Eribulin in Angiosarcoma and Epithelioid Hemangioendothelioma (EHE)
Primary Purpose
Angiosarcoma, Epithelioid Hemangioendothelioma
Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Eribulin
Sponsored by
About this trial
This is an interventional treatment trial for Angiosarcoma focused on measuring Epithelioid hemangioendothelioma (EHE), Angiosarcoma
Eligibility Criteria
Inclusion Criteria:
- Metastatic or locally advanced angiosarcoma, treated with at least one prior systemic therapy where no standard of care curable therapy is available OR metastatic or locally advanced malignant and progressive epithelioid hemangioendothelioma (EHE).
- A maximum of 5 EHE patients will be accrued on this study
- Archival tissue confirming the diagnosis must be reviewed by BWH/DFCI/MGH pathology.
- Progression on at least one prior systemic therapy or progression during an observation phase of no anti-cancer therapy within the prior 3 months; prior taxanes are allowed
- Participants must have measurable disease by RECIST 1.1, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm with conventional techniques or as ≥10 mm with spiral CT scan, MRI, or calipers by clinical exam.
- Age > 18 years.
- ECOG performance status ≤2
- Life expectancy of greater than 3 months
Participants must have normal organ and marrow function as defined below:
- leukocytes ≥3,000/mcL
- absolute neutrophil count ≥1,000/mcL
- platelets ≥100,000/mcL
- total bilirubin within normal institutional limits
- AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal
- creatinine clearance ≥50 mL/min/1.73 m2 for participants with creatinine levels above institutional normal.
- Baseline QTcF < grade 2
- The effects of Eribulin on the developing human fetus are unknown. For this reason and because of the risk of teratogenicity, women of child-bearing potential must agree to use adequate contraception prior to study entry and for the duration of study participation, and 4 months after completion of Eribulin administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of Eribulin administration.
- Willingness to undergo serial tumor biopsies before and on treatment.
- Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
- Participants who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C), immunotherapy within 3 weeks, targeted therapies (e.g. small molecule inhibitors such as pazopanib) within 2 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. Not clinically significant or clinically stable adverse events from prior therapy (e.g. immunotherapy related hypothyroidism or insulin-dependent diabetes stable on medication or TKI-related hypertension or rash etc.) is allowed.
- Participants who are receiving any other investigational agents.
- Participants with known brain metastases and/or leptomeningeal disease should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to eribulin.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (NYHA Class II), unstable angina pectoris or myocardial infarction within 6 months of enrolment, serious or life-threatening cardiac arrhythmia, subjects with a high probability of Long QT syndrome or QTcF prolongation of > 501 mcsec (grade 2) on at least two separate ECG following correction of any electrolyte imbalance or psychiatric illness/social situations that would limit compliance with study requirements.
- Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta-human chorionic gonadotropin [ß-hCG] (or human chorionic gonadotropin [hCG]) test with a minimum sensitivity of 25 IU/L or equivalent units of ß-hCG [or hCG]). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug.
- HIV-positive participants on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with Eribulin. In addition, these participants are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated
Sites / Locations
- Massachusetts General Hospital
- Dana Farber Cancer Institute
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Eribulin
Arm Description
Eribulin administered twice per cycle intravenously Each cycle contains 21 days Dosing is per the FDA label for other cancers
Outcomes
Primary Outcome Measures
Objective Response Rate
Partial response rate plus complete response rate by RECIST 1.1
Secondary Outcome Measures
Progression Free Survival
Disease Control Rate
Objective Response plus Stable Disease Rate at 24 weeks
Treatment Related Adverse Events
Summary of the treatment related adverse events experienced by study participants as assessed by Common Terminology Criteria for Adverse Events (CTCAE v4)
Full Information
NCT ID
NCT03331250
First Posted
October 26, 2017
Last Updated
March 16, 2023
Sponsor
Massachusetts General Hospital
Collaborators
Eisai Inc.
1. Study Identification
Unique Protocol Identification Number
NCT03331250
Brief Title
Eribulin in Angiosarcoma and Epithelioid Hemangioendothelioma (EHE)
Official Title
A Pilot Phase 2 Study of Eribulin in Angiosarcoma and Epithelioid Hemangioendothelioma (EHE)
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 18, 2018 (Actual)
Primary Completion Date
July 21, 2022 (Actual)
Study Completion Date
May 31, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital
Collaborators
Eisai Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This research study is studying a drug as a possible treatment for Angiosarcoma or Epithelioid hemangioendothelioma (EHE).
