Avelumab in Combination With Gemcitabine in Advanced Leiomyosarcoma as a Second-line Treatment

Leiomyosarcoma Metastatic Clinical Trial

— EAGLES  

Official title:

Phase II Trial of Avelumab in Combination With Gemcitabine in Advanced Leiomyosarcoma as a Second-line Treatment

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03536780
• Other study ID #: KCSG UN18-06
• Secondary ID: MS100070_0069
• Status: Recruiting
• Phase: Phase 2
• Start date: October 1, 2018
• Est. completion date: December 31, 2022

Study information

• Verified date: February 2021
• Source: Gachon University Gil Medical Center
• Contact: Young Saing Kim, MD, PhD
• Phone: +82-032-460-3231
• Email: zoomboom[@]gilhospital.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A Phase 2 trial of avelumab plus gemcitabine in advanced leiomyosarcoma as a second line treatment

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 38
• Est. completion date: December 31, 2022
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

1. Unresectable, advanced or metastatic histologically confirmed leiomyosarcoma

2. Progression during or after first-line doxorubicin-based chemotherapy (relapse within 6 months of completion of adjuvant/neoadjuvant chemotherapy containing doxorubicin-based regimen could be considered as first-line therapy.)

3. ECOG PS 0-2

4. At least one measurable lesion according to RECIST v1.1

5. Adequate organ function

6. Life expectancy >= 3 months

7. Negative serum or urine pregnancy test at screening for women of childbearing potential

Exclusion Criteria:

1. Prior treatment history of anti-PD-1/PD-L1 or anti-CTLA4 treatment

2. Receipt of 2 or more prior systemic treatments for advanced leiomyosarcoma

3. Active or untreated brain metastases or spinal cord compression

4. Prior treatment with gemcitabine

5. History of major surgery within 4 weeks prior to enrollment

6. Chemotherapy or radiotherapy within 3 weeks prior to the study drug commencement

7. Previous malignant disease other than leiomyosarcoma within the last 5 years with the exception of basal or squamous cell carcinoma of skin or carcinoma in situ (bladder, cervical, colorectal, breast)

8. Pregnant or lactating women

9. HIV, HBV, or HCV infection

10. Severe hypersensitivity or anaphylaxis to monoclonal antibody, or uncontrolled bronchial asthma

11. Current use of immunosuppressive agent (exclusion : less than prednisone 10 mg/day or equivalent)

12. Active autoimmune disease

13. Clinically significant cardiovascular disease

14. Clinically significant interstitial pneumonitis or pulmonary fibrosis

15. Vaccination within 4 weeks of the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines

Related Conditions & MeSH terms

• Leiomyosarcoma
• Leiomyosarcoma Metastatic

Intervention

Drug:
• Avelumab and Gemcitabine
Avelumab: 10 mg/kg by IV infusion over 1 hour, every 2 weeks Gemcitabine: 1000 mg/m2 by IV infusion over 30 minutes on Days 1, 8, and 15 of each 28-day cycle

Locations

Country	Name	City	State
Korea, Republic of	Dong-a University Hospital	Busan
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul

Sponsors (3)

Lead Sponsor	Collaborator
Gachon University Gil Medical Center	Chong Kun Dang Pharmaceutical Corp., Merck KGaA, Darmstadt, Germany

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (11)

Chen G, Emens LA. Chemoimmunotherapy: reengineering tumor immunity. Cancer Immunol Immunother. 2013 Feb;62(2):203-16. doi: 10.1007/s00262-012-1388-0. Epub 2013 Feb 7. Review. — View Citation

Clark MA, Fisher C, Judson I, Thomas JM. Soft-tissue sarcomas in adults. N Engl J Med. 2005 Aug 18;353(7):701-11. Review. — View Citation

Dunn GP, Bruce AT, Ikeda H, Old LJ, Schreiber RD. Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol. 2002 Nov;3(11):991-8. Review. — View Citation

