Single-arm, Multicenter, Open Label Phase II Trial to Evaluate the Efficacy of Pazopanib in Combination With Paclitaxel in Advanced and Relapsed Angiosarcoma
Overview
- Phase
- Phase 2
- Intervention
- Pazopanib + Paclitaxel
- Conditions
- Angiosarcoma
- Sponsor
- Heidelberg University
- Enrollment
- 26
- Locations
- 10
- Primary Endpoint
- Rate of Progression-free Survival
- Status
- Terminated
- Last Updated
- 4 years ago
Overview
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).
Investigators
Peter Hohenberger
Prof. Dr. med.
Universitätsmedizin Mannheim
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.
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)
Arms & Interventions
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)
Intervention: Pazopanib + Paclitaxel
Outcomes
Primary Outcomes
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.
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.
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.
Secondary Outcomes
- Adverse Events and Serious Adverse Events(30 days after EOS of last patient or end of overall study observation period (22 months))
- Overall Survival, Subgroup 1 Analysis(from start of treatment until death within study's actual observation time for OS (22 months))
- 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)
- 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)
- Overall Survival(from start of treatment until death within study's actual observation time for OS (22 months).)
- Overall Survival, Subgroup 2 Analysis(from start of treatment until death within study's actual observation time for OS (22 months))
- 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)