EVA: Evaluation of Votrient in Angiosarcoma
Study Details
Study Description
Brief Summary
Open-label phase II trial investigating the efficacy and safety of the investigational combination of pazopanib and paclitaxel.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 2 |
Detailed Description
Open-label phase II trial investigating the efficacy and safety of the investigational combination of pazopanib and paclitaxel.This multi-center, open-label, prospective, single arm phase II study was designed to evaluate the clinical efficacy and safety of the experimental combination of pazopanib with paclitaxel in the treatment of patients with advanced or metastatic angiosarcoma.The safety evaluations (physical examination, laboratory checks as defined in protocol, toxicity/adverse event assessment according Eastern Cooperative Oncology Group version 4.0) are scheduled every cycle at day 1, 8, 15 and 29 (= day 1 of the next cycle).
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Pazopanib + Paclitaxel Paclitaxel administered every 28 days at day 1, day 8 and day 15 as a 2h intravenous infusion in a dose of 70mg/m2 in combination with pazopanib in a daily oral dose of 800mg (2x400mg) |
Drug: Pazopanib + Paclitaxel
pazopanib in combination with paclitaxel in the treatment of patients with advanced or metastatic angiosarcoma.
|
Outcome Measures
Primary Outcome Measures
- Rate of Progression-free Survival [6 Month]
The diagnosis of progession is based on tumor measurements assessed 182 days +/- 32 days after start of treatment (with imaging date as reference date) and according to the RECIST Version 1.1 criteria based on a predefined set of target lesions and non-target lesions.
- Rate of Progression-free Survival, Subgroup 1 Analysis [6 months]
Rate of progression-free survival for Subgroup 1 categorizing the 12 participants who showed PFS after 6 months into cutaneous angiosarcoma versus visceral angiosarcoma The diagnosis of progession is based on tumor measurements assessed 182 days +/- 32 days after start of treatment (with imaging date as reference date) and according to the RECIST Version 1.1 criteria based on a predefined set of target lesions and non-target lesions.
- Rate of Progression-free Survival, Subgroup 2 Analysis [6 months]
Rate of progression-free survival for Subgroup 1 categorizing the 12 participants who showed PFS after 6 months into primary angiosarcoma versus secondary angiosarcoma. The diagnosis of progession is based on tumor measurements assessed 182 days +/- 32 days after start of treatment (with imaging date as reference date) and according to the RECIST Version 1.1 criteria based on a predefined set of target lesions and non-target lesions.
Secondary Outcome Measures
- Overall Survival [from start of treatment until death within study's actual observation time for OS (22 months).]
Survival time of patient from start of treatment until death
- Overall Survival, Subgroup 1 Analysis [from start of treatment until death within study's actual observation time for OS (22 months)]
Survival time of patients from start of treatment until death, Subgroup 1 categorizing 26 overall participants into 18 cutaneous angiosarcoma versus 8 visceral angiosarcomas
- Overall Survival, Subgroup 2 Analysis [from start of treatment until death within study's actual observation time for OS (22 months)]
Survival time of patients from start of treatment until death, Subgroup 2 categorizing 26 overall participants into 13 primary cutaneous angiosarcoma versus 13 secondary angiosarcomas
- Response Rate (RR) [determined every 8 weeks during first 6 month then every 12 weeks in follow-up period until progression or death or end of overall study observation period (22 months), then evaluated as BOR]
Measurable skin lesions will be evaluated clinically and documented photographically, all other target lesions will be evaluated radiologically by CT or MRI according to RECIST Version 1.1. RR is given as 'Best overall response" BOR" defined as CR (complete remission), PR (partial) remission), SD (stable diesease) and PD (progressive disease) or NE (not evaluated) and provided by absolute and relative frequencies
- Response Rate (RR), Subgroup1 Analysis [determined every 8 weeks during first 6 month then every 12 weeks in follow-up period until progression or death or end of overall study observation period (22 months), then evaluated as BOR]
Measurable skin lesions will be evaluated clinically and documented photographically, all other target lesions will be evaluated radiologically by CT or MRI according to RECIST Version 1.1. RR is given as 'Best overall response" BOR" defined as CR (complete remission), PR (partial) remission), SD (stable diesease) and PD (progressive disease) or NE (not evaluated) and provided by absolute and relative frequencies for Subgroup 1 which is the analysis of cutaneous angiosarcoma versus visceral angiosarcoma
- Response Rate (RR), Subgroup 2 Analysis [determined every 8 weeks during first 6 month then every 12 weeks in follow-up period until progression or death or end of overall study observation period (22 months), then evaluated as BOR]
Measurable skin lesions will be evaluated clinically and documented photographically, all other target lesions will be evaluated radiologically by CT or MRI according to RECIST Version 1.1. RR is given as 'Best overall response" BOR" defined as CR (complete remission), PR (partial) remission), SD (stable diesease) and PD (progressive disease) or NE (not evaluated) and provided by absolute and relative frequencies for Subgroup 2 which is the analysis of primary angiosarcoma versus secondary angiosarcoma
- Adverse Events and Serious Adverse Events [30 days after EOS of last patient or end of overall study observation period (22 months)]
Number of patients in which adverse events occur during treatment according to Common Toxicity Criteria for Adverse Effects, Version 4.0
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Subjects must provide written informed consent prior to performance of study-specific procedures or assessments and must be willing to comply with treatment and follow-up. Note: Procedures conducted as part of the subject's routine clinical management (e.g., blood count, imaging studies) and obtained prior to signing informed consent may be utilized for screening or baseline purposes provided these procedures are conducted as specified in the protocol.