Galluzzi L, Senovilla L, Zitvogel L, Kroemer G. The secret ally: immunostimulation by anticancer drugs. Nat Rev Drug Discov. 2012 Feb 3;11(3):215-33. doi: 10.1038/nrd3626. Review. — View Citation

Hensley ML, Maki R, Venkatraman E, Geller G, Lovegren M, Aghajanian C, Sabbatini P, Tong W, Barakat R, Spriggs DR. Gemcitabine and docetaxel in patients with unresectable leiomyosarcoma: results of a phase II trial. J Clin Oncol. 2002 Jun 15;20(12):2824-31. — View Citation

Kelly K, Infante JR, Taylor MH, Patel MR, Wong DJ, Iannotti N, Mehnert JM, Loos AH, Koch H, Speit I, Gulley JL. Safety profile of avelumab in patients with advanced solid tumors: A pooled analysis of data from the phase 1 JAVELIN solid tumor and phase 2 JAVELIN Merkel 200 clinical trials. Cancer. 2018 May 1;124(9):2010-2017. doi: 10.1002/cncr.31293. Epub 2018 Feb 22. — View Citation

Kim JM, Chen DS. Immune escape to PD-L1/PD-1 blockade: seven steps to success (or failure). Ann Oncol. 2016 Aug;27(8):1492-504. doi: 10.1093/annonc/mdw217. Epub 2016 May 20. Review. — View Citation

Linch M, Miah AB, Thway K, Judson IR, Benson C. Systemic treatment of soft-tissue sarcoma-gold standard and novel therapies. Nat Rev Clin Oncol. 2014 Apr;11(4):187-202. doi: 10.1038/nrclinonc.2014.26. Epub 2014 Mar 18. Review. — View Citation

Pautier P, Floquet A, Penel N, Piperno-Neumann S, Isambert N, Rey A, Bompas E, Cioffi A, Delcambre C, Cupissol D, Collin F, Blay JY, Jimenez M, Duffaud F. Randomized multicenter and stratified phase II study of gemcitabine alone versus gemcitabine and docetaxel in patients with metastatic or relapsed leiomyosarcomas: a Federation Nationale des Centres de Lutte Contre le Cancer (FNCLCC) French Sarcoma Group Study (TAXOGEM study). Oncologist. 2012;17(9):1213-20. Epub 2012 Aug 20. — View Citation

Seddon B, Strauss SJ, Whelan J, Leahy M, Woll PJ, Cowie F, Rothermundt C, Wood Z, Benson C, Ali N, Marples M, Veal GJ, Jamieson D, Küver K, Tirabosco R, Forsyth S, Nash S, Dehbi HM, Beare S. Gemcitabine and docetaxel versus doxorubicin as first-line treatment in previously untreated advanced unresectable or metastatic soft-tissue sarcomas (GeDDiS): a randomised controlled phase 3 trial. Lancet Oncol. 2017 Oct;18(10):1397-1410. doi: 10.1016/S1470-2045(17)30622-8. Epub 2017 Sep 4. — View Citation

Tawbi HA, Burgess M, Bolejack V, Van Tine BA, Schuetze SM, Hu J, D'Angelo S, Attia S, Riedel RF, Priebat DA, Movva S, Davis LE, Okuno SH, Reed DR, Crowley J, Butterfield LH, Salazar R, Rodriguez-Canales J, Lazar AJ, Wistuba II, Baker LH, Maki RG, Reinke D, Patel S. Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): a multicentre, two-cohort, single-arm, open-label, phase 2 trial. Lancet Oncol. 2017 Nov;18(11):1493-1501. doi: 10.1016/S1470-2045(17)30624-1. Epub 2017 Oct 4. Erratum in: Lancet Oncol. 2017 Dec;18(12 ):e711. Erratum in: Lancet Oncol. 2018 Jan;19(1):e8. — View Citation

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate	response rate according to RECIST v1.1	3 years