Evaluation of Votrient in Angiosarcoma (EVA)

• ClinicalTrials.gov Identifier: NCT02212015
• Recruitment Status: Terminated
• First Posted: August 8, 2014
• Results First Posted: March 22, 2022
• Last Update Posted: March 22, 2022
• Sponsor: Heidelberg University
• Collaborators: 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
• Information provided by (Responsible Party): Peter Hohenberger, Universitätsmedizin Mannheim

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 (Clinical Trial)
• 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: July 2014
• Actual Primary Completion Date: December 31, 2019
• Actual Study Completion Date: July 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ 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 ]

   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 [ 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 ]

   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 [ 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 ]

   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 [ Time Frame: 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

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Austria

Universitätsklinik Graz

Graz, Austria

Universitätsklinik Wien

Wien, Austria

Germany

Helios-Klinikum Bad Saarow

Bad Saarow, Germany

Helios Klinikum Berlin-Buch

Berlin, Germany

Universitätsklinikum Carl Gustav Carus

Dresden, Germany

Universitätsklinikum Essen

Essen, Germany

Universitätsklinikum Hamburg-Eppendorf

Hamburg, Germany

Medizinische Hochschule Hannover

Hannover, Germany

University Medical Center

Mannheim, Germany

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)

Documents provided by Peter Hohenberger, Universitätsmedizin Mannheim:

Study Protocol  [PDF] January 28, 2016

Statistical Analysis Plan  [PDF] April 3, 2020

More Information

Additional Information:

German Interdisciplinary Sarcoma Group 

Sarcoma Platform Austria 

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

Additional relevant MeSH terms:

Hemangiosarcoma; Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Vascular Tissue; Paclitaxel; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action