A Study Investigating SGI-110 in Combination With Ipilimumab in Unresectable or Metastatic Melanoma Patients (NIBIT-M4)

November 16, 2015 updated by: Italian Network for Tumor Biotherapy Foundation

A Phase 1b, Open-label, Dose Escalation Study Investigating Different Doses of SGI-110 in Combination With Ipilimumab in Unresectable or Metastatic Melanoma Patients

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Epigenetic alterations play a pivotal role in cancer development and progression. Pharmacologic reversion of such alterations is feasible, and second generation "epigenetic drugs" are in development and have demonstrated to possess significant immunomodulatory properties. This knowledge, together with the availability of new and highly effective immuno-therapeutic agents including immune check-point(s) blocking monoclonal antibodies, allows us to plan for highly innovative proof-of-principle combination studies that will likely open the path to more effective anti-cancer therapies.

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.

Study Type

Interventional

Enrollment (Anticipated)

19

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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
  • 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 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

Other Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: SGI-110 and Ipilimumab
SGI-110 in combination with Ipilimumab
Drug: 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
Drug: Ipilimumab
ipilimumab: 3 mg/Kg i.v. over 90 minutes on W1, 4, 7 and 10 for a total of 4 cycles.
Other Names:
  • Ipilimumab(Yervoy)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum Tolerated Dose (MTD) of SGI-110 in combination with ipilimumab
Time Frame: the first 3 weeks of treatment
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Immune-related Disease Control Rate (irDCR)
Time Frame: weeks 24
Immune-related Disease Control Rate (irDCR) is the proportion of treated subjects with an immune-related Best Overall Responce (ir-BOR) of confirmed irCR, confirmed irPR or irSD.
weeks 24
Immune-related Objective Response Rate (irORR)
Time Frame: weeks 24
Immune-related Objective Response Rate (irORR) is the proportion of treated subjects with a irBOR of confirmed irCR or confirmed irPR.
weeks 24
Immune-related Time to Response (irTTR)
Time Frame: weeks 24
Immune-related Time to Response (irTTR) is defined as the time from first dosing date until the measurement criteria are first met for overall response of irPR or irCR (whichever status comes first, and provided it is subsequently confirmed).
weeks 24
Immune-related Duration of Response (irDoR)
Time Frame: 2 years
Immune-related Duration of Response (irDoR) for the subjects whose irBOR is irCR or irPR will be defined as the time between the date of response of confirmed irCR or confirmed irPR (whichever occurs first) and the date of irPD or death (whichever occurs first). The onset of a confirmed irCR or irPR is determined by the initial assessment of response, not by the confirmatory assessment. Note that if an assessment of irPR occurs before confirmation of irCR, the duration of immune-related response endpoint will not begin at the time that the irBOR of irCR is shown but rather at the earlier time-point showing irPR. For subjects who remain alive and have not progressed following response, irDoR will be censored on the date of last evaluable Tumor Assessment.
2 years
Immune-related progression free survival (irPFS)
Time Frame: 2 years
Immune-related progression free survival (irPFS) per irRC will be defined as the time between the date of randomization and the date of progression per irRC or death, whichever occurs first. A subject who dies without reported progression per irRC will be considered to have progressed on the date of death. For those subjects who remain alive and have not progressed, irPFS will be censored on the date of last evaluable Tumor Assesment. For those subjects who remain alive and have no recorded post baseline Tumor Assessment, irPFS will be censored on the day of last clinical evaluation.
2 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phenotypic/epigenetic profile of tumor samples and peripheral blood mononuclear cells
Time Frame: 2 years
Changes in the immune phenotype/epigenetic profile of neoplastic cells and of immune cells.
2 years
humoral immune responses induced by treatment
Time Frame: 2 years
Changes in the humoral and cellular immune responses induced by treatment will be investigated utilizing standardized and validated techniques.
2 years
Maximum Plasma Concentration [Cmax] of of SGI-110 and decitabine.
Time Frame: 24 hours
Plasma samples will be prepared from blood drawn at the following time-points: Cycle 1, Day 1: pre-dose, 15 min, 30 min, 60 min, 90 min, 2 hr, 4 hr, 6 hr and 8 hr post-dose.
24 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Italian Network for Tumor Biotherapy Foundation

Collaborators

Astex Pharmaceuticals, Inc.

Investigators

  • Principal Investigator: Anna Maria Di Giacomo, PhD,MD, Medical Oncology and Immunotherapy Unit, University Hospital of Siena

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2015

Primary Completion (Anticipated)

October 1, 2016

Study Completion (Anticipated)

October 1, 2018

Study Registration Dates

First Submitted

November 13, 2015

First Submitted That Met QC Criteria

November 16, 2015

First Posted (Estimate)

November 18, 2015

Study Record Updates

Last Update Posted (Estimate)

November 18, 2015

Last Update Submitted That Met QC Criteria

November 16, 2015

Last Verified

November 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NIBIT-M4

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Metastatic Melanoma

Clinical Trials on SGI-110

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Cyprus

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe