22 (0.00%) 
Flatulence *  5/53 (9.43%)  5/53 (9.43%)  0/7 (0.00%)  0/22 (0.00%) 
Gastrointestinal disorders - Other *  5/53 (9.43%)  6/53 (11.32%)  0/7 (0.00%)  0/22 (0.00%) 
Mucositis oral *  3/53 (5.66%)  3/53 (5.66%)  0/7 (0.00%)  0/22 (0.00%) 
Nausea *  29/53 (54.72%)  29/53 (54.72%)  5/7 (71.43%)  9/22 (40.91%) 
Vomiting *  18/53 (33.96%)  19/53 (35.85%)  5/7 (71.43%)  5/22 (22.73%) 
Dysphagia, esophagiti9s, odynophagia *  0/53 (0.00%)  0/53 (0.00%)  1/7 (14.29%)  0/22 (0.00%) 
Pancreatitis *  0/53 (0.00%)  0/53 (0.00%)  1/7 (14.29%)  0/22 (0.00%) 
General disorders         
Chills *  8/53 (15.09%)  6/53 (11.32%)  0/7 (0.00%)  0/22 (0.00%) 
Edema limbs *  13/53 (24.53%)  9/53 (16.98%)  1/7 (14.29%)  0/22 (0.00%) 
Fatigue *  36/53 (67.92%)  37/53 (69.81%)  5/7 (71.43%)  12/22 (54.55%) 
Fever *  7/53 (13.21%)  12/53 (22.64%)  1/7 (14.29%)  4/22 (18.18%) 
General disorders and administration site conditions - Other *  5/53 (9.43%)  7/53 (13.21%)  0/7 (0.00%)  0/22 (0.00%) 
Pain *  6/53 (11.32%)  14/53 (26.42%)  2/7 (28.57%)  7/22 (31.82%) 
Cancer pain *  0/53 (0.00%)  0/53 (0.00%)  1/7 (14.29%)  0/22 (0.00%) 
Death NOS *  0/53 (0.00%)  0/53 (0.00%)  7/7 (100.00%)  0/22 (0.00%) 
Infections and infestations         
Infections and infestations - Other *  0/53 (0.00%)  4/53 (7.55%)  0/7 (0.00%)  0/22 (0.00%) 
Injury, poisoning and procedural complications         
Vascular access complication *  0/53 (0.00%)  0/53 (0.00%)  1/7 (14.29%)  0/22 (0.00%) 
Investigations         
Alanine aminotransferase increased *  27/53 (50.94%)  28/53 (52.83%)  6/7 (85.71%)  9/22 (40.91%) 
Alkaline phosphatase increased *  23/53 (43.40%)  25/53 (47.17%)  6/7 (85.71%)  11/22 (50.00%) 
Aspartate aminotransferase increased *  29/53 (54.72%)  25/53 (47.17%)  4/7 (57.14%)  13/22 (59.09%) 
Blood bilirubin increased *  12/53 (22.64%)  11/53 (20.75%)  2/7 (28.57%)  6/22 (27.27%) 
Creatinine increased *  6/53 (11.32%)  5/53 (9.43%)  1/7 (14.29%)  3/22 (13.64%) 
Investigations - Other *  3/53 (5.66%)  5/53 (9.43%)  0/7 (0.00%)  0/22 (0.00%) 
Lymphocyte count decreased *  17/53 (32.08%)  9/53 (16.98%)  0/7 (0.00%)  7/22 (31.82%) 
Neutrophil count decreased *  25/53 (47.17%)  28/53 (52.83%)  3/7 (42.86%)  6/22 (27.27%) 
Platelet count decreased *  30/53 (56.60%)  32/53 (60.38%)  6/7 (85.71%)  8/22 (36.36%) 
Weight loss *  10/53 (18.87%)  11/53 (20.75%)  0/7 (0.00%)  0/22 (0.00%) 
White blood cell decreased *  31/53 (58.49%)  27/53 (50.94%)  5/7 (71.43%)  9/22 (40.91%) 
Activated partial thromboplastin time prolonged *  0/53 (0.00%)  0/53 (0.00%)  1/7 (14.29%)  0/22 (0.00%) 
Metabolism and nutrition disorders         
Anorexia *  18/53 (33.96%)  20/53 (37.74%)  5/7 (71.43%)  9/22 (40.91%) 
Dehydration *  10/53 (18.87%)  6/53 (11.32%)  0/7 (0.00%)  2/22 (9.09%) 
Hypercalcemia *  2/53 (3.77%)  3/53 (5.66%)  0/7 (0.00%)  0/22 (0.00%) 
Hyperglycemia *  26/53 (49.06%)  28/53 (52.83%)  4/7 (57.14%)  11/22 (50.00%) 
Hyperkalemia *  5/53 (9.43%)  7/53 (13.21%)  0/7 (0.00%)  0/22 (0.00%) 
Hypermagnesemia *  3/53 (5.66%)  1/53 (1.89%)  0/7 (0.00%)  0/22 (0.00%) 
Hypoalbuminemia *  30/53 (56.60%)  24/53 (45.28%)  2/7 (28.57%)  14/22 (63.64%) 
Hypocalcemia *  21/53 (39.62%)  17/53 (32.08%)  3/7 (42.86%)  7/22 (31.82%) 
Hypoglycemia *  3/53 (5.66%)  5/53 (9.43%)  1/7 (14.29%)  0/22 (0.00%) 
Hypokalemia *  12/53 (22.64%)  17/53 (32.08%)  2/7 (28.57%)  4/22 (18.18%) 
Hypomagnesemia *  12/53 (22.64%)  13/53 (24.53%)  2/7 (28.57%)  2/22 (9.09%) 
Hyponatremia *  21/53 (39.62%)  16/53 (30.19%)  4/7 (57.14%)  10/22 (45.45%) 
