Clinical trial NCT02212015: Evaluation of Votrient in Angiosarcoma
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Angiosarcoma
Lead sponsor: Heidelberg University
Sponsor class: OTHER
Collaborators: name: Universitätsmedizin Mannheim
name: Helios Klinikum Berlin-Buch
name: University Hospital Dresden
name: Universitätsklinikum Hamburg-Eppendorf
name: University Hospital, Essen
name: Hannover Medical School
name: Klinikum der Universitaet Muenchen, Grosshadern
name: Medical University of Vienna
name: Medical University of Graz
name: Medical University Innsbruck
name: Novartis Pharmaceuticals
First posted: 2014-08-08
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

Eligibility 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

Primary outcomes:
measure: Rate of Progression-free Survival
timeFrame: 6 Month
measure: Rate of Progression-free Survival, Subgroup 1 Analysis
timeFrame: 6 months
measure: Rate of Progression-free Survival, Subgroup 2 Analysis
timeFrame: 6 months
Secondary outcomes:
measure: Overall Survival
timeFrame: from start of treatment until death within study's actual observation time for OS (22 months).
measure: Overall Survival, Subgroup 1 Analysis
timeFrame: from start of treatment until death within study's actual observation time for OS (22 months)
measure: Overall Survival, Subgroup 2 Analysis
timeFrame: from start of treatment until death within study's actual observation time for OS (22 months)
measure: Response Rate (RR)
timeFrame: 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
measure: Response Rate (RR), Subgroup1 Analysis
timeFrame: 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
measure: Response Rate (RR), Subgroup 2 Analysis
timeFrame: 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
measure: Adverse Events and Serious Adverse Events
timeFrame: 30 days after EOS of last patient or end of overall study observation period (22 months)
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Universitätsklinik Graz
city: Wien
country: Austria
facility: Universitätsklinik Wien
city: Bad Saarow
country: Germany
facility: Helios-Klinikum Bad Saarow
city: Berlin
country: Germany
facility: Helios Klinikum Berlin-Buch
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Mannheim
country: Germany
facility: University Medical Center
city: München
country: Germany
facility: Klinikum der Universität München Campus Großhadern
Study officials:
affiliation: Universitätsmedizin Mannheim / Heidelberg University
name: Peter Hohenberger, MD
role: PRINCIPAL_INVESTIGATOR
References: