Clinical trial NCT03713320: SOLAR: Efficacy and Safety of Cobomarsen (MRG-106) vs. Active Comparator in Subjects With Mycosis Fungoides
Official title: SOLAR: A Phase 2, Randomized, Open-label, Parallel-group, Active Comparator, Multi-center Study to Investigate the Efficacy and Safety of Cobomarsen (MRG-106) in Subjects With Cutaneous T-Cell Lymphoma (CTCL), Mycosis Fungoides (MF) Subtype
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Cutaneous T-Cell Lymphoma/Mycosis Fungoides
Keywords: SOLAR
Cutaneous T-cell Lymphoma
CTCL
Mycosis Fungoides
Lymphoma
Lymphoma, T-cell
Lymphoma, T-cell, cutaneous
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms
MicroRNAs
Vorinostat
Histone Deacetylase Inhibitors
Lead sponsor: miRagen Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2018-10-19
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The main objective of this clinical trial is to study the efficacy and safety of cobomarsen (also known as MRG-106) for the treatment of cutaneous T-cell lymphoma (CTCL), mycosis fungoides (MF) subtype. Cobomarsen is designed to inhibit the activity of a molecule called miR-155 that may be important to the growth and survival of MF cancer cells. The study will compare the effects of cobomarsen to vorinostat, a drug that has been approved for the treatment of CTCL in the United States and several other countries.

Participants in the clinical trial will be randomly assigned to receive either weekly doses of cobomarsen by injection into a vein or daily oral doses of vorinostat. Participants will continue on their assigned treatment as long as there is no evidence of progression of their cancer. The effects of treatment will be measured based on changes in skin lesion severity, as well as the length of time that the subject's disease remains stable or improved, without evidence of disease progression. The safety and tolerability of cobomarsen will be assessed based on the frequency and severity of observed side effects.

Participants assigned to receive vorinostat who experience progression of their disease during their participation in this study may have the option to be treated with cobomarsen in an open-label, crossover arm of the same study if they meet the entry criteria for that part of the study.

Detailed description: Study Design:

Subjects will be randomly assigned in a 1:1 ratio to receive either cobomarsen or vorinostat. Approximately 126 subjects (63 per arm) are expected to be enrolled. Cobomarsen will be administered in the clinic by 2-hr intravenous infusion on Days 1, 3, 5 and 8, and weekly thereafter. Vorinostat will be dispensed to study subjects and taken as a daily oral dose according to the manufacturer's labeled dosing instructions. Treatment will continue until the subject becomes intolerant, develops clinically significant side effects, progresses, or the trial is terminated. An interim analysis will be conducted after approximately 40 subjects have been followed for a minimum of approximately 6 months. Enrollment will be suspended until the completion of the interim analysis.

Eligibility criteria: Key Inclusion Criteria:

* Biopsy-proven CTCL, MF subtype
* Clinical stage IB, II, or III, with staging based on screening assessments
* Minimum mSWAT score of 10 at screening
* Receipt of at least one prior therapy for CTCL

Key Exclusion Criteria:

* Previous enrollment in a cobomarsen study
* Prior therapy with vorinostat or other HDAC inhibitors, or contraindication to an HDAC inhibitor
* Sézary syndrome or mycosis fungoides with B2 involvement, defined as documented history of B2 and/or B2 staging at screening
* Evidence of large cell transformation
* Lymph node involvement at screening, unless radiologically or histologically confirmed to be nonmalignant
* Visceral involvement related to MF at screening

