Preconditioning of Tumor, Tumor Microenvironment and the... | NCT04225390

Studies
Preconditioning of Tumor, Tumor Microenvironment and the Immune System to Immunotherapy

NCT04225390

Sponsor

University of Erlangen-Nürnberg Medical School

Status

Completed

Last Update Posted

Feb 10, 2026Actual

Enrollment

38Actual

Phase

Phase 2

Conditions

Immunotherapy

Interventions

Dacarbazine (DTIC)

Countries

Germany

Protocol Section

Identification Module Status Module Sponsor/Collaborators Module Oversight Module Description Module Conditions Module Design Module Arms/Interventions Module Outcomes Module Eligibility Module Contacts/Locations Module References Module IPD Sharing Statement Module

Results Section

Participant Flow Module Baseline Characteristics Module Outcome Measures Module Adverse Events Module More Info Module

Annotation Section

Annotation Module

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module Condition Browse Module Intervention Browse Module

Protocol Section

Identification Module

NCT ID

Results Section

No data available

No data is available for this block.

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Version Holder

Status Module

Record Verification Date

Jan 2026

Overall Recruitment Status or Expanded Access Status

Completed

Last Known Status

Not provided

Delayed Posting

Not provided

Why Stopped

Not provided

Expanded Access Info

Start Date

Jan 13, 2020Actual

Primary Completion Date

Jan 15, 2026Actual

Completion Date

Jan 15, 2026Actual

First Submitted Date

Jan 3, 2020

First Submission Date that Met QC Criteria

Jan 8, 2020

First Posted Date

Jan 13, 2020Actual

Results Waived

Not provided

Results First Submitted Date

Not provided

Results First Submitted that Met QC Criteria

Not provided

Results First Posted Date

Not provided

Certification/Extension (aka Delayed Results) First Submitted Date

Not provided

Certification/Extension First Submitted that Passed QC Review

Not provided

Certification/Extension First Posted Date

Not provided

Last Update Submitted Date

Feb 6, 2026

Last Update Posted Date

Feb 10, 2026Actual

Sponsor/Collaborators Module

Responsible Party, by Official Title

Sponsor

Lead Sponsor

University of Erlangen-Nürnberg Medical SchoolOTHER

Collaborators

Name	Class
University Hospital Regensburg	OTHER
Wuerzburg University Hospital	OTHER
Ludwig-Maximilians - University of Munich	OTHER

Oversight Module

Has Data Monitoring Committee (DMC)

Yes

Is FDA Regulated Drug

Is FDA Regulated Device

Is Unapproved Device

Not provided

Pediatric Postmarket Surveillance of a Device Product

Not provided

Product Exported from US

FDAAA801 Violation

Not provided

Description Module

Brief Summary

PROMIT is a single arm phase 2 trial evaluating the clinical activity of immune checkpoint blockade (ICB) after administration of dacarbazine (DTIC) in patients with unresectable or metastatic, BRAF wildtype melanoma with primary resistance to anti-programmed-cell-death-1 (PD-1/PD-L1) or PD-1 plus anti-cytotoxic-T-lymphocyte antigen 4 (CTLA-4) blockade therapy. If the activity is clinically meaningful, DTIC could become a new therapeutic option to break primary resistance to immunotherapy.

Detailed Description

PROMIT is a phase 2, single arm, open label study of DTIC followed by combined immune checkpoint blockade (ICB) therapy or PD-1/PD-L1-blockade monotherapy in adult (≥ 18 years) subjects with previously treated, unresectable or metastatic melanoma (Stage III or Stage IV melanoma as per the AJCC staging system). Subjects must be BRAF wildtype and must have shown primary resistance to ICB. Fresh tumor tissue from an unresectable or metastatic site of disease must be available.

Subjects will be treated with DTIC 850 mg/m² day 1 and 21 i.v. (DTIC phase). Afterwards, patients will receive combined ipilimumab (3 mg/kg) and nivolumab (1 mg/kg) 4 times every 3 weeks i.v. OR nivolumab 240 mg every 2 weeks OR pembrolizumab 200 mg every 3 weeks (ICB re-exposure phase; EMA-approved dosing scheme). By the end of the ICB phase, response will be documented (primary endpoint). A safety follow-up for treatment-related adverse events will be performed until 30 days after the last dose of combined ICB. Patients will be followed for survival every 12 weeks after the end of the combined ICB phase (second primary endpoint). Tumor and blood samples will be assessed over the course of the study to evaluate changes in tumor, tumor microenvironment and immune system.

Design Module

Study Type

Interventional

Number of References to an Expanded Access Study

Not provided

Expanded Access Types

Not provided

Patient Registry

Not provided

Target Follow-Up Duration

Not provided

Phases

Phase 2

Interventional Study Design

Allocation

Biospecimen

No data available

No data is available for this block.

Enrollment

38Actual

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Dacarbazine	Experimental	Dacarbazine (day1 and day21) 850 mg/m² i.v. followed by re-exposure to the previous immunotherapy	Drug: Dacarbazine (DTIC)

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Dacarbazine (DTIC)	Drug	Dacarbazine powder for IV solution	Dacarbazine

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Rate of participents with CR, PR, SD or PD	A patient is defined as responder if a complete response (CR) or partial response (PR) can be seen. A patient with stable disease (SD) or progressive disease (PD) will be defined as non-responder.	week 14

Secondary Outcomes

Measure	Description	Time Frame
Overall survival (OS)	Overall survival (OS), defined as the time between study inclusion and date of death (any cause). For subjects without documentation of death, OS will be censored on the last date the subject was known to be alive. OS will be followed continuously while subjects are on the study drug and every 12 weeks via phone contact after subjects discontinue the treatment phase.	up to 5 years

Other Outcomes

Not provided

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Histologically confirmed metastatic melanoma
Progression after checkpoint inhibitor therapy (PD-1/PD-L1 or PD-1 + CTLA-4 blockade)
Accessible tumor metastases
ECOG 0 or 1
Adequate organ function

Exclusion Criteria:

Uvea melanoma, mucosal melanoma
Previous chemotherapy in metastatic disease
Previous response to checkpoint inhibitor therapy (PD-1/PD-L1 or PD-1 + CTLA-4 blockade) in metastatic disease
BRAF V600 mutation
Active brain metastases
Autoimmune disease requiring more than 10 mg prednisolone daily or other immunosuppressive drugs

Accepts Healthy Volunteers

Sex

All

Sex/Gender Based

Not provided

Sex/Gender Description

Not provided

Minimum Age

18 Years

Maximum Age

Not provided

Standard Ages

AdultOlder Adult

Study Population

Not provided

Sampling Method

Not provided

Contacts/Locations Module

Central Contacts

Not provided

Overall Officials

Not provided

Locations

Facility	Status	City	State	ZIP	Country	Contacts
University Hospital		Erlangen	Bavaria	91054	Germany

Intervention Browse Module

MeSH Terms

ID	Term
D003606	Dacarbazine

Ancestor Terms

ID	Term
D014226	Triazenes
D009930	Organic Chemicals
D007093	Imidazoles
D001393	Azoles
D006573

Browse Leaves

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Browse Branches

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