Trial Title:
Rintatolimod, Celecoxib and Interferon Alpha 2b With Pembrolizumab For the Treatment of Patients With Metastatic or Unresectable Triple Negative Breast Cancer
NCT ID:
NCT05756166
Condition:
Anatomic Stage IV Breast Cancer AJCC v8
Metastatic Triple-Negative Breast Carcinoma
Unresectable Triple-Negative Breast Carcinoma
Conditions: Official terms:
Carcinoma
Breast Neoplasms
Triple Negative Breast Neoplasms
Interferons
Interferon-alpha
Interferon alpha-2
poly(I).poly(c12,U)
Celecoxib
Pembrolizumab
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biopsy
Description:
Undergo tumor biopsy
Arm group label:
Cohort II (CMK, early pembrolizumab)
Other name:
BIOPSY_TYPE
Other name:
Bx
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Cohort I (CKM, pembrolizumab)
Arm group label:
Cohort II (CMK, early pembrolizumab)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Drug
Intervention name:
Celecoxib
Description:
Given PO
Arm group label:
Cohort I (CKM, pembrolizumab)
Arm group label:
Cohort II (CMK, early pembrolizumab)
Other name:
Benzenesulfonamide, 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-
Other name:
Celebrex
Other name:
SC-58635
Other name:
YM 177
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT scan
Arm group label:
Cohort I (CKM, pembrolizumab)
Arm group label:
Cohort II (CMK, early pembrolizumab)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized Tomography
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Biological
Intervention name:
Interferon Alpha-2
Description:
Given IV
Arm group label:
Cohort I (CKM, pembrolizumab)
Arm group label:
Cohort II (CMK, early pembrolizumab)
Other name:
Alpha-2-Interferon
Other name:
Alpha-2a Interferon
Other name:
IFN-Alpha-2
Other name:
IFN-AlphaA
Other name:
IFNA2
Other name:
IFNA2 Protein
Other name:
Interferon Alpha 2
Other name:
Interferon Alpha 2a
Other name:
Interferon Alpha 2b
Other name:
Interferon Alpha A
Other name:
Interferon Alpha-A
Other name:
LeIF A
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Cohort I (CKM, pembrolizumab)
Arm group label:
Cohort II (CMK, early pembrolizumab)
Other name:
Magnetic Resonance
Other name:
Magnetic Resonance Imaging Scan
Other name:
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Other name:
MR
Other name:
MR Imaging
Other name:
MRI
Other name:
MRI Scan
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Intervention type:
Biological
Intervention name:
Pembrolizumab
Description:
Given IV
Arm group label:
Cohort I (CKM, pembrolizumab)
Arm group label:
Cohort II (CMK, early pembrolizumab)
Other name:
Keytruda
Other name:
Lambrolizumab
Other name:
MK-3475
Other name:
SCH 900475
Intervention type:
Drug
Intervention name:
Rintatolimod
Description:
Given IV
Arm group label:
Cohort I (CKM, pembrolizumab)
Arm group label:
Cohort II (CMK, early pembrolizumab)
Other name:
Ampligen
Other name:
Atvogen
Summary:
This phase I/IIa trial tests the safety, side effects, and best dose of chemokine
modulation therapy (CKM) (rintatolimod, celecoxib, and interferon alpha 2b) in
combination with pembrolizumab for the treatment of patients with triple negative breast
cancer that has spread from where it first started (primary site) to other places in the
body (metastatic) or that cannot be removed by surgery (unresectable). CKM drugs such as
rintatolimod and interferon alpha 2b work to modify the immune response and tumor-related
processes, including tumor cell growth, blood vessel growth, and metastasis. Celecoxib is
an anti-inflammatory drug that can cause cell death and may reduce the growth of blood
vessels tumors need to grow and spread. Immunotherapy such as pembrolizumab, may help the
body's immune system attack the cancer, and may interfere with the ability of tumor cells
to grow and spread. Giving CKM therapy prior to pembrolizumab may direct the immune cells
to the cancer cells and maximize the effectiveness of pembrolizumab in patients with
metastatic or unresectable triple negative breast cancer.
Detailed description:
PRIMARY OBJECTIVE:
I. To evaluate the safety profile of modified CKM (celecoxib, rintatolimod and interferon
alpha-2b) regimen (replacement of INTRON [registered trademark] A, using alternative
source of interferon alpha-2b [IFNalpha2b]) combined with pembrolizumab therapy in
metastatic triple negative breast cancer patients.
SECONDARY OBJECTIVES:
I. To evaluate the efficacy of the CKM in combination with pembrolizumab in patients with
metastatic triple negative breast cancer (mTNBC) as compared to historic outcomes of
pembrolizumab and other anti-PD1/PD-L1 therapies alone, as determined by secondary
measures of efficacy including:
Ia. Progression-free survival (PFS); Ib. Overall survival (OS); Ic. Overall response rate
(ORR) to the combination therapy using Immune Modulated Response Evaluation Criteria in
Solid Tumors (iRECIST); Id. Disease control rate (DCR) using iRECIST.
EXPLORATORY OBJECTIVES:
I. Examine the immune analysis profile of CKM and pembrolizumab combination:
Ia. Examine the relationship of infiltrating CD4+ and CD8+ T cells and other immune and
genetic markers, and their associated PD-1, CD45RA or CD45RO levels; Ib. Correlate PD-L1
expression within both neoplastic and nonneoplastic stromal elements of the tumor
microenvironment to PFS, OS, ORR and adverse events (AEs); Ic. Correlate immune panel
results with ORR, PFS, OS and AEs.
