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

Studien-Informationen Einschlusskriterien Studien-Rationale Geprüfte Regime

Rekrutierend

NCT-Nummer:
NCT04225390

Studienbeginn:
Januar 2020

Letztes Update:
27.05.2022

Wirkstoff:
Dacarbazine (DTIC)

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
University of Erlangen-Nürnberg Medical School

Collaborator:
University Hospital Regensburg, Wuerzburg University Hospital,

Kontakt

Lucie Heinzerling, Prof. Dr. MPH
Kontakt:
Phone: +49 (0) 9131- 85 45 804
E-Mail: lucie.heinzerling@uk-erlangen.de» Kontaktdaten anzeigen

Studienlocations
(1 von 1)

University Hospital
91054 Erlangen
(Bayern)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Lucie Heinzerling, Prof. Dr.
E-Mail: Lucie.Heinzerling@uk-erlangen.de» Ansprechpartner anzeigen

Studien-Informationen

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.

Ein-/Ausschlusskriterien

Inclusion Criteria:

1. Histologically confirmed metastatic melanoma

2. Progression after checkpoint inhibitor therapy (PD-1/PD-L1 or PD-1 + CTLA-4 blockade)

3. Accessible tumor metastases

4. ECOG 0 or 1

5. Adequate organ function

Exclusion Criteria:

1. Uvea melanoma, mucosal melanoma

2. Previous chemotherapy in metastatic disease

3. Previous response to checkpoint inhibitor therapy (PD-1/PD-L1 or PD-1 + CTLA-4

blockade) in metastatic disease

4. BRAF V600 mutation

5. Active brain metastases

6. Autoimmune disease requiring more than 10 mg prednisolone daily or other

immunosuppressive drugs

Studien-Rationale

Primary outcome:

1. Rate of participents with CR, PR, SD or PD (Time Frame - week 14):
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.

Secondary outcome:

1. Overall survival (OS) (Time Frame - up to 5 years):
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.

Geprüfte Regime

Dacarbazine (DTIC) (DTIC):
Dacarbazine powder for IV solution

Quelle: ClinicalTrials.gov

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