Trial Outcomes & Findings for Activity and Tolerability of Pazopanib in Advanced and/or Metastatic Liposarcoma. A Phase II Clinical Trial (NCT NCT01692496)
NCT ID: NCT01692496
Last Updated: 2020-07-23
Results Overview
The primary objective of this study is to evaluate the activity of Pazopanib in patients with advanced and/or metastatic liposarcoma by means of progression-free survival (PFS) assessed 12 weeks after start of treatment. (According the RECIST criteria 1.1 and central radiology review). Progression was defined according to RECIST criteria 1.1 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
52 participants
Primary outcome timeframe
12 weeks after start of treatment
Results posted on
2020-07-23
Participant Flow
From 2013 to 2018, advanced and/or metastatic liposarcoma patients were recruited across 12 centres from Spain and Germany.
Patients were clustered in two cohorts based on the liposarcoma type: * Cohort A: well differentiated liposarcoma * Cohort B: Myxoid/round cell liposarcoma Both cohorts were included in the single arm treatment: Pazopanib
Participant milestones
| Measure |
Pazopanib
Patients will receive oral pazopanib, 800mg once daily and treatment will continue until disease progression, development of unacceptable toxicity, noncompliance, withdrawal of consent by the patient or investigator decision.
Pazopanib: Patients will receive oral pazopanib, 800mg once daily and treatment will continue until disease progression, development of unacceptable toxicity, noncompliance, withdrawal of consent by the patient or investigator decision.
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|---|---|
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Overall Study
STARTED
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52
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Overall Study
3 Weeks Pazopanib (Per Protocol PP)
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50
|
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Overall Study
COMPLETED
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52
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Overall Study
NOT COMPLETED
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0
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Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Pazopanib
n=52 Participants
Patients will receive oral pazopanib, 800mg once daily and treatment will continue until disease progression, development of unacceptable toxicity, noncompliance, withdrawal of consent by the patient or investigator decision.
Pazopanib: Patients will receive oral pazopanib, 800mg once daily and treatment will continue until disease progression, development of unacceptable toxicity, noncompliance, withdrawal of consent by the patient or investigator decision.
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|---|---|
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Age, Continuous
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58.3 Years
STANDARD_DEVIATION 13.5 • n=52 Participants
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Sex: Female, Male
Female
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24 Participants
n=52 Participants
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Sex: Female, Male
Male
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28 Participants
n=52 Participants
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|
Region of Enrollment
Germany
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13 participants
n=52 Participants
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Region of Enrollment
Spain
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39 participants
n=52 Participants
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Height
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168.1 cm
STANDARD_DEVIATION 11.1 • n=52 Participants
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Body weight
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77.3 Kg
STANDARD_DEVIATION 14.2 • n=52 Participants
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Systolic pressure
|
132.5 mm Hg
STANDARD_DEVIATION 15.9 • n=52 Participants
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Diastolic pressure
|
78.8 mm Hg
STANDARD_DEVIATION 8.8 • n=52 Participants
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PRIMARY outcome
Timeframe: 12 weeks after start of treatmentPopulation: Per protocol population
The primary objective of this study is to evaluate the activity of Pazopanib in patients with advanced and/or metastatic liposarcoma by means of progression-free survival (PFS) assessed 12 weeks after start of treatment. (According the RECIST criteria 1.1 and central radiology review). Progression was defined according to RECIST criteria 1.1 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Outcome measures
| Measure |
Pazopanib
n=50 Participants
Patients will receive oral pazopanib, 800mg once daily and treatment will continue until disease progression, development of unacceptable toxicity, noncompliance, withdrawal of consent by the patient or investigator decision.
Pazopanib: Patients will receive oral pazopanib, 800mg once daily and treatment will continue until disease progression, development of unacceptable toxicity, noncompliance, withdrawal of consent by the patient or investigator decision.
