Eribulin in Angiosarcoma and Epithelioid Hemangioendothelioma (EHE)

• ClinicalTrials.gov Identifier: NCT03331250
• Recruitment Status: Active, not recruiting
• First Posted: November 6, 2017
• Last Update Posted: March 20, 2023
• Sponsor: Massachusetts General Hospital
• Collaborator: Eisai Inc.
• Information provided by (Responsible Party): Gregory Cote, Massachusetts General Hospital

Tracking Information

• First Submitted Date: October 26, 2017
• First Posted Date: November 6, 2017
• Last Update Posted Date: March 20, 2023
• Actual Study Start Date: January 18, 2018
• Actual Primary Completion Date: July 21, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 31, 2017)

Objective Response Rate [ Time Frame: 2 years ]

Partial response rate plus complete response rate by RECIST 1.1

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 31, 2017)

• Progression Free Survival [ Time Frame: 4 years ]
• Disease Control Rate [ Time Frame: 24 weeks ]
  Objective Response plus Stable Disease Rate at 24 weeks
• Treatment Related Adverse Events [ Time Frame: 4 years ]
  Summary of the treatment related adverse events experienced by study participants as assessed by Common Terminology Criteria for Adverse Events (CTCAE v4)

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Eribulin in Angiosarcoma and Epithelioid Hemangioendothelioma (EHE)
• Official Title: A Pilot Phase 2 Study of Eribulin in Angiosarcoma and Epithelioid Hemangioendothelioma (EHE)

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

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Angiosarcoma
• Epithelioid Hemangioendothelioma

Intervention

Drug: Eribulin

It may work by preventing the cancer cells from dividing and eventually cause the tumor cells to die

Other Name: Halaven

Study Arms

Experimental: Eribulin

• Eribulin administered twice per cycle intravenously
• Each cycle contains 21 days
• Dosing is per the FDA label for other cancers

Intervention: Drug: Eribulin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: March 16, 2023): 13
• Original Estimated Enrollment (submitted: October 31, 2017): 16
• Estimated Study Completion Date: May 31, 2025
• Actual Primary Completion Date: July 21, 2022 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03331250
• Other Study ID Numbers: 17-355
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Gregory Cote, Massachusetts General Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: Massachusetts General Hospital
• Original Study Sponsor: Same as current
• Collaborators: Eisai Inc.

Investigators

• Principal Investigator: Gregory Cote, MD, PhD; Massachusetts General Hospital

• PRS Account: Massachusetts General Hospital
• Verification Date: March 2023