Trial Title:
A Phase II Study of All-Trans Retinoic Acid (ATRA) and Cemiplimab in Patients With Advanced Leiomyosarcoma
NCT ID:
NCT06528769
Condition:
Leiomyosarcoma
Sarcoma
Conditions: Official terms:
Leiomyosarcoma
Vitamin A
Tretinoin
Cemiplimab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
all-trans retinoic acid
Description:
Given orally
Arm group label:
Treatment (all-trans retinoic acid [ATRA] and cemiplimab)
Other name:
ATRA
Other name:
retinoic acid
Other name:
tretinoin
Other name:
vitamin A acid
Intervention type:
Drug
Intervention name:
Cemiplimab
Description:
Given intravenously (IV)
Arm group label:
Treatment (all-trans retinoic acid [ATRA] and cemiplimab)
Other name:
libtayo
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT
Arm group label:
Treatment (all-trans retinoic acid [ATRA] and cemiplimab)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Procedure
Intervention name:
Magnetic resonance imaging
Description:
Undergo MRI
Arm group label:
Treatment (all-trans retinoic acid [ATRA] and cemiplimab)
Other name:
MRI
Other name:
MRI scan
Summary:
A phase 2 study assessing the efficacy of all-trans retinoic acid (ATRA) and Cemiplimab
in patients with metastatic/locally advanced - unresectable leiomyosarcoma (LMS) who have
progressed standard-of-care therapy. Patients will be enrolled in cohorts according to a
Bayesian Optimal Phase II design (BOP2).
Study treatment will consist of ATRA at a starting dose of 150 mg/m2/day for 3 days
orally prior to each cycle of Cemiplimab 350 mg IV q3 weeks for three cycles and then
Cemiplimab monotherapy until the progress of disease or unacceptable toxicities develops.
Detailed description:
PRIMARY OBJECTIVES
I. To determine the efficacy of the combination of ATRA and Cemiplimab in patients with
metastatic/locally advanced -unresectable LMS by assessing objective response (ORR),
based on modified RECIST version 1.1 and iRECIST
SECONDARY OBJECTIVES
I. To study the efficacy of the combination of ATRA and Cemiplimab in patients with
advanced LMS, including progression-free survival (PFS), disease control rate (DCR), and
overall survival (OS) based on modified RECIST version 1.1 and iRECIST.
II. To determine the safety and tolerability of the combination of ATRA and Cemiplimab in
patients with metastatic/locally advanced -unresectable LMS based upon the Common
Terminology Criteria for Adverse Events (CTCAE) version 5 criteria.
EXPLORATORY OBJECTIVES
I. To study the effect of ATRA on the levels of myeloid-derived suppressor cells (MDSCs)
in the peripheral blood of study patients.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Age ≥18 years
- Confirmed metastatic or locally advanced - unresectable Leiomyosarcoma (LMS)
- Measurable disease based on RECIST 1.1. (At least one target lesion)
- Patients must have received standard of care chemotherapy. No limits to prior lines
of therapy.
- Prior PD-1 and/or PD-L1 directed therapies are permitted. Minimal wash out period of
3 weeks for Pembrolizumab, Nivolumab , Durvalumab, 4 weeks for Ipilimumab.
- ECOG performance status of 0-2.
- Adequate organ function, as defined below.
- Absolute neutrophil count (ANC) ≥ 1,500 /mcL, hemoglobin ≥9 g/dL (patients may
be transfused to meet this criterion), lymphocytes ≥ 500/mcL, platelets ≥
100,000/mcL
- Serum creatinine ≤ 1.5 X upper limit of normal (ULN) or measured or calculated
creatinine clearance (CrCl) ≥ 60 mL/min for patients with creatinine levels >
1.5 X ULN (glomerular filtration rate [GFR] can also be used in place of
creatinine or CrCl)
- Serum total bilirubin ≤ 1.5 X ULN or direct bilirubin ≤ ULN for patients with
total bilirubin levels > 1.5 X ULN. FOr patients with known Gilbert disease,
serum bilirubin ≤ 3 X ULN
- Aspartate aminotransferase (AST) and alanine transaminase (ALT) ≤ 2.5 X ULN or
≤ 5 X ULN for patients with liver metastases
- albumin ≥ 2.5 g/dL
- International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN unless
patients is receiving anticoagulant therapy as long as PT or PTT is within
therapeutic range of intended use of anticoagulants
- Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless the patients is
receiving anticoagulant therapy as long as PT or PTT is within therapeutic
range of intended use of anticoagulants
- Anticipated life expectancy of ≥ 6 months.
- Willing to comply with study procedures
- Female patients of childbearing potential should have a negative urine or serum
pregnancy within 14 days prior to receiving the first dose of study medication. If
the urine test is positive or cannot be confirmed as negative, a serum pregnancy
test will be required.
- Be willing and able to understand and sign the written informed consent document.
- Ability to swallow and retain oral medication.
- HIV-infected patients on effective anti-retroviral therapy with undetectable viral
load within 6 months are eligible for this trial. Testing not indicated for patients
without known history of HIV.
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV
viral load must be undetectable on suppressive therapy, if indicated. Testing not
indicated for patients without known history of HBV.
- Patients with a history of hepatitis C virus (HCV) infection must have been treated
and cured. Testing not indicated for patients without known history of HCV.