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|---|---|
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Progression-free Survival (PFS) Assessed 12 Weeks After Start of Treatment
Cohort A
|
54.1 percentage of participants
Interval 38.0 to 70.2
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Progression-free Survival (PFS) Assessed 12 Weeks After Start of Treatment
Cohort B
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46.2 percentage of participants
Interval 19.1 to 73.3
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SECONDARY outcome
Timeframe: Imaging studies repeated every 6 weeks for the first 12 weeks and every 8 weeks up to 36 months.Population: Per protocol
Overall progression free survival will be computed from the date of start of treatment to the first documented date of progression or the date of death, whatever the cause. Patients alive and free from progression at the time of the analysis will be censored at the date of last follow-up.
Outcome measures
| Measure |
Pazopanib
n=50 Participants
Patients will receive oral pazopanib, 800mg once daily and treatment will continue until disease progression, development of unacceptable toxicity, noncompliance, withdrawal of consent by the patient or investigator decision.
Pazopanib: Patients will receive oral pazopanib, 800mg once daily and treatment will continue until disease progression, development of unacceptable toxicity, noncompliance, withdrawal of consent by the patient or investigator decision.
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|---|---|
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Overall Progression Free Survival (Median PFS)
Pazopanib
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12.14 Weeks
Interval 7.75 to 16.53
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Overall Progression Free Survival (Median PFS)
Cohort A
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15 Weeks
Interval 8.19 to 21.8
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Overall Progression Free Survival (Median PFS)
Cohort B
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10.29 Weeks
Interval 5.09 to 15.49
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SECONDARY outcome
Timeframe: 6 weeks and 12 weeksPopulation: Per protocol (PP)
Objective tumor response, measured according to the RECIST 1.1 criteria (central reviewing) at 6 and 12 weeks. Response criteria are essentially based on a set of measurable lesions identified at baseline as target lesions, and followed until disease progression. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by 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
Outcome measures
| Measure |
Pazopanib
n=50 Participants
Patients will receive oral pazopanib, 800mg once daily and treatment will continue until disease progression, development of unacceptable toxicity, noncompliance, withdrawal of consent by the patient or investigator decision.
Pazopanib: Patients will receive oral pazopanib, 800mg once daily and treatment will continue until disease progression, development of unacceptable toxicity, noncompliance, withdrawal of consent by the patient or investigator decision.
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|---|---|
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Percentage of Patients With Objective Tumor Response (OR)
6 weeks OR (PP population)
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8 Percentage of patients
Interval 0.5 to 15.5
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Percentage of Patients With Objective Tumor Response (OR)
12 weeks OR (PP population)
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4 Percentage of patients
Interval 1.4 to 9.4
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SECONDARY outcome
Timeframe: Every 12 weeks from disease progression up to 36 months.Population: Per protocol
It will be computed from the date of start of treatment to the date of death, whatever the cause. Patients alive or lost for follow-up at the time of the analysis will be censored at the date of last follow-up.
Outcome measures
| Measure |
Pazopanib
n=50 Participants
Patients will receive oral pazopanib, 800mg once daily and treatment will continue until disease progression, development of unacceptable toxicity, noncompliance, withdrawal of consent by the patient or investigator decision.
Pazopanib: Patients will receive oral pazopanib, 800mg once daily and treatment will continue until disease progression, development of unacceptable toxicity, noncompliance, withdrawal of consent by the patient or investigator decision.
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|---|---|
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Overall Survival (OS)
Cohort A
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70.43 Weeks
Interval 42.69 to 98.1
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Overall Survival (OS)
Cohort B
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71.29 Weeks
Interval 31.21 to 111.36
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Overall Survival (OS)
Pazopanib
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70.43 Weeks
Interval 44.92 to 95.94
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SECONDARY outcome
Timeframe: Imaging studies required to investigate known disease should be repeated every 6 weeks for the first 12 weeks and every 8 weeks up to 36 months.Population: Per population
Patients who achieve complete response (CR), partial response (PR), or stable disease (SD) for 6 months or more and an improvement of symptoms will be considered as having derived clinical benefit.
