EVA: Evaluation of Votrient in Angiosarcoma

• Sponsor: Heidelberg University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02212015
• Collaborator: Universitätsmedizin Mannheim (Other), Helios Klinikum Berlin-Buch (Other), University Hospital Dresden (Other), Universitätsklinikum Hamburg-Eppendorf (Other), University Hospital, Essen (Other), Hannover Medical School (Other), Klinikum der Universitaet Muenchen, Grosshadern (Other), Medical University of Vienna (Other), Medical University of Graz (Other), Medical University Innsbruck (Other), Novartis Pharmaceuticals (Industry)
• Enrollment: 26
• Locations: 10
• Arm: 1
• Duration (Months): 72
• Patients Per Site: 2.6
• Patients Per Site Per Month: 0

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
Angiosarcoma	Drug: Pazopanib + Paclitaxel	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

• Study Type: Interventional
• Actual Enrollment: 26 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Single-arm, Multicenter, Open Label Phase II Trial to Evaluate the Efficacy of Pazopanib in Combination With Paclitaxel in Advanced and Relapsed Angiosarcoma
• Study Start Date: Jul 1, 2014
• Actual Primary Completion Date: Dec 31, 2019
• Actual Study Completion Date: Jul 1, 2020

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

1. 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.

2. 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.

3. 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

1. 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

2. 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

3. 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

4. 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

5. 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

6. 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

7. 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

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

• Study Protocol - Jan 28, 2016
• Statistical Analysis Plan - Apr 3, 2020

More Information

Additional Information:

• German Interdisciplinary Sarcoma Group
• Sarcoma Platform Austria

Publications

None provided.

• Responsible Party: Peter Hohenberger, Prof. Dr. med., Universitätsmedizin Mannheim
• ClinicalTrials.gov Identifier: NCT02212015
• Other Study ID Numbers: GISG-06
• First Posted: Aug 8, 2014
• Last Update Posted: Mar 22, 2022
• Last Verified: Jan 1, 2022

• Additional relevant MeSH terms: Hemangiosarcoma; Paclitaxel

Study Results

Participant Flow

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

1. Primary Outcome

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

2. Primary Outcome

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

3. Primary Outcome

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

4. Secondary Outcome

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

5. Secondary Outcome

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

6. Secondary Outcome

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

7. Secondary Outcome

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

8. Secondary Outcome

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).

9. Secondary Outcome

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

10. Secondary Outcome

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
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

[Not Specified]

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.