-
Age ≥ 18 years
-
Life expectancy > 3 months
-
Ability to swallow tablets
-
Histological confirmed angiosarcoma, primary and secondary angiosarcoma (e.g. radiation-induced or angiosarcoma in chronical lymphedema) are eligible.
-
Tumor must be locally advanced (unresectable) or metastatic. A progression must be documented within a 6-month period prior to screening.
-
Eastern Cooperative Oncology Group performance status ≤ 2
-
At least one measurable skin lesion or one measurable radiological (CT or MRI) target lesion (RECIST 1.1)
-
Adequate organ system function as described in protocol
-
A female is eligible to enter and participate in this study if she is either of non childbearing potential (defined in protocol) or childbearing potential with negative pregnancy test within 2 weeks prior to the first dose of study drug and agrees to use adequate contraception (as defined in protocol) during the study and for 30 days after the last dose of study drug.
-
All sexually active male patients must agree to use adequate methods of birth control (see protocol) throughout the study and for 30 days after the last dose of study drug.
Exclusion Criteria:
-
Patients who need an active treatment for another malignant disease other than angiosarcoma
-
Prior treatment with taxane within the last 12 months before study entry
-
History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal sarcomatosis.(see protocol)
-
Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding (see protocol)
-
Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product (see protocol)
-
Presence of uncontrolled infection
-
QT prolongation interval (QTc) > 480 msec.
-
Clinically significant cardiovascular disorders within the past 6 months
-
Major surgery or trauma within 28 days prior to first dose of investigational product and/or presence of any non-healing wound, fracture, or ulcer
-
Poorly controlled hypertension (see protocol)
-
Evidence of active bleeding or bleeding diathesis
-
Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels
-
Uncontrolled seizures, disorders of the CNS or psychiatric disorders which may put patient safety at risk, prevent giving informed consent or impact the patient's compliance with the use of study medication
-
Women who are pregnant or breast feeding
-
Patients who are not able or not willing to interrupt the intake of medications that are not allowed according to study protocol for at least 14 days before start of study medication and for the whole study period
-
Chemotherapy or radiotherapy within 14 days before start of study medication
-
Any ongoing toxicity from prior anti-cancer therapy that is > grade 1 and/or that is progressing in severity, except alopecia
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Universitätsklinik Graz | Graz | Austria | ||
2 | Universitätsklinik Wien | Wien | Austria | ||
3 | Helios-Klinikum Bad Saarow | Bad Saarow | Germany | ||
4 | Helios Klinikum Berlin-Buch | Berlin | Germany | ||
5 | Universitätsklinikum Carl Gustav Carus | Dresden | Germany | ||
6 | Universitätsklinikum Essen | Essen | Germany | ||
7 | Universitätsklinikum Hamburg-Eppendorf | Hamburg | Germany | ||
8 | Medizinische Hochschule Hannover | Hannover | Germany | ||
9 | University Medical Center | Mannheim | Germany | ||
10 | Klinikum der Universität München Campus Großhadern | München | Germany |
Sponsors and Collaborators
- Heidelberg University
- Universitätsmedizin Mannheim
- Helios Klinikum Berlin-Buch
- University Hospital Dresden
- Universitätsklinikum Hamburg-Eppendorf
- University Hospital, Essen
- Hannover Medical School
- Klinikum der Universitaet Muenchen, Grosshadern
- Medical University of Vienna
- Medical University of Graz
- Medical University Innsbruck
- Novartis Pharmaceuticals
Investigators
- Principal Investigator: Peter Hohenberger, MD, Universitätsmedizin Mannheim / Heidelberg University
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.- GISG-06
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Pazopanib + Paclitaxel |
---|---|
