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Gemcitabine With or Without Pazopanib in Treating Patients With Refractory Soft Tissue Sarcoma

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ClinicalTrials.gov Identifier: NCT01532687
Recruitment Status : Completed
First Posted : February 14, 2012
Results First Posted : February 9, 2021
Last Update Posted : February 9, 2021
Sponsor:
Collaborators:
Novartis Pharmaceuticals
Oregon Health and Science University
Information provided by (Responsible Party):
Christopher Ryan, OHSU Knight Cancer Institute

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Adult Alveolar Soft Part Sarcoma
Adult Angiosarcoma
Adult Desmoplastic Small Round Cell Tumor
Adult Epithelioid Hemangioendothelioma
Adult Epithelioid Sarcoma
Adult Extraskeletal Myxoid Chondrosarcoma
Adult Extraskeletal Osteosarcoma
Adult Fibrosarcoma
Adult Leiomyosarcoma
Adult Liposarcoma
Adult Malignant Peripheral Nerve Sheath Tumor
Adult Rhabdomyosarcoma
Adult Synovial Sarcoma
Adult Undifferentiated Pleomorphic Sarcoma
Malignant Adult Hemangiopericytoma
Recurrent Adult Soft Tissue Sarcoma
Sarcoma
Stage III Adult Soft Tissue Sarcoma AJCC v7
Stage IV Adult Soft Tissue Sarcoma AJCC v7
Interventions Drug: Gemcitabine
Drug: Gemcitabine Hydrochloride
Other: Laboratory Biomarker Analysis
Drug: Pazopanib
Drug: Pazopanib Hydrochloride
Other: Placebo Administration
Enrollment 54
Recruitment Details  
Pre-assignment Details Double-blinded randomization (1:1) was stratified by subtypes of sarcoma (liposarcoma vs. all other eligible soft tissue sarcoma subtypes). Patients were randomized to either experimental arm or placebo arm prior to starting treatment. Those who discontinued treatment on the placebo arm due to disease progression were eligible for treatment with open-label pazopanib (unblinded, cross-over treatment); those who developed disease progression on the Experimental arm (pazopanib arm) were not.
Arm/Group Title Gemcitabine Hydrochloride Plus Pazopanib Hydrochloride Gemcitabine Hydrochloride Plus Placebo
Hide Arm/Group Description

Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and pazopanib hydrochloride PO on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Gemcitabine: Given IV

Gemcitabine Hydrochloride: Given IV

Laboratory Biomarker Analysis: Correlative studies

Pazopanib: Given PO

Pazopanib Hydrochloride: Given PO

Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and placebo PO on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression may receive single-agent pazopanib hydrochloride PO daily. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Gemcitabine: Given IV

Gemcitabine Hydrochloride: Given IV

Laboratory Biomarker Analysis: Correlative studies

Pazopanib: Given PO

Pazopanib Hydrochloride: Given PO

Placebo Administration: Given PO

Period Title: Overall Study
Started 29 25
Crossover to Open-label Pazopanib [1] 0 14
Completed 15 [2] 23 [3]
Not Completed 14 2
Reason Not Completed
Death             2             0
Adverse Event             6             1
Withdrawal by Subject             1             0
Physician Decision             2             1
Protocol-defined delay > 3 weeks             3             0
[1]
Participants who progress, unblinded, and found treated with gemcitibine+placebo arm are eligible to crossover into pazopanib open-label treatment phase
[2]
Participants remain on treatment until time of progression and through the AE assessment period
[3]
Participants remain on treatment until time of progression
Arm/Group Title Gemcitabine Hydrochloride Plus Pazopanib Hydrochloride Gemcitabine Hydrochloride Plus Placebo Total
Hide Arm/Group Description

Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and pazopanib hydrochloride PO on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Gemcitabine: Given IV

Gemcitabine Hydrochloride: Given IV

Laboratory Biomarker Analysis: Correlative studies

Pazopanib: Given PO

Pazopanib Hydrochloride: Given PO

Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and placebo PO on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression may receive single-agent pazopanib hydrochloride PO daily. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Gemcitabine: Given IV

Gemcitabine Hydrochloride: Given IV

Laboratory Biomarker Analysis: Correlative studies

Pazopanib: Given PO

Pazopanib Hydrochloride: Given PO

Placebo Administration: Given PO

Total of all reporting groups
Overall Number of Baseline Participants 29 25 54
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 29 participants 25 participants 54 participants
63
(55 to 70)
56
(48 to 66)
60
(50.3 to 68)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 29 participants 25 participants 54 participants
Female
14
  48.3%
16
  64.0%
30
  55.6%
Male
15
  51.7%
9
  36.0%
24
  44.4%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 29 participants 25 participants 54 participants
Asian
1
   3.4%
0
   0.0%
1
   1.9%
White
25
  86.2%
24
  96.0%
49
  90.7%
Unknown/Not Reported
3
  10.3%
1
   4.0%
4
   7.4%
Histology  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 29 participants 25 participants 54 participants
Liposarcoma
9
  31.0%
7
  28.0%
16
  29.6%
Leiomyosarcoma (LMS)
9
  31.0%
5
  20.0%
14
  25.9%
Undifferentiated Pleomorphic Sarcoma (UPS)
3
  10.3%
5
  20.0%
8
  14.8%
Synovial Sarcoma
3
  10.3%
3
  12.0%
6
  11.1%
Other Sarcoma(s)
5
  17.2%
5
  20.0%
10
  18.5%
Number Prior Treatments  
Median (Full Range)
Unit of measure:  Treatments
Number Analyzed 29 participants 25 participants 54 participants
1
(1 to 3)
1
(1 to 3)
1
(1 to 3)
1.Primary Outcome
Title Progression-free Survival (PFS)
Hide Description Compared using a one-sided Gehan-Wilcoxon test stratified by sarcoma subtype. Kaplan-Meier estimates for each treatment arm will be presented with the estimated hazard ratios and their associated confidence intervals. Progression is defined using Response Evaluation Criteria in Solid Tumors (RECIST) v1.0 as at least a 20% increase in the sum of the longest diameters of target lesions (taking as reference the smallest sum on study) with an absolute increase of at least 5 mm (target lesions), or measurable increase in non-target lesions (unequivocal progression), or appearance of one or more new lesions.
Time Frame Calculated as the time from randomization to the first documented progression or death, whichever occurs first, or until time of last contact if no progression or death occurred, assessed up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants
Arm/Group Title Gemcitabine Hydrochloride Plus Pazopanib Hydrochloride Gemcitabine Hydrochloride Plus Placebo
Hide Arm/Group Description:

Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and pazopanib hydrochloride PO on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Gemcitabine: Given IV

Gemcitabine Hydrochloride: Given IV

Laboratory Biomarker Analysis: Correlative studies

Pazopanib: Given PO

Pazopanib Hydrochloride: Given PO

Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and placebo PO on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression may receive single-agent pazopanib hydrochloride PO daily. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Gemcitabine: Given IV