-The drug involved in this study is Eribulin
Detailed Description
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied.
The FDA (the U.S. Food and Drug Administration) has not approved Eribulin for your specific disease but it has been approved for other uses.
In this research study, the investigators are studying how safe and effective eribulin is in participants with Angiosarcoma or EHE.
Eribulin was created to mimic the structure of a chemical that is released from a sea sponge. The investigators believe that this drug has anti-cancer effects on tumors by blocking proteins called microtubules, among other functions. It may work by preventing the cancer cells from dividing and eventually cause the tumor cells to die similar to other drugs that target microtubules
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Angiosarcoma, Epithelioid Hemangioendothelioma
Keywords
Epithelioid hemangioendothelioma (EHE), 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
13 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Eribulin
Arm Type
Experimental
Arm Description
Eribulin administered twice per cycle intravenously
Each cycle contains 21 days
Dosing is per the FDA label for other cancers
Intervention Type
Drug
Intervention Name(s)
Eribulin
Other Intervention Name(s)
Halaven
Intervention Description
It may work by preventing the cancer cells from dividing and eventually cause the tumor cells to die
Primary Outcome Measure Information:
Title
Objective Response Rate
Description
Partial response rate plus complete response rate by RECIST 1.1
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Progression Free Survival
Time Frame
4 years
Title
Disease Control Rate
Description
Objective Response plus Stable Disease Rate at 24 weeks
Time Frame
24 weeks
Title
Treatment Related Adverse Events
Description
Summary of the treatment related adverse events experienced by study participants as assessed by Common Terminology Criteria for Adverse Events (CTCAE v4)
Time Frame
4 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Metastatic or locally advanced angiosarcoma, treated with at least one prior systemic therapy where no standard of care curable therapy is available OR metastatic or locally advanced malignant and progressive epithelioid hemangioendothelioma (EHE).
A maximum of 5 EHE patients will be accrued on this study
Archival tissue confirming the diagnosis must be reviewed by BWH/DFCI/MGH pathology.
Progression on at least one prior systemic therapy or progression during an observation phase of no anti-cancer therapy within the prior 3 months; prior taxanes are allowed
Participants must have measurable disease by RECIST 1.1, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm with conventional techniques or as ≥10 mm with spiral CT scan, MRI, or calipers by clinical exam.
Age > 18 years.
ECOG performance status ≤2
Life expectancy of greater than 3 months
Participants must have normal organ and marrow function as defined below:
leukocytes ≥3,000/mcL
absolute neutrophil count ≥1,000/mcL
platelets ≥100,000/mcL
total bilirubin within normal institutional limits
AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal
creatinine clearance ≥50 mL/min/1.73 m2 for participants with creatinine levels above institutional normal.
Baseline QTcF < grade 2
The effects of Eribulin on the developing human fetus are unknown. For this reason and because of the risk of teratogenicity, women of child-bearing potential must agree to use adequate contraception prior to study entry and for the duration of study participation, and 4 months after completion of Eribulin administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of Eribulin administration.
Willingness to undergo serial tumor biopsies before and on treatment.
Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
Participants who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C), immunotherapy within 3 weeks, targeted therapies (e.g. small molecule inhibitors such as pazopanib) within 2 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. Not clinically significant or clinically stable adverse events from prior therapy (e.g. immunotherapy related hypothyroidism or insulin-dependent diabetes stable on medication or TKI-related hypertension or rash etc.) is allowed.
Participants who are receiving any other investigational agents.
Participants with known brain metastases and/or leptomeningeal disease should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
History of allergic reactions attributed to compounds of similar chemical or biologic composition to eribulin.
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (NYHA Class II), unstable angina pectoris or myocardial infarction within 6 months of enrolment, serious or life-threatening cardiac arrhythmia, subjects with a high probability of Long QT syndrome or QTcF prolongation of > 501 mcsec (grade 2) on at least two separate ECG following correction of any electrolyte imbalance or psychiatric illness/social situations that would limit compliance with study requirements.
Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta-human chorionic gonadotropin [ß-hCG] (or human chorionic gonadotropin [hCG]) test with a minimum sensitivity of 25 IU/L or equivalent units of ß-hCG [or hCG]). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug.
HIV-positive participants on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with Eribulin. In addition, these participants are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gregory Cote, MD, PhD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Eribulin in Angiosarcoma and Epithelioid Hemangioendothelioma (EHE)
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