Outcome measures
| Measure |
Pazopanib
n=50 Participants
Patients will receive oral pazopanib, 800mg once daily and treatment will continue until disease progression, development of unacceptable toxicity, noncompliance, withdrawal of consent by the patient or investigator decision.
Pazopanib: Patients will receive oral pazopanib, 800mg once daily and treatment will continue until disease progression, development of unacceptable toxicity, noncompliance, withdrawal of consent by the patient or investigator decision.
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|---|---|
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Clinical Benefit Rate
Pazopanib
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26 Percentage of patients
Interval 13.8 to 38.2
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Clinical Benefit Rate
Cohort A
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32.4 Percentage of patients
Interval 17.3 to 47.5
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Clinical Benefit Rate
Cohort B
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7.7 Percentage of patients
Interval 6.8 to 22.2
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SECONDARY outcome
Timeframe: Imaging studies required to investigate known disease should be repeated every 6 weeks for the first 12 weeks and every 8 weeks up to 36 months. At patient progression confirmed by means RECIST criteria V 1.1Population: Per protocol with TTP and TTPp registered
GMI is the ratio between time to progression (TTP) with pazopanib (TTPp) divided by the TTPp-1 with the previous line of therapy. GMI index values higher than 1 indicate that Pazopanib treatment has an increased time to progression when compared to previous line of treatment. GMI index values lower than 1 indicate that Pazopanib treatment has a reduced time to progression when compared to previous line of treatment. Higher GMI values are associated to a better outcome.
Outcome measures
| Measure |
Pazopanib
n=37 Participants
Patients will receive oral pazopanib, 800mg once daily and treatment will continue until disease progression, development of unacceptable toxicity, noncompliance, withdrawal of consent by the patient or investigator decision.
Pazopanib: Patients will receive oral pazopanib, 800mg once daily and treatment will continue until disease progression, development of unacceptable toxicity, noncompliance, withdrawal of consent by the patient or investigator decision.
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|---|---|
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Growth Modulation Index (GMI)
Pazopanib
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0.4 Arbitrary units
Interval 0.1 to 18.6
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Growth Modulation Index (GMI)
Cohort A
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0.7 Arbitrary units
Interval 0.1 to 18.6
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Growth Modulation Index (GMI)
Cohort B
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0.2 Arbitrary units
Interval 0.1 to 1.1
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SECONDARY outcome
Timeframe: Every week during the first month, week 6, week 9, week 12, every 4 weeks until end of treatment and at the end of treatment visit (28 days after the end of treatment), up to 36 monthsPopulation: Intention to treat
The safety and tolerability of Pazopanib will be determined by means of type, incidence, severity, timing, seriousness, and relatedness; of reported adverse events (AEs), physical examinations, and laboratory tests. Toxicity will be graded and tabulated by the NCI-CTCAE v 4.0.
Outcome measures
| Measure |
Pazopanib
n=52 Participants
Patients will receive oral pazopanib, 800mg once daily and treatment will continue until disease progression, development of unacceptable toxicity, noncompliance, withdrawal of consent by the patient or investigator decision.
Pazopanib: Patients will receive oral pazopanib, 800mg once daily and treatment will continue until disease progression, development of unacceptable toxicity, noncompliance, withdrawal of consent by the patient or investigator decision.
