Propranolol in Angiosarcoma
Primary Purpose
Angiosarcoma
Status
Active
Phase
Phase 2
Locations
Netherlands
Study Type
Interventional
Intervention
Propranolol
Sponsored by
About this trial
This is an interventional treatment trial for Angiosarcoma focused on measuring Propranolol, Angiosarcoma
Eligibility Criteria
Inclusion Criteria:
- Histological proof of angiosarcoma
- Patients with primary, recurrent and metastasised disease are eligible;
- Patients with a window of at least 3 weeks before surgery or systemic therapy;
- Age ≥ 18 years;
- Able and willing to give written informed consent;
- WHO performance status of 0, 1 or 2;
- Evaluable disease according to RECIST 1.1 criteria; radiologic visible disease is not obligated in patients with cutaneous angiosarcoma
- Minimal acceptable safety laboratory values
- ANC of ≥ 1.5 x 109 /L
- Platelet count of ≥ 100 x 109 /L
- Hepatic function as defined by serum bilirubin ≤ 1.5 x ULN, ASAT and ALAT ≤ 2.5 x ULN
- Renal function as defined by serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min (by Cockcroft-Gault formula);
- At least one tumor lesion accessible to safely biopsy per clinical judgement of the treating physician
Exclusion Criteria:
- Contraindication for propranolol therapy, like severe hypotension or bradycardia, sicksinus syndrome, second or third grade heart block, cardiogenic shock, untreated heart failure, severe peripheral vascular disease asthma or other obstructive lung diseases, untreated pheochromocytoma, metabolic acidosis, prolonged fasting.
- Current treatment with β-blockade therapy.
- Any anticancer treatment within 30 days prior to receiving the first dose of investigational treatment; with the exception of hormonal therapy for breast cancer.
- Concurrent treatment with an anticancer therapy: with the exception of hormonal therapy for breast cancer.
- Patients with known alcoholism, drug addiction and/or psychiatric of physiological condition which in the opinion of the investigator would impair study compliance;
- Evidence of any other disease, neurological or metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment-related complications;
- Pregnancy;
- Legal incapacity
Sites / Locations
- Netherlands Cancer Institute - Antoni van Leeuwenhoek
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Propranolol
Arm Description
Outcomes
Primary Outcome Measures
Clinical response
A response is defined as CR, PR, or SD with an improvement in clinical characteristics
Secondary Outcome Measures
Histological response on propranolol treatment
The histologic response defined as a decrease of >30% of Ki-67 index between pre- and post-propranolol treatment biopsies.
Full Information
NCT ID
NCT04518124
First Posted
June 9, 2020
Last Updated
August 31, 2023
Sponsor
The Netherlands Cancer Institute
Collaborators
Anticancer Fund, Belgium
1. Study Identification
Unique Protocol Identification Number
NCT04518124
Brief Title
Propranolol in Angiosarcoma
Official Title
Neoadjuvant Trial on the Efficacy of Propranolol Monotherapy in Cutaneous Angiosarcoma
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 27, 2019 (Actual)
Primary Completion Date
October 27, 2023 (Anticipated)
Study Completion Date
October 27, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The Netherlands Cancer Institute
Collaborators
Anticancer Fund, Belgium
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a window opportunity study of propranolol in patients with angiosarcoma. The aim of this study is to prospectively evaluate the activity of propranolol in the clinical setting as monotherapy, where the neoadjuvant setting provides a good opportunity to rapidly evaluate both the clinical response and histological response, without a significant delay in anti-cancer treatment.
Detailed Description
A pilot neoadjuvant window of opportunity study will be performed to explore the activity of propranolol monotherapy in angiosarcoma. The study consists of a single arm. Propranolol will be administred as monotherapy in a dose of 40-80 mg 2-3 times a day, if tolerated. When patients are diagnosed, standard anti-cancer treatment will be scheduled in 6 weeks while propranolol treatment can start immediately after diagnosis and will be continued until the day the standard anti-cancer treatment is started. The duration of treatment will therefore be 3-6 weeks.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Angiosarcoma
Keywords
Propranolol, Angiosarcoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
14 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Propranolol
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Propranolol
Intervention Description
Propranolol will be administered as monotherapy in a dose of 40-80 mg 2-3 times a day, if tolerated. The study consists of a single arm.
Primary Outcome Measure Information:
Title
Clinical response
Description
A response is defined as CR, PR, or SD with an improvement in clinical characteristics
Time Frame
From start to end of treatment: 3-6 weeks
Secondary Outcome Measure Information:
Title
Histological response on propranolol treatment
Description
The histologic response defined as a decrease of >30% of Ki-67 index between pre- and post-propranolol treatment biopsies.
Time Frame
through study completion, an average of 2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histological proof of angiosarcoma
Patients with primary, recurrent and metastasised disease are eligible;
Patients with a window of at least 3 weeks before surgery or systemic therapy;
Age ≥ 18 years;
Able and willing to give written informed consent;
WHO performance status of 0, 1 or 2;
Evaluable disease according to RECIST 1.1 criteria; radiologic visible disease is not obligated in patients with cutaneous angiosarcoma
Minimal acceptable safety laboratory values
ANC of ≥ 1.5 x 109 /L
Platelet count of ≥ 100 x 109 /L
Hepatic function as defined by serum bilirubin ≤ 1.5 x ULN, ASAT and ALAT ≤ 2.5 x ULN
Renal function as defined by serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min (by Cockcroft-Gault formula);
At least one tumor lesion accessible to safely biopsy per clinical judgement of the treating physician
Exclusion Criteria:
Contraindication for propranolol therapy, like severe hypotension or bradycardia, sicksinus syndrome, second or third grade heart block, cardiogenic shock, untreated heart failure, severe peripheral vascular disease asthma or other obstructive lung diseases, untreated pheochromocytoma, metabolic acidosis, prolonged fasting.
Current treatment with β-blockade therapy.
Any anticancer treatment within 30 days prior to receiving the first dose of investigational treatment; with the exception of hormonal therapy for breast cancer.
Concurrent treatment with an anticancer therapy: with the exception of hormonal therapy for breast cancer.
Patients with known alcoholism, drug addiction and/or psychiatric of physiological condition which in the opinion of the investigator would impair study compliance;
Evidence of any other disease, neurological or metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment-related complications;
Pregnancy;
Legal incapacity
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Winan van Houdt, MD PhD
Organizational Affiliation
Netherlands Cancer Institute - Antoni van Leeuwenhoek
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Neeltje Steeghs, MD PhD
Organizational Affiliation
Netherlands Cancer Institute - Antoni van Leeuwenhoek
Official's Role
Principal Investigator
Facility Information:
Facility Name
Netherlands Cancer Institute - Antoni van Leeuwenhoek
City
Amsterdam
Country
Netherlands
12. IPD Sharing Statement
Learn more about this trial
Propranolol in Angiosarcoma
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