Description:
This phase II trial studies how well domatinostat (4SC-202) works in combination with
avelumab in adult patients with advanced unresectable and/or metastatic Merkel Cell Carcinoma
that have progressed on a previous therapy with an anti-PD-(L)1 antibody
Title
- Brief Title: Domatinostat in Combination With Avelumab in Patients With Advanced Merkel Cell Carcinoma Progressing on Anti-PD-(L)1
- Official Title: A Phase II, Open Label Study to Investigate the Efficacy and Safety of Domatinostat in Combination With Avelumab in Patients With Advanced Unresectable/Metastatic Merkel Cell Carcinoma Progressing on Anti-PD-(L)1 Antibody Therapy
Clinical Trial IDs
- ORG STUDY ID:
4SC-202-3-2018
- SECONDARY ID:
2018-004788-30
- NCT ID:
NCT04393753
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| domatinostat in combination with avelumab | | domatinostat and avelumab |
Purpose
This phase II trial studies how well domatinostat (4SC-202) works in combination with
avelumab in adult patients with advanced unresectable and/or metastatic Merkel Cell Carcinoma
that have progressed on a previous therapy with an anti-PD-(L)1 antibody
Trial Arms
| Name | Type | Description | Interventions |
|---|
| domatinostat and avelumab | Experimental | Single arm study of Domatinostat tablets in combination with avelumab infusion | - domatinostat in combination with avelumab
|
Eligibility Criteria
Inclusion Criteria:
- Histologically confirmed Merkel Cell Carcinoma (MCC)
- ECOG performance status ≤ 1
- MCC in an advanced, unresectable stage III or metastatic stage IV (includes patients
who refused surgical resection or are not eligible for such surgical resection)
- Progressing on previous anti-PD-(L)1 antibody monotherapy within the last 12 weeks
before planned first administration of study medication
Exclusion Criteria:
- History of serious anti-PD-(L)1 therapy-related adverse reactions prohibiting further
avelumab treatment
- More than one line of previous systemic anti-neoplastic therapy other than
anti-PD-(L)1 antibody monotherapy
- Palliative radiation therapy of single lesions within 2 weeks before planned
administration of study medication
- Presence of significant active or chronic disease (infections, immunodeficiencies,
cardiovascular, psychiatric disorders)
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Objective Response Rate (ORR) |
| Time Frame: | up to 24 months |
| Safety Issue: | |
| Description: | Objective Response Rate (ORR) defined as the percentage of patients having a confirmed CR or PR according to RECIST v1.1 |
Secondary Outcome Measures
| Measure: | Durable Response Rate (DRR) |
| Time Frame: | up to 24 months |
| Safety Issue: | |
| Description: | Durable Response Rate (DRR), defined as the percentage of patients having a RECIST v1.1 response lasting ≥ 6 months |
| Measure: | Duration of Response (DoR) |
| Time Frame: | up to 24 months |
| Safety Issue: | |
| Description: | Duration of Response (DoR), defined as the time from an initial objective response (CR or PR) according to RECIST v1.1 until disease progression or death due to any cause |
| Measure: | Disease Control Rate (DCR) |
| Time Frame: | up to 24 months |
| Safety Issue: | |
| Description: | Disease Control Rate (DCR), defined as the proportion of patients with either an objective response (CR, PR) or stable disease (SD) according to RECIST v1.1. |
| Measure: | Durable Disease Control Rate (dDCR) |
| Time Frame: | up to 24 months |
| Safety Issue: | |
| Description: | Durable Disease Control Rate (dDCR), defined as the percentage of patients having a RECIST v1.1 disease control lasting ≥ 6 months |
| Measure: | Best Overall response (BOR) |
| Time Frame: | up to 24 months |
| Safety Issue: | |
| Description: | Best Overall response (BOR), defined as the best response (PD, SD, PR, CR) according to RECIST v1.1 over the course of a patient's participation in the study, assessed up to 2 years |
| Measure: | Progression Free Survival (PFS) |
| Time Frame: | up to 24 months |
| Safety Issue: | |
| Description: | Progression Free Survival (PFS), defined as the time from first dosing (Day +1) to the date of PD or death from any cause (whichever comes first) |
| Measure: | PFS Rate |
| Time Frame: | up to 24 months |
| Safety Issue: | |
| Description: | PFS Rate, defined as the percentage of patients without PD at 6 and 12 months after first administration of study drug |
| Measure: | Overall Survival (OS) |
| Time Frame: | up to 36 months |
| Safety Issue: | |
| Description: | Overall Survival (OS), defined as the time from the first administration of study medication until death due to any cause |
| Measure: | OS Rate |
| Time Frame: | up to 12 months |
| Safety Issue: | |
| Description: | OS Rate, defined as the percentage of patients alive at 6 and at 12 months after first administration of study drug |
| Measure: | Safety and Tolerability |
| Time Frame: | up to 24 months |
| Safety Issue: | |
| Description: | Safety and Tolerability of the study medication (determined by number, frequency, duration and severity of AEs using CTCAE v5.0, physical examination, laboratory tests, vital signs, and ECGs) |
| Measure: | Health related Quality of Life (HrQoL) |
| Time Frame: | up to 24 months |
| Safety Issue: | |
| Description: | The impact of treatment on the patient's QoLwill be assessed with the questionnaires "Functional Assessment of Cancer Therapy - Melanoma (FACT-M)" where QoL is assessed on a scale 0-240 (higher score means better status of health), with "EQ-5D-5L" which is a multi attribute utility instrument for measuring health-related QoL as EQ5D index with a score 0-1 (higher score means better status of health) and with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) with a score 0-100 per subscale (n=9 per item (n=6), higher score means better QoL. |
| Measure: | Plasma concentration of domatinostat and avelumab |
| Time Frame: | up to 48 weeks |
| Safety Issue: | |
| Description: | Single trough values of domatinostat and avelumab at pre-defined time points |
| Measure: | Avelumab anti-drug antibodies (ADA) |
| Time Frame: | up to 48 weeks |
| Safety Issue: | |
| Description: | Avelumab anti-drug antibodies (ADA) |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | 4SC AG |
Last Updated
June 29, 2021