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|---|---|
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Safety Profile (According CTCAE, Version 4.0)
AEs Pazopanib
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52 Patients
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Safety Profile (According CTCAE, Version 4.0)
AEs Cohort A
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37 Patients
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Safety Profile (According CTCAE, Version 4.0)
AEs Cohort B
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15 Patients
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Safety Profile (According CTCAE, Version 4.0)
related AEs Pazpanib
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46 Patients
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Safety Profile (According CTCAE, Version 4.0)
related AEs Cohort A
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33 Patients
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Safety Profile (According CTCAE, Version 4.0)
related AEs Cohort B
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13 Patients
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Safety Profile (According CTCAE, Version 4.0)
AE grade ≥3 Pazopanib
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26 Patients
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Safety Profile (According CTCAE, Version 4.0)
AE grade ≥3 Cohort A
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17 Patients
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Safety Profile (According CTCAE, Version 4.0)
AE grade ≥3 Cohort B
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9 Patients
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Safety Profile (According CTCAE, Version 4.0)
related-AE grade ≥3 Pazopanib
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16 Patients
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Safety Profile (According CTCAE, Version 4.0)
related-AE grade ≥3 Cohort A
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11 Patients
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Safety Profile (According CTCAE, Version 4.0)
related-AE grade ≥3 Cohort B
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5 Patients
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Safety Profile (According CTCAE, Version 4.0)
prior to treatment AE Pazopanib
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44 Patients
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Safety Profile (According CTCAE, Version 4.0)
prior to treatment AE Cohort A
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31 Patients
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Safety Profile (According CTCAE, Version 4.0)
prior to treatment AE Cohort B
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13 Patients
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Adverse Events
Pazopanib
Serious events: 14 serious events
Other events: 52 other events
Deaths: 35 deaths
Serious adverse events
| Measure |
Pazopanib
n=52 participants at risk
Patients will receive oral pazopanib, 800mg once daily and treatment will continue until disease progression, development of unacceptable toxicity, noncompliance, withdrawal of consent by the patient or investigator decision.
Pazopanib: Patients will receive oral pazopanib, 800mg once daily and treatment will continue until disease progression, development of unacceptable toxicity, noncompliance, withdrawal of consent by the patient or investigator decision.
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|---|---|
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Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Abscess of tumor mass
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1.9%
1/52 • Number of events 1 • AEs up to 30 days after administration of the last dose of study drug, approximately 36 months
Additionally to AEs and SAEs definitions, an abnormal objective test finding should be reported as an AE as follows: * test result associated with clinically significant symptoms * test result lead to a change in study dosing or discontinuation from the study, significant additional concomitant drug treatment or other therapy * test result leads to any of the outcomes included in the definition of a SAE * test result were considered to be an AE by the investigator
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Blood and lymphatic system disorders
ALT increased
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3.8%
2/52 • Number of events 3 • AEs up to 30 days after administration of the last dose of study drug, approximately 36 months
Additionally to AEs and SAEs definitions, an abnormal objective test finding should be reported as an AE as follows: * test result associated with clinically significant symptoms * test result lead to a change in study dosing or discontinuation from the study, significant additional concomitant drug treatment or other therapy * test result leads to any of the outcomes included in the definition of a SAE * test result were considered to be an AE by the investigator
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Blood and lymphatic system disorders
Anemia
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1.9%
1/52 • Number of events 1 • AEs up to 30 days after administration of the last dose of study drug, approximately 36 months
Additionally to AEs and SAEs definitions, an abnormal objective test finding should be reported as an AE as follows: * test result associated with clinically significant symptoms * test result lead to a change in study dosing or discontinuation from the study, significant additional concomitant drug treatment or other therapy * test result leads to any of the outcomes included in the definition of a SAE * test result were considered to be an AE by the investigator
