Malignant MelanomaPhase 1ENIgMANCT03903458
Tinostamustine and Nivolumab in Advanced Melanoma
A Phase 1 study testing Tinostamustine in people with Malignant Melanoma, run by Markus Joerger at 2 sites in Switzerland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Melanoma
- What is being tested?
- Tinostamustine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 2 sitesSwitzerland
- Study dates
- 7 Mar 2019to 15 Mar 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
Switzerland2 sites, 2 recruiting
- Recruiting
Kantonsspital Graubünden
Chur, 7000
Roger von Moos, Prof., +41 81 256 66 46, rogervonmoos@ksgr.ch
Roger von Moos, Prof.
- Recruiting
Cantonal Hospital St.Gallen
Sankt Gallen, 9007
Elke Hiendlmeyer, Dr., 714941111 ext. +41, elke.hiendlmeyer@kssg.ch
Christina Jodlauk, 714941111 ext. +41, christina.jodlauk@kssg.ch
About this study
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
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.
Read the 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.
- Conditions
- Malignant Melanoma
- Being tested
- Tinostamustine
- Keywords
- systemic anticancer treatment, immunotherapy, epigenetic treatment
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TinostamustineDrug
Also called Nivolumab
First-in-human administration of the combination of Tinostamustine and Nivolumab.
| Study group | Role | What they receive |
|---|---|---|
| Tinostamustine and Nivolumab | Experimental | Experimental drug combination arm Receives: Drug: Tinostamustine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: at 6 weeks
Secondary outcomes (4)
Overall safety profile of the tinostamustine/nivolumab drug combination
All adverse events (AE) including laboratory safety parameters according to CTCAE v.4.03
Measured: during a maximum 2 years of study treatment plus 100 days thereafter (3 years)
Radiological response
Objective tumor response according to RECIST 1.1 and iRECIST
Measured: every 8 weeks until progressive disease or end of study (5 years)
Progression-free survival
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
Measured: through study completion (5 years)
Overall survival
Overall survival (OS) from registration of study participation
Measured: through study completion (5 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2019
- Study start7 Mar 2019
- Primary completion15 Dec 2021 (estimated)
- Study completion15 Mar 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Malignant MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- this is an open label, non-randomized, Phase IB clinical trial studying a new anticancer drug combination
- Masking
- None (open label)
- Enrolment
- 21 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Markus Joerger
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Markus Joerger, Cantonal Hospital of St. Gallen
- Investigators
- Markus Joerger, Prof., Study chair, Cantonal Hospital of St. Gallen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03903458
- Sponsor's protocol ID
- CTU 17.022
- Acronym
- ENIgMA
- Status last verified
- Apr 2019
- First submitted
- 13 Mar 2019
- Last updated
- 8 Apr 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03903458
- Acronym / sponsor ID
- ENIgMA / CTU 17.022
- Conditions
- Malignant Melanoma
- Keywords
- systemic anticancer treatment, immunotherapy, epigenetic treatment
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 21 participants (estimated)
- Lead sponsor
- Markus JoergerUniversity, hospital or other
- Study start
- 7 Mar 2019 (actual)
- Primary completion
- 15 Dec 2021 (estimated)
- Study completion
- 15 Mar 2024 (estimated)
- First posted
- 4 Apr 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- this is an open label, non-randomized, Phase IB clinical trial studying a new anticancer drug combination
| Arm | Type | Receives |
|---|---|---|
| Tinostamustine and Nivolumab | Experimental | Drug: TinostamustineExperimental drug combination arm |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TinostamustineAlso: NivolumabFirst-in-human administration of the combination of Tinostamustine and Nivolumab. | Drug | Tinostamustine and Nivolumab |
Primary outcome
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
4 secondary outcomes
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)
Radiological response
Time frame: every 8 weeks until progressive disease or end of study (5 years)
Progression-free survival
Time frame: through study completion (5 years)
Overall survival
Time frame: through study completion (5 years)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Apr 2019.
- Clinical Trials Unit St. Gallen, SwitzerlandLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Markus Joerger, Prof. study chair
Cantonal Hospital of St. Gallen
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Tinostamustine in people with Malignant Melanoma, run by Markus Joerger at 2 sites in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 8 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Elke Hiendlmeyer, Dr. (714941111 ext. +41, elke.hiendlmeyer@kssg.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and dose-limiting toxicity (time frame: at 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Apr 2019.