Exclusion Criteria:
- Is currently participating and receiving study therapy or has participated in a
study of an investigational agent and received study therapy or used an
investigational device within 4 weeks of the first dose of treatment.
- Active or history of autoimmune disease or immune deficiency, including, but not
limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus
erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid
antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré
syndrome, or multiple sclerosis with the following exceptions:
- Patients with a history of autoimmune-related hypothyroidism who are stable on
thyroid-replacement hormone are eligible for the study
- Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen
are eligible for the study.
- Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with
dermatologic manifestations only (e.g., patients with psoriatic arthritis are
excluded) are eligible for the study provided all of following conditions are
met:
- Rash must cover ≤ 10% of body surface area
- Disease is well controlled at baseline and requires only low-potency
topical corticosteroids
- No occurrence of acute exacerbations of the underlying condition requiring
psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic
agents, oral calcineurin inhibitors, or high-potency or oral
corticosteroids within the previous 12 months
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy at
doses > 10 mg prednisone or equivalent or other form of immunosuppressive therapy
within 14 days prior to the first dose of trial treatment.
- Cirrhosis (Child-Pugh B or worse) or cirrhosis with history of hepatic
encephalopathy or clinically meaningful ascites resulting from cirrhosis. Clinically
meaningful ascites is defined as ascites from cirrhosis requiring increasing dosage
of diuretics or paracentesis.
- Has symptomatic central nervous system (CNS) metastases and/or carcinomatous
meningitis. Patients with asymptomatic CNS lesions will be eligible if considered
appropriate by the treating physician. Patients with previously treated brain
metastases may participate provided they have had a stable neurological status for
at least 2 weeks after completion of definitive therapy. Patients may be on
corticosteroids (≤ 10 mg of prednisone-equivalent) to control brain metastases if
they have been on a stable dose for 2 weeks (14 days) prior to the start of study
treatment and are clinically asymptomatic. This exception does not include
carcinomatous meningitis which is excluded regardless of clinical stability.
- Pregnancy or breastfeeding or intention of becoming pregnant during study treatment
or within 180 days for Cemiplimab after the final dose of study treatment
- Women of childbearing potential must have a negative serum pregnancy test
result within 14 days prior to initiation of study treatment.
- Highly effective contraception should be used in women of childbearing
potential during treatment with Cemiplimab and for at least 6 months following
the last dose of Cemiplimab.
- Any patient who has experienced unacceptable toxicity on prior checkpoint inhibitor
therapy as detailed below:
1. ≥ Grade 3 AE related to checkpoint inhibitor.
2. Ongoing ≥ Grade 2 immune-related AE associated with checkpoint inhibitor with
the exception of endocrine toxicities as detailed below.
3. CNS, ocular or cardiac AE of any grade related to checkpoint inhibitor. * NOTE:
Patients with a prior or ongoing endocrine AE are permitted to enroll if they
are stably maintained on appropriate replacement therapy and are asymptomatic.
- History of migraines requiring treatment within 3 months of study entry.
- History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis
obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of
active pneumonitis on screening chest computed tomography (CT) scan
- History of radiation pneumonitis in the radiation field (fibrosis) is
permitted.
- Significant cardiovascular disease (such as New York Heart Association Class II or
greater cardiac disease, myocardial infarction, or cerebrovascular accident) within
6 months prior to initiation of study treatment, unstable arrhythmia, or unstable
angina
- Major surgical procedure, other than for diagnosis, within 8 weeks prior to
initiation of study treatment, or anticipation of need for a major surgical
procedure during the study
- Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation
of study treatment. Patients receiving prophylactic antibiotics (e.g., to prevent a
urinary tract infection or chronic obstructive pulmonary disease exacerbation) are
eligible for the study.
- Prior allogeneic stem cell or solid organ transplantation
- Live, attenuated vaccines (e.g., FluMist®) are prohibited within 4 weeks prior to
initiation of study treatment, during treatment with Cemiplimab, and for 5 months
after the last dose of Cemiplimab.
- Current treatment with anti-viral therapy for HBV
- Has had prior chemotherapy, immunotherapy, targeted small molecule therapy, or
radiation therapy within 2 weeks prior to study Day 1
- History of severe allergic anaphylactic reactions to human antibodies.
- Known hypersensitivity to Chinese hamster ovary cell products or to any component of
the Cemiplimab formulation
- Known allergy or hypersensitivity to any component of ATRA
- Has a history or current evidence of any condition, therapy, or laboratory
abnormality that might confound the results of the trial, interfere with the
patient's participation for the full duration of the trial, or is not in the best
interest of the patient to participate, in the opinion of the treating investigator.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Ohio State University Comprehensive Cancer Center
Address:
City:
Columbus
Zip:
43210
Country:
United States
Contact:
Last name:
Gabriel Tinoco, MD
Email:
Gabriel.Tinoco@osumc.edu
Investigator:
Last name:
Gabriel Tinoco, MD
Email:
Principal Investigator
Start date:
December 1, 2024
Completion date:
December 31, 2025
Lead sponsor:
Agency:
Gabriel Tinoco
Agency class:
Other
Source:
Ohio State University Comprehensive Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06528769
http://cancer.osu.edu