Arm/Group Description | Paclitaxel administered every 28 days at day 1, day 8 and day 15 as a 2h intravenous infusion in a dose of 70mg/m2 in combination with pazopanib in a daily oral dose of 800mg (2x400mg) in the treatment of patients with advanced or metastatic angiosarcoma. |
Period Title: Overall Study | |
STARTED | 26 |
COMPLETED | 25 |
NOT COMPLETED | 1 |
Baseline Characteristics
Arm/Group Title | Pazopanib + Paclitaxel |
---|---|
Arm/Group Description | Paclitaxel administered every 28 days at day 1, day 8 and day 15 as a 2h intravenous infusion in a dose of 70mg/m2 in combination with pazopanib in a daily oral dose of 800mg (2x400mg) Pazopanib + Paclitaxel: pazopanib in combination with paclitaxel in the treatment of patients with advanced or metastatic angiosarcoma. |
Overall Participants | 26 |
Age (years) [Mean (Standard Deviation) ] | |
Mean (Standard Deviation) [years] |
57.8
(13.5)
|
Sex: Female, Male (Count of Participants) | |
Female |
23
88.5%
|
Male |
3
11.5%
|
Race and Ethnicity Not Collected (Count of Participants) | |
Subgroup 1 for Analyses (Count of Participants) | |
cutaneous angiosarcoma |
18
69.2%
|
visceral angiosarcoma |
8
30.8%
|
Subgroup 2 for Analyses (Count of Participants) | |
primary angiosarcoma |
13
50%
|
secondary angiosarcoma |
13
50%
|
Outcome Measures
Title | Rate of Progression-free Survival |
---|---|
Description | The diagnosis of progession is based on tumor measurements assessed 182 days +/- 32 days after start of treatment (with imaging date as reference date) and according to the RECIST Version 1.1 criteria based on a predefined set of target lesions and non-target lesions. |
Time Frame | 6 Month |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Pazopanib + Paclitaxel |
---|---|
Arm/Group Description | Paclitaxel i.v. infusion over 6 cycles, administered on day 1, day 8, day 15 of every cycle with a dosage of 70mg/m2 in combination with Pazopanib taken orally with a dosage of 800mg daily/once per day Pazopanib + Paclitaxel: pazopanib in combination with paclitaxel in the treatment of patients with advanced or metastatic angiosarcoma. |
Measure Participants | 26 |
Count of Participants [Participants] |
12
46.2%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Pazopanib + Paclitaxel |
---|---|---|
Comments | Question is, if 6 months progression free survival rate (PFS-R) denoted by pPFS is higher than 35%. Test hypothesis is thus formulated as: H0: pPFS ≤0.35 versus H1: pPFS ≥0.35. This hypothesis is tested at the one-side significance level of 0.05. A 6 months PFS-R of 0.55 of cases or more is considered as clinically relevant success rate. The design is chosen such that rates of 0.55 or higher can be detected with a power of at least 0.8. | |
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Rate |
Estimated Value | 0.46 | |
Confidence Interval |
(2-Sided) % to |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Rate of Progression-free Survival, Subgroup 1 Analysis |
---|---|
Description | Rate of progression-free survival for Subgroup 1 categorizing the 12 participants who showed PFS after 6 months into cutaneous angiosarcoma versus visceral angiosarcoma The diagnosis of progession is based on tumor measurements assessed 182 days +/- 32 days after start of treatment (with imaging date as reference date) and according to the RECIST Version 1.1 criteria based on a predefined set of target lesions and non-target lesions. |
Time Frame | 6 months |
Outcome Measure Data
Analysis Population Description |
---|
Subgroup 1 (categorizing total number of 12 participants showing PFR survival after 6 months into cutaneous AS versus visceral AS) |
Arm/Group Title | Pazopanib + Paclitaxel |
---|---|
Arm/Group Description | Paclitaxel i.v. infusion over 6 cycles, administered on day 1, day 8, day 15 of every cycle with a dosage of 70mg/m2 in combination with Pazopanib taken orally with a dosage of 800mg daily/once per day in the treatment of patients with advanced or metastatic angiosarcoma. |
Measure Participants | 12 |
