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

NCT ID: NCT04225390

Last Updated: 2022-05-27

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 38 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-13
• Study Completion Date: 2023-07-31

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.

Conditions

Immunotherapy

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dacarbazine

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

Group Type: EXPERIMENTAL

Dacarbazine (DTIC)

Intervention Type: DRUG

Dacarbazine powder for IV solution

Interventions

Dacarbazine (DTIC)

Dacarbazine powder for IV solution

Intervention Type: DRUG

Other Intervention Names

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital Regensburg

OTHER

Sponsor Role: collaborator

Wuerzburg University Hospital

OTHER

Sponsor Role: collaborator

University of Erlangen-Nürnberg Medical School

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University Hospital

Erlangen, Bavaria, Germany

Site Status: RECRUITING

Countries

Germany

Central Contacts

Lucie Heinzerling, Prof. Dr. MPH

Role: CONTACT

lucie.heinzerling@uk-erlangen.de

+49 (0) 9131- 85 45 804

Facility Contacts

Lucie Heinzerling, Prof. Dr.

Role: primary

Lucie.Heinzerling@uk-erlangen.de

Other Identifiers

PROMIT

Identifier Type: -

Identifier Source: org_study_id