A Study Investigating SGI-110 in Combination With Ipilimumab in Unresectable or Metastatic Melanoma Patients
NCT ID: NCT02608437
Last Updated: 2015-11-18
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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UNKNOWN
PHASE1
19 participants
INTERVENTIONAL
2015-10-31
2018-10-31
Brief Summary
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Detailed Description
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Targeting immune check-point(s) with immunomodulatory monoclonal antibody (mAb) is a novel and rapidly evolving strategy to treat cancer, that is rapidly spreading to different tumor histologies. The prototype approach of this therapeutic modality relies on the inhibition of negative signals delivered by CTLA-4 expressed on T lymphocytes. CTLA-4 blockade has profoundly changed the therapeutic landscape of metastatic melanoma (MM), significantly improving the survival of MM patients; however, objective clinical responses are limited, and only a minority of patients achieves long-term disease control.1 Therefore, several combination approaches are being explored to improve the efficacy of CTLA-4 blockade. Along this line, based on the preclinical evidence the investigators gained on the broad immunomodulatory activity of SGI-110, the exploratory phase 1 combination study NIBIT-M4 has been designed to provide proof-of-concept evidence to the immunologic and clinical efficacy of CTLA-4 blockade combined with DNA-HypomethylatingAgent (DHA). Progressing Stage III or Stage IV MM patients, amenable to serial tumor biopsies will be enrolled in the study.
Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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SGI-110 and Ipilimumab
SGI-110 in combination with Ipilimumab
SGI-110
SGI-110: start at 30 mg/m2 s.c. on W0, 3, 6, 9 Day 1 - 5 q21 days. Dose level -1: 15 mg/m2; dose level +1: 45 mg/m2
Ipilimumab
ipilimumab: 3 mg/Kg i.v. over 90 minutes on W1, 4, 7 and 10 for a total of 4 cycles.
Interventions
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SGI-110
SGI-110: start at 30 mg/m2 s.c. on W0, 3, 6, 9 Day 1 - 5 q21 days. Dose level -1: 15 mg/m2; dose level +1: 45 mg/m2
Ipilimumab
ipilimumab: 3 mg/Kg i.v. over 90 minutes on W1, 4, 7 and 10 for a total of 4 cycles.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Unresectable Stage III or Stage IV melanoma with measurable lesions by CT or MRI per mWHO/irRC criteria, that can be amenable to biopsy
* Previously treated or untreated; prior therapy may include chemotherapy or targeted therapy for metastatic disease (i.e., BRAF and/or MAP-ERK kinase (MEK) inhibitor). Prior adjuvant interferon is permitted
* Subjects with Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
* 4 weeks or greater since last treatment
* Must have recovered from any acute toxicity associated with prior therapy
* Life expectancy greater than 16 weeks
* Negative screening tests for HIV, Hepatitis B, and Hepatitis C
* Women of child-bearing potential must not be pregnant or breastfeeding, must have a negative pregnancy test at Screening and all men must be practicing two medically acceptable methods of birth control. Men should not father a child while receiving treatment with SGI-110 + ipilimumab, and for 2 months following completion of treatment. Men with female partners of childbearing potential should use effective contraception during this time
Exclusion Criteria
* Subjects with active brain metastases or leptomeningeal metastases
* Subjects with metastatic uveal melanoma
* Subjects with active, known or suspected autoimmune disease
* Subjects with a condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of treatment
* Subjects with symptomatic effusions on account of pleural, pericardial metastases of melanoma
* Prior treatment with an anti-Programmed Death receptor-1 (PD-1), anti-Programmed Death-1 ligand-1 (PD-L1), anti-PD-L2, or anti-CTLA-4 antibody
* Subjects who had major surgery or radiation therapy within 21 days of starting treatment
* Subjects who are unable to return for follow-up visits as required by this study
* Prisoners or subjects who are involuntarily incarcerated
* Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness.
18 Years
ALL
No
Sponsors
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Astex Pharmaceuticals, Inc.
INDUSTRY
Italian Network for Tumor Biotherapy Foundation
OTHER
Responsible Party
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Principal Investigators
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Anna Maria Di Giacomo, PhD,MD
Role: PRINCIPAL_INVESTIGATOR
Medical Oncology and Immunotherapy Unit, University Hospital of Siena
Locations
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Medical Oncology and Immunotherapy Unit, University Hospital of Siena
Siena, , Italy
Countries
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Central Contacts
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Facility Contacts
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References
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Maio M, Di Giacomo AM, Robert C, Eggermont AM. Update on the role of ipilimumab in melanoma and first data on new combination therapies. Curr Opin Oncol. 2013 Mar;25(2):166-72. doi: 10.1097/CCO.0b013e32835dae4f.
Covre A, Coral S, Di Giacomo AM, Taverna P, Azab M, Maio M. Epigenetics meets immune checkpoints. Semin Oncol. 2015 Jun;42(3):506-13. doi: 10.1053/j.seminoncol.2015.02.003. Epub 2015 Feb 14.
Kantarjian H, Oki Y, Garcia-Manero G, Huang X, O'Brien S, Cortes J, Faderl S, Bueso-Ramos C, Ravandi F, Estrov Z, Ferrajoli A, Wierda W, Shan J, Davis J, Giles F, Saba HI, Issa JP. Results of a randomized study of 3 schedules of low-dose decitabine in higher-risk myelodysplastic syndrome and chronic myelomonocytic leukemia. Blood. 2007 Jan 1;109(1):52-7. doi: 10.1182/blood-2006-05-021162. Epub 2006 Aug 1.
Noviello TMR, Di Giacomo AM, Caruso FP, Covre A, Mortarini R, Scala G, Costa MC, Coral S, Fridman WH, Sautes-Fridman C, Brich S, Pruneri G, Simonetti E, Lofiego MF, Tufano R, Bedognetti D, Anichini A, Maio M, Ceccarelli M. Guadecitabine plus ipilimumab in unresectable melanoma: five-year follow-up and integrated multi-omic analysis in the phase 1b NIBIT-M4 trial. Nat Commun. 2023 Sep 22;14(1):5914. doi: 10.1038/s41467-023-40994-4.
Amaro A, Reggiani F, Fenoglio D, Gangemi R, Tosi A, Parodi A, Banelli B, Rigo V, Mastracci L, Grillo F, Cereghetti A, Tastanova A, Ghosh A, Sallustio F, Emionite L, Daga A, Altosole T, Filaci G, Rosato A, Levesque M, Maio M, Pfeffer U, Croce M; EPigenetic Immune-oncology Consortium Airc (EPICA) consortium. Guadecitabine increases response to combined anti-CTLA-4 and anti-PD-1 treatment in mouse melanoma in vivo by controlling T-cells, myeloid derived suppressor and NK cells. J Exp Clin Cancer Res. 2023 Mar 18;42(1):67. doi: 10.1186/s13046-023-02628-x.
Related Links
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Fondazione NIBIT
Other Identifiers
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NIBIT-M4
Identifier Type: -
Identifier Source: org_study_id