cutaneous angiosarcoma |
11
42.3%
|
visceral angiosarcoma |
1
3.8%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Pazopanib + Paclitaxel |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Rate difference |
Estimated Value | 0.486 | |
Confidence Interval |
(2-Sided) % to |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Rate of Progression-free Survival, Subgroup 2 Analysis |
---|---|
Description | Rate of progression-free survival for Subgroup 1 categorizing the 12 participants who showed PFS after 6 months into primary angiosarcoma versus secondary angiosarcoma. The diagnosis of progession is based on tumor measurements assessed 182 days +/- 32 days after start of treatment (with imaging date as reference date) and according to the RECIST Version 1.1 criteria based on a predefined set of target lesions and non-target lesions. |
Time Frame | 6 months |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Pazopanib + Paclitaxel |
---|---|
Arm/Group Description | Paclitaxel i.v. infusion over 6 cycles, administered on day 1, day 8, day 15 of every cycle with a dosage of 70mg/m2 in combination with Pazopanib taken orally with a dosage of 800mg daily/once per day in the treatment of patients with advanced or metastatic angiosarcoma. |
Measure Participants | 12 |
primary angiosarcoma |
6
23.1%
|
secondary angiosarcoma |
6
23.1%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Pazopanib + Paclitaxel |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Rate difference |
Estimated Value | 0 | |
Confidence Interval |
(2-Sided) % to |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Overall Survival |
---|---|
Description | Survival time of patient from start of treatment until death |
Time Frame | from start of treatment until death within study's actual observation time for OS (22 months). |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Pazopanib + Paclitaxel |
---|---|
Arm/Group Description | Paclitaxel administered every 28 days at day 1, day 8 and day 15 as a 2h intravenous infusion in a dose of 70mg/m2 in combination with pazopanib in a daily oral dose of 800mg (2x400mg) Pazopanib + Paclitaxel: pazopanib in combination with paclitaxel in the treatment of patients with advanced or metastatic angiosarcoma. |
Measure Participants | 26 |
Median (95% Confidence Interval) [months] |
21.6
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Pazopanib + Paclitaxel |
---|---|---|
Comments | The analysis of secondary endpoints is of descriptive nature and generally consists of summary statistics and interval estimation. Overall survival (OS) was defined as the time of start of treatment until death (event status=1) or last contact (censoring, event status=0). OS was analyzed using Kaplan-Meier curves. Median survival time is provided alonsgside two-sided 95% confidence interval (CI), if possible. | |
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Median |
Estimated Value | 21.6 | |
Confidence Interval |
(2-Sided) % to |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Overall Survival, Subgroup 1 Analysis |
---|---|
Description | Survival time of patients from start of treatment until death, Subgroup 1 categorizing 26 overall participants into 18 cutaneous angiosarcoma versus 8 visceral angiosarcomas |
Time Frame | from start of treatment until death within study's actual observation time for OS (22 months) |
Outcome Measure Data
Analysis Population Description |
---|
Overall number of participants analyzed is 26. Thereof, 18 show cutaneous angiosarcoma, and 8 show cutaneos angiosarcoma. |
Arm/Group Title | Pazopanib + Paclitaxel |
---|---|
Arm/Group Description | Paclitaxel i.v. infusion over 6 cycles, administered on day 1, day 8, day 15 of every cycle with a dosage of 70mg/m2 in combination with Pazopanib taken orally with a dosage of 800mg daily/once per day in the treatment of patients with advanced or metastatic angiosarcoma. |
Measure Participants | 26 |
cutaneous angiosarcoma |
21.6
|
visceral angiosaroma |
20.5