Gemcitabine Hydrochloride: Given IV

Laboratory Biomarker Analysis: Correlative studies

Pazopanib: Given PO

Pazopanib Hydrochloride: Given PO

Placebo Administration: Given PO

Overall Number of Participants Analyzed 29 25
Median (95% Confidence Interval)
Unit of Measure: months
All randomized Number Analyzed 29 participants 25 participants
4.5
(3.0 to 8.5)
1.6
(1.4 to 4.3)
Liposarcoma Number Analyzed 9 participants 7 participants
8.9 [1] 
(4.3 to NA)
1.5 [2] 
(1.0 to NA)
Other Sarcoma Number Analyzed 20 participants 18 participants
4.4
(3.0 to 8.8)
2.2
(1.4 to 4.6)
[1]
There were not sufficient events to define the upper limit of the confidence interval (two out of nine participants progressed)
[2]
Due to the small sample size (n = 7) the upper confidence limit was not estimable (did not cross the 50% line)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Gemcitabine Hydrochloride Plus Pazopanib Hydrochloride, Gemcitabine Hydrochloride Plus Placebo
Comments Statistical results are for the full randomized population (n = 54). The study was originally designed with overall one-sided alpha of 5%, where a total of 73 patients (36 in the gemcitabine + placebo arm, and 37 in the gemcitabine + pazopanib arm) were required to achieve 80% power to detect a 2.5 month increase in median PFS (a hazard ratio of 0.55) between the two treatment arms. Study was closed early by the sponsor due to slow accrual and funds and thus was under powered.
Type of Statistical Test Superiority
Comments Log-log plots revealed crossing of the curves at late time points, indicating a possible interaction between treatment arms over time. We used the Gehan-Wilcoxon test, which weights early differences between groups, to test whether there is a difference between the treatment arms early in the study.
Statistical Test of Hypothesis P-Value 0.017
Comments [Not Specified]
Method Gehan-Wilcoxon
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Gemcitabine Hydrochloride Plus Pazopanib Hydrochloride, Gemcitabine Hydrochloride Plus Placebo
Comments Comparison between the two arms for the liposarcoma subgroup
Type of Statistical Test Other
Comments Log-log plots revealed crossing of the curves at late time points, indicating a possible interaction between treatment arms over time. We used the Gehan-Wilcoxon test, which weights early differences between groups, to test whether there is a difference between the treatment arms early in the study.
Statistical Test of Hypothesis P-Value 0.195
Comments [Not Specified]
Method Gehan-Wilcoxon
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Gemcitabine Hydrochloride Plus Pazopanib Hydrochloride, Gemcitabine Hydrochloride Plus Placebo
Comments Statistical results are for the 'other' sarcoma subgroup (n = 38)
Type of Statistical Test Other
Comments Log-log plots revealed crossing of the curves at late time points, indicating a possible interaction between treatment arms over time. We used the Gehan-Wilcoxon test, which weights early differences between groups, to test whether there is a difference between the treatment arms early in the study.
Statistical Test of Hypothesis P-Value 0.079
Comments [Not Specified]
Method Gehan-Wilcoxon
Comments [Not Specified]
2.Secondary Outcome
Title Progression-free Survival (PFS) for a Sub-group of Patients Treated With Open-label Pazopanib Hydrochloride Following Administration of Gemcitabine Hydrochloride in the Cross-over Portion of This Study
Hide Description Participants who progress during treatment and are found to be part of the gemcitabine+placebo arm after unblinding are eligible to receive open-label pazopanib with gemcitabine. This is the crossover population. Statistical analysis is exploratory and requires sufficient crossover participants to assess Kaplan-Meier estimated hazard ratio and associated 95% confidence interval. This represents the participants second progression. In both cases progression is defined using Response Evaluation Criteria in Solid Tumors (RECIST) v1.0 as at least a 20% increase in the sum of the longest diameters of target lesions with an absolute increase of at least 5 mm (target lesions), or measurable increase in non-target lesions (unequivocal progression), or appearance of one or more new lesions. First progression uses the smallest sum on study as a reference; progression for the crossover population uses first progression measurements as the reference.
Time Frame Calculated as the time from receiving open-labeled pazopanib hydrochloride to the next documented progression or death whichever occurs first, assessed up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
Participants randomized to the gemcitabine + placebo arm who progressed and elected to receive gemcitibine + open-label pazopanib
Arm/Group Title Crossover From Gemcitabine + Placebo to Gemcitabine + Open-label Pazopanib
Hide Arm/Group Description:
Participants randomized to the gemcitabine + placebo arm who progressed can be moved into the crossover arm, receiving gemcitabine + open-label pazopanib
Overall Number of Participants Analyzed 14
Median (95% Confidence Interval)
Unit of Measure: months
3.0 [1] 
(1.3 to NA)
[1]
Due to the small sample size (n = 14) the upper confidence limit was not estimable (did not cross the 50% line)
3.Secondary Outcome
Title Percentage of Participants Achieving Best Overall Objective Response (CR+PR)
Hide Description Response is evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, where RECIST combines assessments for target, non-target and presence of new lesions. Best Overall Objective Response is the sum of all CR+PR divided by all randomized participants, where the strongest recorded response is used for the evaluation (CR>PR>SD>PD). Objective response (CR+PR) requires at least a 30% decrease in the sum of the largest diameter target lesions (with respective to the baseline sum); disappearance of all or persistence of one or more non-target lesions, maintenance of tumor marker levels above normal limits, and no new lesions. Estimated odds ratio of best overall objective response are reported with 95% confidence interval for the two histologic sarcoma subgroups (liposarcoma vs all other eligible soft tissue sarcoma subtypes). One-sided proportions test is used to determine whether best overall objective response is greater for the gemcitabine plus pazopanib group.
Time Frame Best overall objective response recorded from the start of treatment until disease progression/recurrence assessed up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants.
Arm/Group Title Gemcitabine Hydrochloride Plus Pazopanib Hydrochloride Gemcitabine Hydrochloride Plus Placebo
Hide Arm/Group Description:

Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and pazopanib hydrochloride PO on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Gemcitabine: Given IV

Gemcitabine Hydrochloride: Given IV

Laboratory Biomarker Analysis: Correlative studies

Pazopanib: Given PO

Pazopanib Hydrochloride: Given PO

Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and placebo PO on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression may receive single-agent pazopanib hydrochloride PO daily. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Gemcitabine: Given IV

Gemcitabine Hydrochloride: Given IV

Laboratory Biomarker Analysis: Correlative studies

Pazopanib: Given PO

Pazopanib Hydrochloride: Given PO

Placebo Administration: Given PO

Overall Number of Participants Analyzed 29 25
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
All randomized participants Number Analyzed 29 participants 25 participants
6.9
(0.9 to 22.8)
8.0
(1.0 to 26.0)
Liposarcoma participants Number Analyzed 9 participants 7 participants
22.2
(2.8 to 60)
0 [1] 
(NA to NA)
Other sarcoma participants Number Analyzed 20 participants 18 participants
0 [1] 
(NA to NA)
11.1
(1.4 to 34.7)
[1]
No participants achieved overall objective response, making the confidence interval not estimable
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Gemcitabine Hydrochloride Plus Pazopanib Hydrochloride, Gemcitabine Hydrochloride Plus Placebo
Comments Statistical results are for the full randomized population (n = 54). The study tests whether gemcitabine plus pazopanib is superior to gemcitabine plus placebo (one-sided proportion test with Yate's continuity correction)
Type of Statistical Test Superiority
Comments Analysis was not powered for secondary endpoints. Given the study closed early due to slow enrollment, we do not anticipate detecting a statistical difference between the two groups
Statistical Test of Hypothesis P-Value 0.5
Comments Yate's continuity correction was applied because of the number of subjects and successes (n = 4)
Method One-sided Proportions Test
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Gemcitabine Hydrochloride Plus Pazopanib Hydrochloride, Gemcitabine Hydrochloride Plus Placebo
Comments Statistical results are for the Liposarcoma group (n = 16). The study tests whether gemcitabine plus pazopanib is superior to gemcitabine plus placebo (one-sided proportion test with Yate's continuity correction). Analysis was not powered for the secondary endpoints. Given the study closed early due to slow enrollment we do not anticipate detecting a statistical difference between the groups.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3
Comments Yate's continuity correction was applied because of small number of participants (n = 16) and successes (n = 2).
Method One-sided Proportion Test
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Gemcitabine Hydrochloride Plus Pazopanib Hydrochloride, Gemcitabine Hydrochloride Plus Placebo
Comments Statistical results are for the Other Sarcoma group (n = 38). The study tests whether gemcitabine plus pazopanib is superior to gemcitabine plus placebo (one-sided proportion test with Yate's continuity correction). Analysis was not powered for secondary endpoints. Given the study closed early due to slow enrollment, we do not anticipate detecting a statistical difference between the two groups.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8
Comments Yate's continuity correction was applied because of the small number of participants and successes (n = 2).
Method One-sided Proportion Test
Comments [Not Specified]
4.Secondary Outcome
Title Overall Survival
Hide Description Two treatment arms will be compared using a one-sided log-rank test stratified by sarcoma subtype and study site. Kaplan-Meier estimates and the survival curves for each treatment arm will be presented with the estimated hazard ratios and their associated confidence interval.
Time Frame From randomization to death due to any cause, or until last patient contact if the patient did not die, assessed up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants
Arm/Group Title Gemcitabine Hydrochloride Plus Pazopanib Hydrochloride Gemcitabine Hydrochloride Plus Placebo
Hide Arm/Group Description:

Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and pazopanib hydrochloride PO on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Gemcitabine: Given IV

Gemcitabine Hydrochloride: Given IV

Laboratory Biomarker Analysis: Correlative studies

Pazopanib: Given PO

Pazopanib Hydrochloride: Given PO

Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and placebo PO on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression may receive single-agent pazopanib hydrochloride PO daily. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Gemcitabine: Given IV

