Clinical Trials /

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

NCT04225390

Description:

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.

Related Conditions:
  • Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 2

URL:

https://clinicaltrials.gov/show/NCT04225390

Trial Eligibility

Document

Title

  • Brief Title: Preconditioning of Tumor, Tumor Microenvironment and the Immune System to Immunotherapy
  • Official Title: A Phase 2, Single Arm Study on Dacarbazine (DTIC) Followed by Immunotherapy Re-challenge in Unresectable or Metastatic Melanoma With Primary Resistance to PD-1/PD-L1 or PD-1 + CTLA-4 Blockade

Clinical Trial IDs

  • ORG STUDY ID: PROMIT
  • NCT ID: NCT04225390

Conditions

  • Immunotherapy

Interventions

DrugSynonymsArms
Dacarbazine (DTIC)DTICDacarbazine

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
DacarbazineExperimentalDacarbazine (day1 and day21) 850 mg/m² i.v. followed by re-exposure to the previous immunotherapy
  • Dacarbazine (DTIC)

Eligibility Criteria

        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
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Rate of participents with CR, PR, SD or PD
Time Frame:week 14
Safety Issue:
Description: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 Measures

Measure:Overall survival (OS)
Time Frame:up to 5 years
Safety Issue:
Description: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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Erlangen-Nürnberg Medical School

Trial Keywords

  • immune checkpoint blockade
  • resistance
  • dacarbazine

Last Updated

January 14, 2021