Hypophosphatemia *  6/53 (11.32%)  7/53 (13.21%)  0/7 (0.00%)  0/22 (0.00%) 
Musculoskeletal and connective tissue disorders         
Arthralgia *  0/53 (0.00%)  4/53 (7.55%)  0/7 (0.00%)  0/22 (0.00%) 
Back pain *  10/53 (18.87%)  9/53 (16.98%)  1/7 (14.29%)  3/22 (13.64%) 
Generalized muscle weakness *  2/53 (3.77%)  3/53 (5.66%)  2/7 (28.57%)  0/22 (0.00%) 
Musculoskeletal and connective tissue disorder - Other *  0/53 (0.00%)  5/53 (9.43%)  0/7 (0.00%)  2/22 (9.09%) 
Neck pain *  1/53 (1.89%)  3/53 (5.66%)  0/7 (0.00%)  0/22 (0.00%) 
Pain in extremity *  6/53 (11.32%)  10/53 (18.87%)  1/7 (14.29%)  4/22 (18.18%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other *  6/53 (11.32%)  2/53 (3.77%)  0/7 (0.00%)  0/22 (0.00%) 
Nervous system disorders         
Dizziness *  4/53 (7.55%)  6/53 (11.32%)  0/7 (0.00%)  2/22 (9.09%) 
Dysgeusia *  4/53 (7.55%)  12/53 (22.64%)  1/7 (14.29%)  2/22 (9.09%) 
Headache *  7/53 (13.21%)  10/53 (18.87%)  0/7 (0.00%)  0/22 (0.00%) 
Peripheral sensory neuropathy *  5/53 (9.43%)  7/53 (13.21%)  0/7 (0.00%)  3/22 (13.64%) 
Syncope *  3/53 (5.66%)  0/53 (0.00%)  0/7 (0.00%)  0/22 (0.00%) 
Psychiatric disorders         
Agitation *  0/53 (0.00%)  3/53 (5.66%)  0/7 (0.00%)  0/22 (0.00%) 
Anxiety *  3/53 (5.66%)  3/53 (5.66%)  0/7 (0.00%)  0/22 (0.00%) 
Confusion *  0/53 (0.00%)  3/53 (5.66%)  0/7 (0.00%)  0/22 (0.00%) 
Depression *  1/53 (1.89%)  5/53 (9.43%)  0/7 (0.00%)  2/22 (9.09%) 
Insomnia *  4/53 (7.55%)  5/53 (9.43%)  1/7 (14.29%)  0/22 (0.00%) 
Renal and urinary disorders         
Renal and urinary disorders, other *  0/53 (0.00%)  0/53 (0.00%)  1/7 (14.29%)  0/22 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Allergic rhinitis *  3/53 (5.66%)  3/53 (5.66%)  1/7 (14.29%)  0/22 (0.00%) 
Cough *  4/53 (7.55%)  4/53 (7.55%)  1/7 (14.29%)  0/22 (0.00%) 
Dyspnea *  8/53 (15.09%)  8/53 (15.09%)  0/7 (0.00%)  3/22 (13.64%) 
Pneumonitis *  3/53 (5.66%)  0/53 (0.00%)  0/7 (0.00%)  0/22 (0.00%) 
Respiratory, thoracic and mediastinal disorders - Other *  0/53 (0.00%)  3/53 (5.66%)  0/7 (0.00%)  0/22 (0.00%) 
Skin and subcutaneous tissue disorders         
Alopecia *  2/53 (3.77%)  8/53 (15.09%)  2/7 (28.57%)  0/22 (0.00%) 
Rash maculo-papular *  2/53 (3.77%)  5/53 (9.43%)  1/7 (14.29%)  0/22 (0.00%) 
Skin and subcutaneous tissue disorders - Other *  6/53 (11.32%)  4/53 (7.55%)  0/7 (0.00%)  2/22 (9.09%) 
Vascular disorders         
Hypertension *  2/53 (3.77%)  3/53 (5.66%)  0/7 (0.00%)  0/22 (0.00%) 
Hypotension *  3/53 (5.66%)  4/53 (7.55%)  0/7 (0.00%)  2/22 (9.09%) 
Thromboembolic event *  4/53 (7.55%)  3/53 (5.66%)  1/7 (14.29%)  0/22 (0.00%) 
Vascular disorders - Other *  1/53 (1.89%)  3/53 (5.66%)  0/7 (0.00%)  0/22 (0.00%) 
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Hedy Kindler, MD
Organization: University of Chicago
Phone: 773-702-0360
EMail: hkindler@medicine.bsd.uchicago.edu
Layout table for additonal information
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01064622     History of Changes
Other Study ID Numbers: NCI-2011-01454
NCI-2011-01454 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
8418
UCCRC-8418
CDR0000655378
09-068 ( Other Identifier: University of Chicago )
8418 ( Other Identifier: CTEP )
N01CM00071 ( U.S. NIH Grant/Contract )
P30CA014599 ( U.S. NIH Grant/Contract )
N01CM00038 ( U.S. NIH Grant/Contract )
First Submitted: February 5, 2010
First Posted: February 8, 2010
Results First Submitted: January 29, 2015
Results First Posted: February 13, 2015
Last Update Posted: August 14, 2015