Primary outcomes:
measure: Percentage of Subjects Achieving an Objective Skin Response of at Least 4 Months Duration (ORR4)
timeFrame: Date of first dose through the earlier of last study visit or interim analysis data cut-off date of 12-Oct-2020, up to 16 months
Secondary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: Date of first dose through interim analysis data cut-off date of 12-Oct-2020, up to 16 months
measure: Complete Response Rate
timeFrame: Date of first dose through interim analysis data cut-off date of 12-Oct-2020, up to 16 months
measure: Time to Progression
timeFrame: Date of first dose through interim analysis data cut-off date of 12-Oct-2020, up to 16 months
measure: Time to Maximal Effect in mSWAT
timeFrame: Monthly from first dose through interim analysis data cut-off date of 12-Oct-2020, up to 16 months
measure: Objective Response Rate in the Skin of at Least 28-days Duration (ORR1)
timeFrame: Monthly from first dose through interim analysis data cut-off date of 12-Oct-2020, up to 16 months
measure: Percentage of Subjects Achieving ≥ 50% Improvement in mSWAT at 28 Days
timeFrame: 28 days after first dose
measure: Percentage of Subjects Achieving ≥ 50% Improvement in mSWAT at 4 Months
timeFrame: 4 months after first dose
measure: Time to ≥ 50% Improvement in mSWAT
timeFrame: Monthly from first dose through interim analysis data cut-off date of 12-Oct-2020, up to 16 months
measure: Duration of Response in Skin
timeFrame: Monthly from first dose through interim analysis data cut-off date of 12-Oct-2020, up to 16 months
measure: Pruritus Medication Utilization
timeFrame: Date of first dose through end of treatment or interim analysis data cut-off date of 12-Oct-2020, up to 16 months
Other outcomes:
measure: Peak Plasma Concentration (Cmax) of Cobomarsen - First Dose
timeFrame: 1, 1.92, 6, 24 and 48 hours post-dose after the first dose
measure: Peak Plasma Concentration (Cmax) of Cobomarsen - Week 5
timeFrame: 1, 1.92 and 6 hours post-dose after the Week 5 dose
measure: Area Under the Plasma Concentration vs. Time Curve (AUC) of Cobomarsen - Week 5
timeFrame: 1, 1.92 and 6 hours post-dose after the Week 5 dose
measure: Number of Participants With Anti-drug Antibody Generation
timeFrame: Date of first dose through interim analysis data cut-off date of 12-Oct-2020, up to 16 months
Locations:
city: Birmingham
country: United States
facility: The University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Mayo Clinic
state: Arizona
city: Duarte
country: United States
facility: City of Hope
state: California
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Orange
country: United States
facility: Chao Family Comprehensive Cancer Center at University of California, Irvine
state: California
city: New Haven
country: United States
facility: Smilow Cancer Hospital at Yale-New Haven
state: Connecticut
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Fairport
country: United States
facility: Rochester Skin Lymphoma Medical Group
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Columbus
country: United States
facility: The Ohio State University Comprehensive Cancer Center
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Fairfax
country: United States
facility: Inova Schar Cancer Institute
state: Virginia
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Nedlands
country: Australia
facility: Linear Clinical Research
city: Leuven
country: Belgium
facility: University Clinic UZ Leuven
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Montréal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Bordeaux
country: France
facility: Hôpital Saint André, CHU de Bordeaux
city: Paris
country: France
facility: Hôpital Saint-Louis
city: Pierre-Bénite
country: France
facility: Centre Hospitalier Lyon-Sud
city: Reims
country: France
facility: Hôpital Robert Dubré, CHU de Reims
city: Rouen
country: France
facility: Centre Hospitalier Universitaire de Rouen
city: Bologna
country: Italy
facility: Policlinico S. Orsola-Malpighi
city: Milano
country: Italy
facility: Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
city: Torino
country: Italy
facility: AOU Citta dell Salute e della Scienza di Torino
city: Barcelona
country: Spain
facility: Vall d'Hebron Institute of Oncology
city: Madrid
country: Spain
facility: Fundación Jiménez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Valencia
country: Spain
facility: Consorcio Hospital General Universitario Valencia
city: Birmingham
country: United Kingdom
facility: University Hospitals of Birmingham NHS Foundation Trust, Queen Elizabeth Hospital
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
city: London
country: United Kingdom
facility: Guy's and St. Thomas' NHS Foundation Trust, Cancer Center
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
Study officials:
affiliation: miRagen Therapeutics, Inc.
name: Diana M. Escolar, MD, FAAN
role: STUDY_DIRECTOR
References:
citation: Ganguly K, Kishore U, Madan T. Interplay between C-type lectin receptors and microRNAs in cellular homeostasis and immune response. FEBS J. 2021 Jul;288(14):4210-4229. doi: 10.1111/febs.15603. Epub 2020 Nov 7.
citation: Valipour A, Jager M, Wu P, Schmitt J, Bunch C, Weberschock T. Interventions for mycosis fungoides. Cochrane Database Syst Rev. 2020 Jul 7;7(7):CD008946. doi: 10.1002/14651858.CD008946.pub3.