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General disorders
Ascites
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1.9%
1/52 • Number of events 1 • AEs up to 30 days after administration of the last dose of study drug, approximately 36 months
Additionally to AEs and SAEs definitions, an abnormal objective test finding should be reported as an AE as follows: * test result associated with clinically significant symptoms * test result lead to a change in study dosing or discontinuation from the study, significant additional concomitant drug treatment or other therapy * test result leads to any of the outcomes included in the definition of a SAE * test result were considered to be an AE by the investigator
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General disorders
General status deterioration
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1.9%
1/52 • Number of events 1 • AEs up to 30 days after administration of the last dose of study drug, approximately 36 months
Additionally to AEs and SAEs definitions, an abnormal objective test finding should be reported as an AE as follows: * test result associated with clinically significant symptoms * test result lead to a change in study dosing or discontinuation from the study, significant additional concomitant drug treatment or other therapy * test result leads to any of the outcomes included in the definition of a SAE * test result were considered to be an AE by the investigator
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|
Gastrointestinal disorders
Gastrointestinal bleeding
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1.9%
1/52 • Number of events 1 • AEs up to 30 days after administration of the last dose of study drug, approximately 36 months
Additionally to AEs and SAEs definitions, an abnormal objective test finding should be reported as an AE as follows: * test result associated with clinically significant symptoms * test result lead to a change in study dosing or discontinuation from the study, significant additional concomitant drug treatment or other therapy * test result leads to any of the outcomes included in the definition of a SAE * test result were considered to be an AE by the investigator
|
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Cardiac disorders
Cardiac dysrhythmia
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1.9%
1/52 • Number of events 1 • AEs up to 30 days after administration of the last dose of study drug, approximately 36 months
Additionally to AEs and SAEs definitions, an abnormal objective test finding should be reported as an AE as follows: * test result associated with clinically significant symptoms * test result lead to a change in study dosing or discontinuation from the study, significant additional concomitant drug treatment or other therapy * test result leads to any of the outcomes included in the definition of a SAE * test result were considered to be an AE by the investigator
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|
Immune system disorders
Febrile neutropenia
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1.9%
1/52 • Number of events 1 • AEs up to 30 days after administration of the last dose of study drug, approximately 36 months
Additionally to AEs and SAEs definitions, an abnormal objective test finding should be reported as an AE as follows: * test result associated with clinically significant symptoms * test result lead to a change in study dosing or discontinuation from the study, significant additional concomitant drug treatment or other therapy * test result leads to any of the outcomes included in the definition of a SAE * test result were considered to be an AE by the investigator
|
|
General disorders
Fatigue
|
1.9%
1/52 • Number of events 1 • AEs up to 30 days after administration of the last dose of study drug, approximately 36 months
Additionally to AEs and SAEs definitions, an abnormal objective test finding should be reported as an AE as follows: * test result associated with clinically significant symptoms * test result lead to a change in study dosing or discontinuation from the study, significant additional concomitant drug treatment or other therapy * test result leads to any of the outcomes included in the definition of a SAE * test result were considered to be an AE by the investigator
|
|
General disorders
Pain
|
1.9%
1/52 • Number of events 1 • AEs up to 30 days after administration of the last dose of study drug, approximately 36 months
Additionally to AEs and SAEs definitions, an abnormal objective test finding should be reported as an AE as follows: * test result associated with clinically significant symptoms * test result lead to a change in study dosing or discontinuation from the study, significant additional concomitant drug treatment or other therapy * test result leads to any of the outcomes included in the definition of a SAE * test result were considered to be an AE by the investigator
|
|
Musculoskeletal and connective tissue disorders
Femure fracture
|
1.9%
1/52 • Number of events 1 • AEs up to 30 days after administration of the last dose of study drug, approximately 36 months
Additionally to AEs and SAEs definitions, an abnormal objective test finding should be reported as an AE as follows: * test result associated with clinically significant symptoms * test result lead to a change in study dosing or discontinuation from the study, significant additional concomitant drug treatment or other therapy * test result leads to any of the outcomes included in the definition of a SAE * test result were considered to be an AE by the investigator
