Evaluation of Votrient in Angiosarcoma

Phase 2

Terminated

Conditions: Angiosarcoma

Interventions: Drug: Pazopanib + Paclitaxel

Registration Number: NCT02212015

Lead Sponsor: Heidelberg University

Brief Summary: Open-label phase II trial investigating the efficacy and safety of the investigational combination of pazopanib and paclitaxel.

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).

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 26

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Pazopanib + Paclitaxel	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)

Primary Outcome Measures

Name	Time	Method
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 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.
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.

Secondary Outcome Measures

Name	Time	Method
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
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
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), 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
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 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), 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

Trial Locations

Locations (10): Universitätsklinik Wien
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Wien, Austria
Helios-Klinikum Bad Saarow
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Bad Saarow, Germany
Helios Klinikum Berlin-Buch
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Berlin, Germany
Universitätsklinik Graz
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Graz, Austria
Universitätsklinikum Essen
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Essen, Germany
Universitätsklinikum Carl Gustav Carus
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Dresden, Germany
Universitätsklinikum Hamburg-Eppendorf
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Hamburg, Germany
Medizinische Hochschule Hannover
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Hannover, Germany
Klinikum der Universität München Campus Großhadern
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München, Germany
University Medical Center
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Mannheim, Germany