A Study Investigating SGI-110 in Combination With Ipilimumab in Unresectable or Metastatic Melanoma Patients
NIBIT-M4
A Phase 1b, Open-label, Dose Escalation Study Investigating Different Doses of SGI-110 in Combination With Ipilimumab in Unresectable or Metastatic Melanoma Patients
1 other identifier
interventional
19
1 country
1
Brief Summary
Thi pahse I, dose-escalation trial will determine the MTD, safety and the additional benefit achieved from adding SGI-110 to ipilimumab therapy in metastatic melanoma patients. Preclinical evidence generated with SGI-110 in vivo demonstrated that besides having a direct activity on tumor growth as a single agent, SGI-110 was able to "sensitize" neoplastic cells to the anti-tumor activity of CTLA-4 blockade, providing a sound scientific rationale to develop new immunotherapeutic approaches combining SGI-110 with therapeutic mAb to immune check-points.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Oct 2015
Typical duration for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
October 1, 2015
CompletedFirst Submitted
Initial submission to the registry
November 13, 2015
CompletedFirst Posted
Study publicly available on registry
November 18, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
October 1, 2018
CompletedNovember 18, 2015
November 1, 2015
1 year
November 13, 2015
November 16, 2015
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Maximum Tolerated Dose (MTD) of SGI-110 in combination with ipilimumab
The primary objective is to determine the MTD of SGI-110 in combination with ipilimumab in 21 day cycles in melanoma patients. Endpoints related to this objective include an evaluation of Dose Limiting Toxicity(s). The MTD evaluation will be based on the DLT evaluable population.
the first 3 weeks of treatment
Secondary Outcomes (5)
Immune-related Disease Control Rate (irDCR)
weeks 24
Immune-related Objective Response Rate (irORR)
weeks 24
Immune-related Time to Response (irTTR)
weeks 24
Immune-related Duration of Response (irDoR)
2 years
Immune-related progression free survival (irPFS)
2 years
Other Outcomes (3)
Phenotypic/epigenetic profile of tumor samples and peripheral blood mononuclear cells
2 years
humoral immune responses induced by treatment
2 years
Maximum Plasma Concentration [Cmax] of of SGI-110 and decitabine.
24 hours
Study Arms (1)
SGI-110 and Ipilimumab
EXPERIMENTALSGI-110 in combination with Ipilimumab
Interventions
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: 3 mg/Kg i.v. over 90 minutes on W1, 4, 7 and 10 for a total of 4 cycles.
Eligibility Criteria
You may qualify if:
- Willing and able to give written informed consent
- 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
- 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
You may not qualify if:
- Subjects with any contraindications for ipilimumab
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Medical Oncology and Immunotherapy Unit, University Hospital of Siena
Siena, 53100, Italy
Related Publications (5)
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.
PMID: 23299197BACKGROUNDCovre 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.
PMID: 25965370BACKGROUNDKantarjian 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.
PMID: 16882708RESULTNoviello 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.
PMID: 37739939DERIVEDAmaro 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.
PMID: 36934257DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Anna Maria Di Giacomo, PhD,MD
Medical Oncology and Immunotherapy Unit, University Hospital of Siena
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 13, 2015
First Posted
November 18, 2015
Study Start
October 1, 2015
Primary Completion
October 1, 2016
Study Completion
October 1, 2018
Last Updated
November 18, 2015
Record last verified: 2015-11