Gemcitabine Hydrochloride: Given IV

Laboratory Biomarker Analysis: Correlative studies

Pazopanib: Given PO

Pazopanib Hydrochloride: Given PO

Placebo Administration: Given PO

Overall Number of Participants Analyzed 29 25
Median (95% Confidence Interval)
Unit of Measure: months
All Randomized Number Analyzed 29 participants 25 participants
11.0
(9.6 to 20.7)
15.6
(6.1 to 27.0)
Liposarcoma participants Number Analyzed 9 participants 7 participants
20.5 [1] 
(11.0 to NA)
5.7 [2] 
(3.5 to NA)
Other Sarcoma participants Number Analyzed 20 participants 18 participants
10.2
(7.6 to 20.7)
17.7
(7.6 to 30.7)
[1]
Upper limit was not estimable because there was no observed death time greater than the median survival that touched or crossed -1,96 using the log-transformation of the survival function (ref: Formula 4.5.5, Klein JP and Moeschberger ML, Survival Analysis: Techniques for censored and truncated data). This is likely due to small sample size (n = 9).
[2]
Upper limit was not estimable due to small sample size (n = 7) and failure to cross the 25% line.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Gemcitabine Hydrochloride Plus Pazopanib Hydrochloride, Gemcitabine Hydrochloride Plus Placebo
Comments Overall survival estimated among all randomized participants (n = 54)
Type of Statistical Test Other
Comments Log-log plots revealed crossing of the curves at late time points, indicating a possible interaction between treatment arms over time. We used the Gehan-Wilcoxon test, which weights early differences between groups, to test whether there is a difference between the treatment arms early in the study.
Statistical Test of Hypothesis P-Value 0.481
Comments [Not Specified]
Method Gehan-Wilcoxon
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Gemcitabine Hydrochloride Plus Pazopanib Hydrochloride, Gemcitabine Hydrochloride Plus Placebo
Comments Overall survival compared between the two arms for the liposarcoma subgroup (n = 16)
Type of Statistical Test Other
Comments Log-log plots revealed crossing of the curves at late time points, indicating a possible interaction between treatment arms over time. We used the Gehan-Wilcoxon test, which weights early differences between groups, to test whether there is a difference between the treatment arms early in the study.
Statistical Test of Hypothesis P-Value 0.353
Comments [Not Specified]
Method Gehan-Wilcoxon
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Gemcitabine Hydrochloride Plus Pazopanib Hydrochloride, Gemcitabine Hydrochloride Plus Placebo
Comments Overall survival comparison between the two treatment arms for the other sarcoma group (n = 38)
Type of Statistical Test Other
Comments Log-log plots revealed crossing of the curves at late time points, indicating a possible interaction between treatment arms over time. We used the Gehan-Wilcoxon test, which weights early differences between groups, to test whether there is a difference between the treatment arms early in the study.
Statistical Test of Hypothesis P-Value 0.408
Comments [Not Specified]
Method Gehan-Wilcoxon
Comments [Not Specified]
Time Frame Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months).
Adverse Event Reporting Description All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
 
Arm/Group Title Gemcitabine Hydrochloride Plus Pazopanib Hydrochloride Gemcitabine Hydrochloride Plus Placebo Crossover From Gemcitabine Plus Placebo to Gemcitabine Plus Open-label Pazopanib
Hide Arm/Group Description

Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and pazopanib hydrochloride PO on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Gemcitabine: Given IV

Gemcitabine Hydrochloride: Given IV

Laboratory Biomarker Analysis: Correlative studies

Pazopanib: Given PO

Pazopanib Hydrochloride: Given PO

Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and placebo PO on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression, are unblinded and found randomized to placebo arm may crossover to receive open-label pazopanib hydrochloride PO daily.

AEs and deaths reported only while participant is in placebo arm/group.

