Tinostamustine and Nivolumab in Advanced Melanoma

NCT03903458 | Unknown Phase 1

• 1 other identifier: CTU 17.022
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 2

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.

Conditions

Malignant Melanoma

Keywords

systemic anticancer treatment; immunotherapy; epigenetic treatment

Outcome Measures

Primary Outcomes (1)

• Safety and dose-limiting toxicity

  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

  at 6 weeks

Secondary Outcomes (4)

• Overall safety profile of the tinostamustine/nivolumab drug combination

  during a maximum 2 years of study treatment plus 100 days thereafter (3 years)

• Radiological response

  every 8 weeks until progressive disease or end of study (5 years)

• Progression-free survival

  through study completion (5 years)

• Overall survival

  through study completion (5 years)

Study Arms (1)

Tinostamustine and Nivolumab

EXPERIMENTAL

Experimental drug combination arm

Drug: Tinostamustine

Interventions

Tinostamustine DRUG

First-in-human administration of the combination of Tinostamustine and Nivolumab.

Also known as: Nivolumab

Tinostamustine and Nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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. https://www.crediblemeds.org).
• Pregnant and breast feeding patients

Sponsors & Collaborators

• Markus Joerger: lead

Study Sites (2)

Kantonsspital Graubünden

Chur, 7000, Switzerland

RECRUITING

Cantonal Hospital St.Gallen

Sankt Gallen, 9007, Switzerland

RECRUITING

Related Links

• Clinical Trials Unit St. Gallen, Switzerland

MeSH Terms

Conditions

Melanoma

Interventions

tinostamustine; Nivolumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Markus Joerger, Prof.

  Cantonal Hospital of St. Gallen

  STUDY CHAIR

Central Study Contacts

Elke Hiendlmeyer, Dr.

CONTACT

714941111; elke.hiendlmeyer@kssg.ch

Christina Jodlauk

CONTACT

714941111; christina.jodlauk@kssg.ch

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: open-label
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chair Clinical Research Unit

Model Details: this is an open label, non-randomized, Phase IB clinical trial studying a new anticancer drug combination

Study Record Dates

• First Submitted: March 13, 2019
• First Posted: April 4, 2019
• Study Start: March 7, 2019
• Primary Completion: December 15, 2021
• Study Completion: March 15, 2024
• Last Updated: April 8, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share

Locations

CH (2)