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
1.9%
1/52 • Number of events 1 • AEs up to 30 days after administration of the last dose of study drug, approximately 36 months
Additionally to AEs and SAEs definitions, an abnormal objective test finding should be reported as an AE as follows: * test result associated with clinically significant symptoms * test result lead to a change in study dosing or discontinuation from the study, significant additional concomitant drug treatment or other therapy * test result leads to any of the outcomes included in the definition of a SAE * test result were considered to be an AE by the investigator
|
|
Cardiac disorders
Cardiac disorders
|
1.9%
1/52 • Number of events 1 • AEs up to 30 days after administration of the last dose of study drug, approximately 36 months
Additionally to AEs and SAEs definitions, an abnormal objective test finding should be reported as an AE as follows: * test result associated with clinically significant symptoms * test result lead to a change in study dosing or discontinuation from the study, significant additional concomitant drug treatment or other therapy * test result leads to any of the outcomes included in the definition of a SAE * test result were considered to be an AE by the investigator
|
|
Cardiac disorders
Myocardial infarction
|
1.9%
1/52 • Number of events 1 • AEs up to 30 days after administration of the last dose of study drug, approximately 36 months
Additionally to AEs and SAEs definitions, an abnormal objective test finding should be reported as an AE as follows: * test result associated with clinically significant symptoms * test result lead to a change in study dosing or discontinuation from the study, significant additional concomitant drug treatment or other therapy * test result leads to any of the outcomes included in the definition of a SAE * test result were considered to be an AE by the investigator
|
|
Blood and lymphatic system disorders
Bilirrubin increase
|
1.9%
1/52 • Number of events 1 • AEs up to 30 days after administration of the last dose of study drug, approximately 36 months
Additionally to AEs and SAEs definitions, an abnormal objective test finding should be reported as an AE as follows: * test result associated with clinically significant symptoms * test result lead to a change in study dosing or discontinuation from the study, significant additional concomitant drug treatment or other therapy * test result leads to any of the outcomes included in the definition of a SAE * test result were considered to be an AE by the investigator
|
|
General disorders
Uncontrolled pain
|
1.9%
1/52 • Number of events 1 • AEs up to 30 days after administration of the last dose of study drug, approximately 36 months
Additionally to AEs and SAEs definitions, an abnormal objective test finding should be reported as an AE as follows: * test result associated with clinically significant symptoms * test result lead to a change in study dosing or discontinuation from the study, significant additional concomitant drug treatment or other therapy * test result leads to any of the outcomes included in the definition of a SAE * test result were considered to be an AE by the investigator
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor progression
|
1.9%
1/52 • Number of events 1 • AEs up to 30 days after administration of the last dose of study drug, approximately 36 months
Additionally to AEs and SAEs definitions, an abnormal objective test finding should be reported as an AE as follows: * test result associated with clinically significant symptoms * test result lead to a change in study dosing or discontinuation from the study, significant additional concomitant drug treatment or other therapy * test result leads to any of the outcomes included in the definition of a SAE * test result were considered to be an AE by the investigator
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor debulking
|
1.9%
1/52 • Number of events 1 • AEs up to 30 days after administration of the last dose of study drug, approximately 36 months
Additionally to AEs and SAEs definitions, an abnormal objective test finding should be reported as an AE as follows: * test result associated with clinically significant symptoms * test result lead to a change in study dosing or discontinuation from the study, significant additional concomitant drug treatment or other therapy * test result leads to any of the outcomes included in the definition of a SAE * test result were considered to be an AE by the investigator
|
Other adverse events
| Measure |
Pazopanib
n=52 participants at risk
Patients will receive oral pazopanib, 800mg once daily and treatment will continue until disease progression, development of unacceptable toxicity, noncompliance, withdrawal of consent by the patient or investigator decision.
Pazopanib: Patients will receive oral pazopanib, 800mg once daily and treatment will continue until disease progression, development of unacceptable toxicity, noncompliance, withdrawal of consent by the patient or investigator decision.
|
|---|---|
|
General disorders
Adverse Events
|
100.0%
52/52 • AEs up to 30 days after administration of the last dose of study drug, approximately 36 months
Additionally to AEs and SAEs definitions, an abnormal objective test finding should be reported as an AE as follows: * test result associated with clinically significant symptoms * test result lead to a change in study dosing or discontinuation from the study, significant additional concomitant drug treatment or other therapy * test result leads to any of the outcomes included in the definition of a SAE * test result were considered to be an AE by the investigator
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60