Eribulin in Advanced Solitary Fibrous Tumor

Solitary Fibrous Tumor Clinical Trial

— ERASING  

Official title:

ERibulin in Advanced Solitary Fibrous Tumor, an ItaliaN Sarcoma Group Phase II Study (ERASING)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03840772
• Other study ID #: ISG-ERASING
• Status: Recruiting
• Phase: Phase 2
• Start date: July 17, 2019
• Est. completion date: April 2024

Study information

• Verified date: September 2023
• Source: Italian Sarcoma Group
• Contact: Silvia Stacchiotti, MD
• Phone: 0039022390
• Email: silvia.stacchiotti[@]istitutotumori.mi.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Phase II study on advanced Solitary Fibrous Tumor (SFT) treated with eribulin

Description:

This is an Italian, non randomized, open label, multi center, investigator-initiated, Phase II, clinical study to explore the activity of eribulin in a population of patients with progressive, advanced (i.e. locally advanced or metastatic), molecularly proven SFT. Patients with a documented and centrally reviewed pathological diagnosis of locally advanced or metastatic SFT, and with an evidence of progression within the previous 6 months, may enter the study.

Study treatments will be administered till progression or toxicity. The primary end-point of the study is overall response rate Secondary end-points are Progression Free Survival (PFS), Overall Survival (OS) clinical benefit rate, response rate as by Choi criteria, duration of response.

Subjects already treated with one or two prior medical therapy regimens for the advanced phase, whatever agent used in first- or second-line, are eligible for inclusion in the study. Investigators will consider eligible for this study even patients naïve from chemotherapy, considering the limited activity of anthracycline in the disease.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 16
• Est. completion date: April 2024
• Est. primary completion date: April 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. The patient or legal representative must be able to read and understand the informed consent form and must have been willing to give written informed consent and any locally required authorization before any study-specific procedures, including screening evaluations, sampling, and analyses

2. Age =18 years

3. Histological centrally and molecular confirmed diagnosis SFT

4. Locally advanced disease and/or metastatic disease

5. Measurable disease according RECIST 1.1

6. Evidence of progression by RECIST 1.1 during the 6 months before study entry

7. Patients must be treated with at least one prior medical anticancer treatment line for the advanced phase of disease (both cytotoxic chemotherapy or target treatment allowed) and with a maximum of 2 lines.

8. Eastern Cooperative Oncology Group (ECOG) Performance Status = 2

9. Adequate bone marrow function

10. Adequate organ function

11. Cardiac ejection fraction =50%

12. Female patients of child-bearing potential must have negative pregnancy test within 7 days before initiation each cycle of chemotherapy. Post-menopausal women must be amenorrhoeic for at least 12 months to be considered of non-childbearing potential. Male and female patients of reproductive potential must agree to employ an effective method of birth control throughout the study.

Exclusion Criteria:

1. Naïve patients

2. More than 2 lines of anticancer treatment

3. Previous treatment with any other anti-cancer investigational or not investigational agents within 21 days of first day of study drug dosing,

4. Previous treatment with radiation therapy within 14 days of first day of study drug dosing, or patients who have not recovered from adverse events due to agents previously administered

5. Previous radiotherapy to 25% of the bone marrow

6. Major surgery within 21 days prior to study entry

7. Other primary malignancy with <5 years clinically assessed disease-free interval, except basal cell skin cancer, cervical carcinoma in situ, or other neoplasms judged to entail a low risk of relapse

8. Pregnancy or breast feeding

9. Cardiovascular diseases resulting in a New York Heart Association Functional Status >2 . Medical history of a myocardial infarction < 6 months prior to initiation of study treatment. Unstable angina or myocardial infarction within 6 months of enrolment, Serious and potentially life-threatening arrhythmia

10. Subjects with a high probability of Long QT Syndrome or corrected QT interval prolongation of more than or equal to 501 msec , following correction of any electrolyte imbalance

11. Medical history of arterial thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), or pulmonary embolism within 6 months prior to the initiation of study treatment

12. Known history of human immunodeficiency virus infection

13. Active or chronic hepatitis B or C requiring treatment with antiviral therapy

14. Medical history of hemorrhage or a bleeding event = Grade 3 according Common Terminology Criteria for Adverse Events (CTCAE) within 4 weeks prior to the initiation of study treatment

15. Evidence of any other serious or unstable illness, or medical, psychological, or social condition, that could jeopardize the safety of the subject and/or his/her compliance with study procedures, or may interfere with the subject's participation in the study or evaluation of the study results

16. Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation of the study drugs

17. Subjects who have not recovered from acute toxicities as a result of prior anti-cancer therapy to = Grade 1 of CTCAE, except for peripheral neuropathy and alopecia.

18. Pre-existing peripheral neuropathy > CTCAE Grade 2.

19. Expected non-compliance to medical regimens

20. Subjects with known central nervous system metastases

Related Conditions & MeSH terms

• Hemangiopericytoma
• Solitary Fibrous Tumor
• Solitary Fibrous Tumors

Intervention

Drug:
• Eribulin
Treatment with eribulin

Locations

Country	Name	City	State
Italy	Fondazione IRCCS INT Milano	Milano
Italy	Azienda Ospedaliera Universitaria Paolo Giaccone	Palermo	PA
Italy	Policlinico Universitario Campus Biomedico	Roma	RM

Sponsors (2)

Lead Sponsor	Collaborator
Italian Sarcoma Group	Eisai Inc.