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Pazopanib + Paclitaxel |
---|---|---|
Comments | The analysis of secondary endpoints is of descriptive nature and generally consists of summary statistics and interval estimation. Overall survival (OS) for subgroup 1 was defined as the time of start of treatment until death (event status=1) or last contact (censoring, event status=0). OS was analyzed using Kaplan-Meier curves. Median survival time is provided alonsgside two-sided 95% confidence interval (CI), if possible. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.752 |
Comments | ||
Method | Log Rank | |
Comments |
Title | Overall Survival, Subgroup 2 Analysis |
---|---|
Description | Survival time of patients from start of treatment until death, Subgroup 2 categorizing 26 overall participants into 13 primary cutaneous angiosarcoma versus 13 secondary angiosarcomas |
Time Frame | from start of treatment until death within study's actual observation time for OS (22 months) |
Outcome Measure Data
Analysis Population Description |
---|
Overall number of participants analyzed is 26. Thereof, 13 show cutaneous angiosarcoma, and 13 show cutaneos angiosarcoma |
Arm/Group Title | Pazopanib + Paclitaxel |
---|---|
Arm/Group Description | Paclitaxel i.v. infusion over 6 cycles, administered on day 1, day 8, day 15 of every cycle with a dosage of 70mg/m2 in combination with Pazopanib taken orally with a dosage of 800mg daily/once per day in the treatment of patients with advanced or metastatic angiosarcoma. |
Measure Participants | 26 |
primary angiosarcoma |
20.5
|
secondary angiosarcoma |
21.6
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Pazopanib + Paclitaxel |
---|---|---|
Comments | The analysis of secondary endpoints is of descriptive nature and generally consists of summary statistics and interval estimation. Overall survival (OS) for subgroup 2 was defined as the time of start of treatment until death (event status=1) or last contact (censoring, event status=0). OS was analyzed using Kaplan-Meier curves. Median survival time is provided alonsgside two-sided 95% confidence interval (CI), if possible. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.621 |
Comments | ||
Method | Log Rank | |
Comments |
Title | Response Rate (RR) |
---|---|
Description | Measurable skin lesions will be evaluated clinically and documented photographically, all other target lesions will be evaluated radiologically by CT or MRI according to RECIST Version 1.1. RR is given as 'Best overall response" BOR" defined as CR (complete remission), PR (partial) remission), SD (stable diesease) and PD (progressive disease) or NE (not evaluated) and provided by absolute and relative frequencies |
Time Frame | determined every 8 weeks during first 6 month then every 12 weeks in follow-up period until progression or death or end of overall study observation period (22 months), then evaluated as BOR |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Pazopanib + Paclitaxel |
---|---|
Arm/Group Description | Paclitaxel administered every 28 days at day 1, day 8 and day 15 as a 2h intravenous infusion in a dose of 70mg/m2 in combination with pazopanib in a daily oral dose of 800mg (2x400mg) in the treatment of patients with advanced or metastatic angiosarcoma. |
Measure Participants | 26 |
CR |
2
7.7%
|
PR |
7
26.9%
|
SD |
6
23.1%
|
PD |
10
38.5%
|
NE |
1
3.8%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Pazopanib + Paclitaxel |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Other Statistical Analysis | Frequency of each category is given |
Title | Response Rate (RR), Subgroup1 Analysis |
---|---|
Description | Measurable skin lesions will be evaluated clinically and documented photographically, all other target lesions will be evaluated radiologically by CT or MRI according to RECIST Version 1.1. RR is given as 'Best overall response" BOR" defined as CR (complete remission), PR (partial) remission), SD (stable diesease) and PD (progressive disease) or NE (not evaluated) and provided by absolute and relative frequencies for Subgroup 1 which is the analysis of cutaneous angiosarcoma versus visceral angiosarcoma |
