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Trial record 26 of 42 for:    Malignant Hyperthermia 5

Tinostamustine and Nivolumab in Advanced Melanoma (ENIgMA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03903458
Recruitment Status : Recruiting
First Posted : April 4, 2019
Last Update Posted : April 8, 2019
Information provided by (Responsible Party):
Markus Joerger, Cantonal Hospital of St. Gallen

Brief Summary:
This trial is a first-in-human drug combination with the first-in-class alkylating histone deacetylase inhibition (HDACi) fusion molecule Tinostamustine (EDO-S101) and the anti-PD-1 monoclonal antibody Nivolumab in patients with refractory, locally advanced or metastatic melanoma.

Condition or disease Intervention/treatment Phase
Malignant Melanoma Drug: Tinostamustine Phase 1

Detailed Description:
Despite improvement of systemic treatment in patients with advanced melanoma, there is still unmet medical need in this group of patients. Tinostamustine is a medication without marketing authorization, while Nivolumab is approved for several tumor entities. The primary objective of this trial is to assesses the safety, tolerability and recommended dose of Tinostamustine in combination with Nivolumab in patients with advanced melanoma.Secondary objectives of this trial in patients with advanced solid tumors are to assess the preliminary efficacy of Tinostamustine when given in combination with Nivolumab and to characterize potential predictive biomarkers of the combination treatment of Tinostamustine and Nivolumab. The trial includeds patients with either histologically or cytologically confirmed inoperable stage III or metastatic stage IV melanoma with an indication for the regular systemic treatment with Nivolumab and a maximum of 1 prior systemic palliative line of treatment.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 21 participants
Intervention Model: Single Group Assignment
Intervention Model Description: this is an open label, non-randomized, Phase IB clinical trial studying a new anticancer drug combination
Masking: None (Open Label)
Masking Description: open-label
Primary Purpose: Treatment
Official Title: Open Label, Non-randomized, Phase IB Study to Characterize Safety, Tolerability and Recommended Dose of Tinostamustine and Nivolumab in Patients With Refractory, Locally Advanced or Metastatic MelAnoma
Actual Study Start Date : March 7, 2019
Estimated Primary Completion Date : December 15, 2021
Estimated Study Completion Date : March 15, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma
Drug Information available for: Nivolumab

Arm Intervention/treatment
Experimental: Tinostamustine and Nivolumab
Experimental drug combination arm
Drug: Tinostamustine
First-in-human administration of the combination of Tinostamustine and Nivolumab.
Other Name: Nivolumab

Primary Outcome Measures :
  1. Safety and dose-limiting toxicity [ Time Frame: at 6 weeks ]

    Dose limiting toxicity defined as any of the following AEs (according to CTCAE v 4.03) occurring during the first 42 days of study treatment for each study patient of the safety part of the trial, and regarded to be related (possibly, probably or definitely) to Tinostamustine:

    • CTC °4 neutropenia during ≥ 5 days
    • Febrile neutropenia
    • CTC °4 thrombocytopenia or CTC° 3 thrombocytopenia with bleeding
    • Any other ≥ CTC °4 hematological AE
    • ≥ CTC °3 AST or ALT elevations for >7 days, or CTC °4 AST/ALT elevations for any duration
    • ≥ CTC °3 nausea, vomiting or diarrhea despite appropriate pre-medication
    • Any other ≥ CTC °3 non-hematological study-treatment-related AE, excluding alopecia
    • ≥ CTC °3 uveitis, pneumonitis, bronchospasm, neurological toxicity, hypersensi-tivity reactions or infusion reactions that result in discontinuation of study treat-ment
    • Any study treatment-related AE that results in a delay of the administration of Tinostamustine of at least 4 weeks

Secondary Outcome Measures :
  1. Overall safety profile of the tinostamustine/nivolumab drug combination [ Time Frame: during a maximum 2 years of study treatment plus 100 days thereafter (3 years) ]
    All adverse events (AE) including laboratory safety parameters according to CTCAE v.4.03

  2. Radiological response [ Time Frame: every 8 weeks until progressive disease or end of study (5 years) ]
    Objective tumor response according to RECIST 1.1 and iRECIST

  3. Progression-free survival [ Time Frame: through study completion (5 years) ]
    Progression-free survival (PFS, iPFS), defined as the time between registration to the study and the time of disease progression according to RECIST v.1.1 and iRECIST or death of the patient, whatever occurs first

  4. Overall survival [ Time Frame: through study completion (5 years) ]
    Overall survival (OS) from registration of study participation

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Written informed consent
  • Patients with either histologically or cytologically confirmed inoperable stage III or metastatic stage IV melanoma
  • Indication for the regular systemic treatment with the anti-PD-1 monoclonal antibody Nivolumab monotherapy
  • Patient received a maximum of 1 prior systemic palliative line of treatment
  • ECOG ≤2
  • Patients with brain metastases must have undergone definitive treatment (surgery or radiotherapy) at least 2 weeks prior to starting study drug and be documented as having stable disease by imaging
  • Adequate bone marrow, renal and hepatic function
  • Adequate contraception

Exclusion Criteria:

  • Prior treatment with a PD-(L)1 targeted monoclonal antibody
  • Patients who have received systemic treatments or radiotherapy within 2 weeks prior to starting study drug
  • Concomittant treatment with systemic steroids at a daily dose equivalent to ≥10mg of prednisone, or concomittant treatment with immunosuppressive drugs such as methotrexate
  • Patients with a prior malignancy are excluded (except non-melanoma skin cancers, and in situ cancers such as the following: bladder, colon,cervical/dysplasia, melanoma, or breast). Patients with other second malignancies diagnosed more than 2 years ago who have received therapy with curative intent with no evidence of disease during the interval who are considered by the Investigator to present a low risk for recurrence will be eligible.
  • NYHA stage III/IV congestive heart failure and/or arrhythmia not adequately controlled
  • QTc interval (Fridericia's formula) > 450msec
  • Patients who are on treatment with drugs known to prolong the QT/QTc interval (Credible Meds list:

Known risk of TdP.

  • Pregnant and breast feeding patients

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03903458

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Contact: Elke Hiendlmeyer, Dr. 714941111 ext +41
Contact: Christina Jodlauk 714941111 ext +41

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Kantonsspital Graubünden Recruiting
Chur, Switzerland, 7000
Contact: Roger von Moos, Prof.    +41 81 256 66 46   
Principal Investigator: Roger von Moos, Prof.         
Cantonal Hospital St.Gallen Recruiting
St.Gallen, Switzerland, 9007
Contact: Elke Hiendlmeyer, Dr.    714941111 ext +41   
Contact: Christina Jodlauk    714941111 ext +41   
Principal Investigator: Markus Joerger, Prof.         
Sponsors and Collaborators
Markus Joerger
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Study Chair: Markus Joerger, Prof. Cantonal Hospital St. Gallen, Switzerland

Additional Information:
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Responsible Party: Markus Joerger, Chair Clinical Research Unit, Cantonal Hospital of St. Gallen Identifier: NCT03903458     History of Changes
Other Study ID Numbers: CTU 17.022
First Posted: April 4, 2019    Key Record Dates
Last Update Posted: April 8, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: N.A.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Markus Joerger, Cantonal Hospital of St. Gallen:
systemic anticancer treatment
epigenetic treatment
Additional relevant MeSH terms:
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Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Antineoplastic Agents, Immunological
Antineoplastic Agents