Country where clinical trial is conducted

Italy, 

References & Publications (11)

Beadle GF, Hillcoat BL. Treatment of advanced malignant hemangiopericytoma with combination adriamycin and DTIC: a report of four cases. J Surg Oncol. 1983 Mar;22(3):167-70. doi: 10.1002/jso.2930220306. — View Citation

Chamberlain MC, Glantz MJ. Sequential salvage chemotherapy for recurrent intracranial hemangiopericytoma. Neurosurgery. 2008 Oct;63(4):720-6; author reply 726-7. doi: 10.1227/01.NEU.0000325494.69836.51. — View Citation

Dagrada GP, Spagnuolo RD, Mauro V, Tamborini E, Cesana L, Gronchi A, Stacchiotti S, Pierotti MA, Negri T, Pilotti S. Solitary fibrous tumors: loss of chimeric protein expression and genomic instability mark dedifferentiation. Mod Pathol. 2015 Aug;28(8):1074-83. doi: 10.1038/modpathol.2015.70. Epub 2015 May 29. — View Citation

Galanis E, Buckner JC, Scheithauer BW, Kimmel DW, Schomberg PJ, Piepgras DG. Management of recurrent meningeal hemangiopericytoma. Cancer. 1998 May 15;82(10):1915-20. — View Citation

Kawai A, Araki N, Naito Y, Ozaki T, Sugiura H, Yazawa Y, Morioka H, Matsumine A, Saito K, Asami S, Isu K. Phase 2 study of eribulin in patients with previously treated advanced or metastatic soft tissue sarcoma. Jpn J Clin Oncol. 2017 Feb 1;47(2):137-144. doi: 10.1093/jjco/hyw175. — View Citation

Robinson DR, Wu YM, Kalyana-Sundaram S, Cao X, Lonigro RJ, Sung YS, Chen CL, Zhang L, Wang R, Su F, Iyer MK, Roychowdhury S, Siddiqui J, Pienta KJ, Kunju LP, Talpaz M, Mosquera JM, Singer S, Schuetze SM, Antonescu CR, Chinnaiyan AM. Identification of recurrent NAB2-STAT6 gene fusions in solitary fibrous tumor by integrative sequencing. Nat Genet. 2013 Feb;45(2):180-5. doi: 10.1038/ng.2509. Epub 2013 Jan 13. — View Citation

Schoffski P, Chawla S, Maki RG, Italiano A, Gelderblom H, Choy E, Grignani G, Camargo V, Bauer S, Rha SY, Blay JY, Hohenberger P, D'Adamo D, Guo M, Chmielowski B, Le Cesne A, Demetri GD, Patel SR. Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomised, open-label, multicentre, phase 3 trial. Lancet. 2016 Apr 16;387(10028):1629-37. doi: 10.1016/S0140-6736(15)01283-0. Epub 2016 Feb 10. — View Citation

Schoffski P, Ray-Coquard IL, Cioffi A, Bui NB, Bauer S, Hartmann JT, Krarup-Hansen A, Grunwald V, Sciot R, Dumez H, Blay JY, Le Cesne A, Wanders J, Hayward C, Marreaud S, Ouali M, Hohenberger P; European Organisation for Research and Treatment of Cancer (EORTC) Soft Tissue and Bone Sarcoma Group (STBSG). Activity of eribulin mesylate in patients with soft-tissue sarcoma: a phase 2 study in four independent histological subtypes. Lancet Oncol. 2011 Oct;12(11):1045-52. doi: 10.1016/S1470-2045(11)70230-3. Epub 2011 Sep 19. Erratum In: Lancet Oncol. 2015 Sep;16(9):e427. — View Citation

Stacchiotti S, Libertini M, Negri T, Palassini E, Gronchi A, Fatigoni S, Poletti P, Vincenzi B, Dei Tos AP, Mariani L, Pilotti S, Casali PG. Response to chemotherapy of solitary fibrous tumour: a retrospective study. Eur J Cancer. 2013 Jul;49(10):2376-83. doi: 10.1016/j.ejca.2013.03.017. Epub 2013 Apr 6. — View Citation

Van Glabbeke M, Verweij J, Judson I, Nielsen OS; EORTC Soft Tissue and Bone Sarcoma Group. Progression-free rate as the principal end-point for phase II trials in soft-tissue sarcomas. Eur J Cancer. 2002 Mar;38(4):543-9. doi: 10.1016/s0959-8049(01)00398-7. — View Citation

Verbeke SL, Fletcher CD, Alberghini M, Daugaard S, Flanagan AM, Parratt T, Kroon HM, Hogendoorn PC, Bovee JV. A reappraisal of hemangiopericytoma of bone; analysis of cases reclassified as synovial sarcoma and solitary fibrous tumor of bone. Am J Surg Pathol. 2010 Jun;34(6):777-83. doi: 10.1097/PAS.0b013e3181dbedf1. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	RECIST 1.1 Overall response rate	Proportion of patients with tumor size reduction ? to 30% measured with RECIST Criteria 1.1	At week 6
Secondary	Choi Response Rate	Proportion of patients with tumor size reduction ?10% or a decrease in tumour attenuation?15% measured with Choi criteria	At week 6
Secondary	Overall Survival (OS) at 3 years	Survival from the first eribulin dose to death for any cause	At 3 years
Secondary	Progression Free Survival (PFS) at 3 years	Survival without disease progression	At 3 years
Secondary	Clinical Benefit Rate	Proportion of patients with no disease progression after 18 weeks of therapy.	At week 18
Secondary	Safety of the treatment in term of adverse event	Safety in term of adverse event is evaluate from the first eribulin dose throughout the study according to CTCAE 5.0	Week 9, week 18, week 27, week 36