Time Frame | determined every 8 weeks during first 6 month then every 12 weeks in follow-up period until progression or death or end of overall study observation period (22 months), then evaluated as BOR |
Outcome Measure Data
Analysis Population Description |
---|
Total number of participants analyzed is 26. Thereof, 18 show cutaneous AS, and 8 show visceral angiosarcoma |
Arm/Group Title | Pazopanib + Paclitaxel |
---|---|
Arm/Group Description | Paclitaxel i.v. infusion over 6 cycles, administered on day 1, day 8, day 15 of every cycle with a dosage of 70mg/m2 in combination with Pazopanib taken orally with a dosage of 800mg daily/once per day in the treatment of patients with advanced or metastatic angiosarcoma. |
Measure Participants | 26 |
CR |
2
7.7%
|
PR |
6
23.1%
|
SD |
4
15.4%
|
PD |
6
23.1%
|
NE |
0
0%
|
CR |
0
0%
|
PR |
1
3.8%
|
SD |
2
7.7%
|
PD |
4
15.4%
|
NE |
1
3.8%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Pazopanib + Paclitaxel |
---|---|---|
Comments | Response Rate (RR) is given as Best Overall Response (BOR) and given be absolute and relative frequencies. Categories of BOR are CR, PR, SD, PD and NE) | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.349 |
Comments | ||
Method | Chi squared test, exact | |
Comments | ||
Other Statistical Analysis | Response Rate (RR) is given as Best Overall Response (BOR) and given be absolute and relative frequencies applied to the total of 26 enrolled subjects.. Categories of BOR are CR, PR, SD, PD and NE). |
Title | Response Rate (RR), Subgroup 2 Analysis |
---|---|
Description | Measurable skin lesions will be evaluated clinically and documented photographically, all other target lesions will be evaluated radiologically by CT or MRI according to RECIST Version 1.1. RR is given as 'Best overall response" BOR" defined as CR (complete remission), PR (partial) remission), SD (stable diesease) and PD (progressive disease) or NE (not evaluated) and provided by absolute and relative frequencies for Subgroup 2 which is the analysis of primary angiosarcoma versus secondary angiosarcoma |
Time Frame | determined every 8 weeks during first 6 month then every 12 weeks in follow-up period until progression or death or end of overall study observation period (22 months), then evaluated as BOR |
Outcome Measure Data
Analysis Population Description |
---|
Total number of participants analyzed is 26. Thereof, 13 show primary angiosarcoma, and 13 show secondary angiosarcoma |
Arm/Group Title | Pazopanib + Paclitaxel |
---|---|
Arm/Group Description | Paclitaxel i.v. infusion over 6 cycles, administered on day 1, day 8, day 15 of every cycle with a dosage of 70mg/m2 in combination with Pazopanib taken orally with a dosage of 800mg daily/once per day in the treatment of patients with advanced or metastatic angiosarcoma. |
Measure Participants | 26 |
CR |
0
0%
|
PR |
5
19.2%
|
SD |
3
11.5%
|
PD |
5
19.2%
|
NE |
0
0%
|
CR |
2
7.7%
|
PR |
2
7.7%
|
SD |
3
11.5%
|
PD |
5
19.2%
|
NE |
1
3.8%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Pazopanib + Paclitaxel |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.385 |
Comments | ||
Method | Chi squared test, exact | |
Comments |
Title | Adverse Events and Serious Adverse Events |
---|---|
Description | Number of patients in which adverse events occur during treatment according to Common Toxicity Criteria for Adverse Effects, Version 4.0 |
Time Frame | 30 days after EOS of last patient or end of overall study observation period (22 months) |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Pazopanib + Paclitaxel |
---|---|
Arm/Group Description | Paclitaxel administered every 28 days at day 1, day 8 and day 15 as a 2h intravenous infusion in a dose of 70mg/m2 in combination with pazopanib in a daily oral dose of 800mg (2x400mg) in the treatment of patients with advanced or metastatic angiosarcoma. |
Measure Participants | 26 |
Patients with AEs |
25
96.2%
|
Patients with SAEs |
10
38.5%
|
Adverse Events
Time Frame | Adverse Events were collected over the study observation period which was 22 months | |
---|---|---|
Adverse Event Reporting Description | ||
Arm/Group Title | Pazopanib + Paclitaxel | |
Arm/Group Description | Paclitaxel i.v. infusion over 6 cycles, administered on day 1, day 8, day 15 of every cycle with a dosage of 70mg/m2 in combination with Pazopanib taken orally with a dosage of 800 mg daily/once per day in the treatment of patients with advanced or metastatic angiosarcoma. | |
All Cause Mortality |
||
Pazopanib + Paclitaxel | ||
Affected / at Risk (%) | # Events | |
Total | 1/26 (3.8%) | |
Serious Adverse Events |
||
Pazopanib + Paclitaxel | ||
Affected / at Risk (%) | # Events | |
Total | 10/26 (38.5%) | |
Blood and lymphatic system disorders | ||
Neutropenia | 1/26 (3.8%) | 1 |
Cardiac disorders | ||
Palpitation | 1/26 (3.8%) | 1 |
Tachycardia | 1/26 (3.8%) | 1 |
Gastrointestinal disorders | ||
Gastrointestinal bleeding | 1/26 (3.8%) | 1 |
General disorders | ||
Fever of unknown origin | 1/26 (3.8%) | 1 |
Reduced general condition | 2/26 (7.7%) | 2 |
Dehydration | 1/26 (3.8%) | 1 |
Hepatobiliary disorders | ||
ALT increased | 1/26 (3.8%) | 1 |
Bilirubin increased | 1/26 (3.8%) | 1 |
GOT increased | 1/26 (3.8%) | 1 |
GPT increased | 1/26 (3.8%) | 1 |
Infections and infestations | ||
Erysipelas | 1/26 (3.8%) | 1 |
Musculoskeletal and connective tissue disorders | ||
Pain in thoracic spine | 1/26 (3.8%) | 1 |
Nervous system disorders | ||
Lumbar spinal stenosis | 1/26 (3.8%) | 1 |
Respiratory, thoracic and mediastinal disorders | ||
Pleural effusion | 1/26 (3.8%) | 1 |
Pneumothorax | 1/26 (3.8%) | 1 |
Other (Not Including Serious) Adverse Events |
||
Pazopanib + Paclitaxel | ||
Affected / at Risk (%) | # Events | |
Total | 25/26 (96.2%) | |
Blood and lymphatic system disorders | ||
Anemia | 3/26 (11.5%) | 6 |
Leukopenia | 6/26 (23.1%) | 28 |
Neutropenia | 5/26 (19.2%) | 18 |
Cardiac disorders | ||
Tachycardia | 3/26 (11.5%) | 5 |
Gastrointestinal disorders | ||
Abdominal pain | 5/26 (19.2%) | 6 |
Diarrhea | 16/26 (61.5%) | 29 |
Emesis | 3/26 (11.5%) | 8 |
Meteorism | 2/26 (7.7%) | 2 |
Obstipation | 4/26 (15.4%) | 7 |
Stomatitis | 6/26 (23.1%) | 12 |
Nausea | 8/26 (30.8%) | 14 |
General disorders | ||
Reduced general condition | 2/26 (7.7%) | 2 |
Fever | 4/26 (15.4%) | 4 |
Pain foot | 4/26 (15.4%) | 4 |
Fatigue | 12/26 (46.2%) | 26 |
Mucositis | 4/26 (15.4%) | 6 |
Thoracical pain | 2/26 (7.7%) | 2 |
Oedema leg | 7/26 (26.9%) | 11 |
Hepatobiliary disorders | ||
ALT increased | 4/26 (15.4%) | 12 |
AST increased | 4/26 (15.4%) | 12 |
Bilirubin increased | 2/26 (7.7%) | 3 |
Infections and infestations | ||
Acute nasopharyngitis | 3/26 (11.5%) | 3 |
Erysipels | 2/26 (7.7%) | 2 |
Investigations | ||
Weight loss | 2/26 (7.7%) | 2 |
Metabolism and nutrition disorders | ||
Exsikkosis | 2/26 (7.7%) | 3 |
Musculoskeletal and connective tissue disorders | ||
Inappetance | 4/26 (15.4%) | 4 |
Dorsalgia | 3/26 (11.5%) | 3 |
Nervous system disorders | ||
Dysgeusia | 11/26 (42.3%) | 21 |
Headache | 5/26 (19.2%) | 6 |
Neuropathia | 8/26 (30.8%) | 8 |
Vertigo | 3/26 (11.5%) | 3 |
Product Issues | ||
Allergic reation to a drug | 2/26 (7.7%) | 2 |
Psychiatric disorders | ||
Insomnia | 2/26 (7.7%) | 2 |
Respiratory, thoracic and mediastinal disorders | ||
Bronchitis | 2/26 (7.7%) | 2 |
Epistaxis | 5/26 (19.2%) | 6 |
Dyspnoea | 2/26 (7.7%) | 4 |
Cough | 4/26 (15.4%) | 6 |
Skin and subcutaneous tissue disorders | ||
Alopecia | 8/26 (30.8%) | 9 |
Rash | 3/26 (11.5%) | 3 |
Erythema | 2/26 (7.7%) | 3 |
Hand-foot syndrome | 5/26 (19.2%) | 11 |
Nail dystrophia | 2/26 (7.7%) | 3 |
Vascular disorders | ||
Hypertension | 12/26 (46.2%) | 17 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE 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
Name/Title | Prof. Dr. med. Peter Hohenberger |
---|---|
Organization | Universität Heidelberg/Universitätsmedizin Mannheim |
Phone | +49 0621 383 2609 |
peter.hohenberger@umm.de |
- GISG-06