II. Comparison of response assessment criteria for a prospective analysis:
IIa. Response evaluation criteria in solid tumors (RECIST) 1.1 response assessment; IIb.
iRECIST response assessment.
OUTLINE: This is a phase I dose escalation study of interferon alpha-2b followed by a
phase II study. Patients are assigned to 1 of 2 cohorts.
COHORT I: Patients receive rintatolimod intravenously (IV), celecoxib orally (PO),
interferon alpha-2b IV on days 0, 1, and 2 of week 1 and days 7, 8, and 9 of week 2 on
study. Patients receive pembrolizumab IV on day 9 and then every 3 weeks after that for
up to 4 doses on study. Patients also undergo computed tomography (CT) scan or magnetic
resonance imaging (MRI) at screening and follow-up and undergo blood sample collection
during screening and on study.
COHORT II: Patients receive rintatolimod IV, celecoxib PO, and interferon alpha-2b IV on
days 0, 1, and 2 of week 1 and days 7, 8, and 9 of week 2 on study. Patients receive
pembrolizumab IV on day 2 of week 1 and then every 3 weeks beginning in week 4 on study.
Patients also undergo CT scan or MRI at screening and follow-up, undergo blood sample
collection during screening and on study, and may undergo tumor biopsy at screening and
follow-up.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Age >= 18 years of age
- Have pathologically confirmed diagnosis of PDL-1-negative or PDL1 positive
unresectable or metastatic TNBC with no curative treatment options
- Have been informed of other treatment options
- Patient has lesion that can be biopsied and is willing to undergo the procedure as
part of the protocol. Note: For cohort 1 and cohort 2: Patient with accessible tumor
will be offered optional pre-treatment and post-treatment biopsies. Biopsies are
mandatory for cohort 3
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of =< 1
- Participants of child-bearing potential must agree to use adequate contraceptive
methods (e.g., hormonal or barrier method of birth control; abstinence) prior to
study entry. Should a woman become pregnant or suspect she is pregnant while she or
her partner is participating in this study, she should inform her treating physician
immediately
- Ability to swallow and retain oral medication
- Have measurable disease per RECIST 1.1 criteria present
- Any line of therapy allowed, radiologically confirmed progression
- No cancer-directed therapy for at least 3 weeks prior to study treatment
(bone-directed therapies are allowed)
- Platelets >= 100,000/uL
- Hemoglobin >= 9.0 g/dL
- Absolute neutrophil count (ANC) >= 1500/uL
- Total bilirubin =< institutional upper limit of normal (ULN)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])
and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =<
2.5 X institutional ULN
- Creatinine < ULN or, creatinine clearance >= 50 mL/min per Cockcroft-Gault equation
for patients with creatinine levels greater than ULN
- Participant must understand the investigational nature of this study and sign an
Independent Ethics Committee/Institutional Review Board approved written informed
consent form prior to receiving any study related procedure
Exclusion Criteria:
- Patients currently treated with systemic immunosuppressive agents, including
steroids (greater than equivalent of 10 mg daily of prednisone), are ineligible
until 3 weeks after removal from immunosuppressive treatment. (Inhaled steroids are
allowed.)
- Patients with active autoimmune disease or history of transplantation
- Pregnant or nursing female participants
- Unwilling or unable to follow protocol requirements
- Patients with known serious mood disorders. (Major depression diagnosis is an
exclusion. Other stable mood disorders on stable therapy for > 6 months or not
requiring therapy may be allowed after consultation with the principal
investigator.)
- Cardiac risk factors including:
- Patients experiencing cardiac event(s) (acute coronary syndrome, myocardial
infarction, or ischemia) within 3 months of signing consent. While our
published clinical studies involving short-term CKM did not indicate increased
risk of cardiac events, the CKM can induce flu-like symptoms, providing
justification for its avoidance in patients with recent cardiac events
- Patients with a New York Heart Association classification of III or IV
- Patients with a history of stroke
- History of upper gastrointestinal ulceration, upper gastrointestinal bleeding, or
upper gastrointestinal perforation within the past 3 years
- Prior allergic reaction or hypersensitivity to nonsteroidal antiinflammatory drug
(NSAIDs) or any drugs administered on protocol
- Any condition which in the investigator's opinion deems the participant an
unsuitable candidate to receive study drug
- Any patients with a positive antinuclear antibodies test will be excluded from study
- Has a known history of human immunodeficiency virus (HIV) infection
- Concurrent active hepatitis B (defined as hepatitis B antigen [HBsAg] positive
and/or detectable hepatitis B virus [HBV] deoxyribonucleic acid [DNA]) and hepatitis
C virus (defined as anti-hepatitis C virus [HCV] antibody [Ab] positive and
detectable HCV ribonucleic acid [RNA]) infection. Note: Hepatitis B and C screening
tests are not required unless known history of HBV and HCV infection
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Roswell Park Cancer Institute
Address:
City:
Buffalo
Zip:
14263
Country:
United States
Status:
Recruiting
Contact:
Last name:
Shipra Gandhi
Phone:
716-845-1486
Email:
Shipra.Gandhi@RoswellPark.org
Investigator:
Last name:
Shipra Gandhi
Email:
Principal Investigator
Start date:
February 16, 2024
Completion date:
June 30, 2025
Lead sponsor:
Agency:
Roswell Park Cancer Institute
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
Roswell Park Cancer Institute
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05756166