Gemcitabine: Given IV

Gemcitabine Hydrochloride: Given IV

Laboratory Biomarker Analysis: Correlative studies

Pazopanib: Given PO

Pazopanib Hydrochloride: Given PO

Placebo Administration: Given PO

Patients who progress and found randomized to the placebo arm after unblinding are eligible for receipt of open-label gemcitabine plus pazopanib. Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and pazopanib hydrochloride PO on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. AEs and deaths collected during this treatment period
All-Cause Mortality
Gemcitabine Hydrochloride Plus Pazopanib Hydrochloride Gemcitabine Hydrochloride Plus Placebo Crossover From Gemcitabine Plus Placebo to Gemcitabine Plus Open-label Pazopanib
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   23/29 (79.31%)   10/11 (90.91%)   11/14 (78.57%) 
Hide Serious Adverse Events
Gemcitabine Hydrochloride Plus Pazopanib Hydrochloride Gemcitabine Hydrochloride Plus Placebo Crossover From Gemcitabine Plus Placebo to Gemcitabine Plus Open-label Pazopanib
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   8/29 (27.59%)   6/25 (24.00%)   5/14 (35.71%) 
Blood and lymphatic system disorders       
Febrile neutropenia  1  1/29 (3.45%)  0/25 (0.00%)  0/14 (0.00%) 
Cardiac disorders       
Heart failure  1  2/29 (6.90%)  1/25 (4.00%)  1/14 (7.14%) 
Supraventricular tachycardia  1  0/29 (0.00%)  1/25 (4.00%)  0/14 (0.00%) 
Acute coronary syndrome  1  0/29 (0.00%)  1/25 (4.00%)  0/14 (0.00%) 
Atrial fibrillation  1  2/29 (6.90%)  0/25 (0.00%)  0/14 (0.00%) 
Gastrointestinal disorders       
Abdominal pain  1  0/29 (0.00%)  1/25 (4.00%)  1/14 (7.14%) 
Gastric perforation  1  0/29 (0.00%)  0/25 (0.00%)  1/14 (7.14%) 
Colitis  1  1/29 (3.45%)  0/25 (0.00%)  0/14 (0.00%) 
General disorders       
Pain  1  0/29 (0.00%)  0/25 (0.00%)  1/14 (7.14%) 
Fever  1  1/29 (3.45%)  0/25 (0.00%)  1/14 (7.14%) 
Edema limbs  1  1/29 (3.45%)  0/25 (0.00%)  0/14 (0.00%) 
Edema trunk  1  1/29 (3.45%)  0/25 (0.00%)  0/14 (0.00%) 
Hepatobiliary disorders       
Cholecystitis  1  0/29 (0.00%)  0/25 (0.00%)  1/14 (7.14%) 
Hepatic failure  1  1/29 (3.45%)  0/25 (0.00%)  0/14 (0.00%) 
Infections and infestations       
Skin infection  1  0/29 (0.00%)  1/25 (4.00%)  0/14 (0.00%) 
Lung infection  1  1/29 (3.45%)  1/25 (4.00%)  0/14 (0.00%) 
Investigations       
Alanine aminotransferase increased  1  2/29 (6.90%)  1/25 (4.00%)  0/14 (0.00%) 
Aspartate aminotransferase increased  1  2/29 (6.90%)  1/25 (4.00%)  0/14 (0.00%) 
Ejection fraction decreased  1  2/29 (6.90%)  0/25 (0.00%)  1/14 (7.14%) 
Cardiac troponin I increase  1  1/29 (3.45%)  0/25 (0.00%)  0/14 (0.00%) 
Neutrophil count decreased  1  1/29 (3.45%)  0/25 (0.00%)  0/14 (0.00%) 
Platelet count decreased  1  1/29 (3.45%)  0/25 (0.00%)  0/14 (0.00%) 
Metabolism and nutrition disorders       
Hypoglycemia  1  0/29 (0.00%)  1/25 (4.00%)  0/14 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Tumor pain  1  0/29 (0.00%)  0/25 (0.00%)  1/14 (7.14%) 
Renal and urinary disorders       
Proteinuria  1  0/29 (0.00%)  1/25 (4.00%)  0/14 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Dyspnea  1  1/29 (3.45%)  0/25 (0.00%)  1/14 (7.14%) 
Pleural effusion  1  0/29 (0.00%)  0/25 (0.00%)  1/14 (7.14%) 
Pneumothorax  1  1/29 (3.45%)  0/25 (0.00%)  0/14 (0.00%) 
Pulmonary edema  1  1/29 (3.45%)  0/25 (0.00%)  0/14 (0.00%) 
Vascular disorders       
Hypertension  1  1/29 (3.45%)  0/25 (0.00%)  0/14 (0.00%) 
Thromboembolic event  1  1/29 (3.45%)  0/25 (0.00%)  0/14 (0.00%) 
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 4%
Gemcitabine Hydrochloride Plus Pazopanib Hydrochloride Gemcitabine Hydrochloride Plus Placebo Crossover From Gemcitabine Plus Placebo to Gemcitabine Plus Open-label Pazopanib
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   25/29 (86.21%)   14/25 (56.00%)   9/14 (64.29%) 
Blood and lymphatic system disorders       
Anemia  1  2/29 (6.90%)  3/25 (12.00%)  0/14 (0.00%) 
Febrile neutropenia  1  2/29 (6.90%)  2/25 (8.00%)  0/14 (0.00%) 
Cardiac disorders       
Heart failure  1  2/29 (6.90%)  1/25 (4.00%)  1/14 (7.14%) 
Gastrointestinal disorders       
Abdominal pain  1  0/29 (0.00%)  1/25 (4.00%)  2/14 (14.29%) 
Diarrhea  1  2/29 (6.90%)  0/25 (0.00%)  0/14 (0.00%) 
Gastric perforation  1  0/29 (0.00%)  0/25 (0.00%)  1/14 (7.14%) 
General disorders       
Fatigue  1  2/29 (6.90%)  0/25 (0.00%)  2/14 (14.29%) 
Hepatobiliary disorders       
Cholecystitis  1  0/29 (0.00%)  0/25 (0.00%)  1/14 (7.14%) 
Investigations       
Alanine aminotransferase increased  1  3/29 (10.34%)  1/25 (4.00%)  0/14 (0.00%) 
Aspartate aminotransferase increased  1  2/29 (6.90%)  1/25 (4.00%)  0/14 (0.00%) 
Lymphocyte count decreased  1  4/29 (13.79%)  0/25 (0.00%)  0/14 (0.00%) 
Neutrophil count decreased  1  12/29 (41.38%)  9/25 (36.00%)  1/14 (7.14%) 
Platelet count decreased  1  4/29 (13.79%)  0/25 (0.00%)  0/14 (0.00%) 
White blood cell decreased  1  4/29 (13.79%)  1/25 (4.00%)  0/14 (0.00%) 
Ejection fraction decreased  1  2/29 (6.90%)  0/25 (0.00%)  1/14 (7.14%) 
Metabolism and nutrition disorders       
Hyperglycemia  1  2/29 (6.90%)  0/25 (0.00%)  0/14 (0.00%) 
Hypoalbuminemia  1  1/29 (3.45%)  1/25 (4.00%)  2/14 (14.29%) 
Hypophosphatemia  1  2/29 (6.90%)  0/25 (0.00%)  0/14 (0.00%) 
Hyponatremia  1  1/29 (3.45%)  0/25 (0.00%)  1/14 (7.14%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Tumor pain  1  0/29 (0.00%)  0/25 (0.00%)  1/14 (7.14%) 
Respiratory, thoracic and mediastinal disorders       
Dyspnea  1  1/29 (3.45%)  0/25 (0.00%)  1/14 (7.14%) 
Hypoxia  1  0/29 (0.00%)  0/25 (0.00%)  1/14 (7.14%) 
Pulmonary edema  1  0/29 (0.00%)  0/25 (0.00%)  1/14 (7.14%) 
Vascular disorders       
Hypertension  1  5/29 (17.24%)  0/25 (0.00%)  1/14 (7.14%) 
Thromboembolic event  1  3/29 (10.34%)  0/25 (0.00%)  0/14 (0.00%) 
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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
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Name/Title: Dr. Christopher Ryan
Organization: OHSU Knight Cancer Institute
Phone: 503-494-9000
EMail: ryanc@ohsu.edu
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Responsible Party: Christopher Ryan, OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier: NCT01532687    
Other Study ID Numbers: IRB00007943
NCI-2012-00052 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
IRB00007943 ( Other Identifier: OHSU Knight Cancer Institute )
First Submitted: February 6, 2012
First Posted: February 14, 2012
Results First Submitted: October 30, 2020
Results First Posted: February 9, 2021
Last Update Posted: February 9, 2021