- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05756166
Rintatolimod, Celecoxib and Interferon Alpha 2b With Pembrolizumab For the Treatment of Patients With Metastatic or Unresectable Triple Negative Breast Cancer
Phase I/IIa Clinical Trial Evaluating the Safety and Efficacy of Rintatolimod Combined With IFNα2b (Bioferon®) to Enhance the Effectiveness of Pembrolizumab in Patients With Metastatic Triple Negative Breast Cancer
Study Overview
Status
Conditions
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.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
New York
-
Buffalo, New York, United States, 14263
- Recruiting
- Roswell Park Cancer Institute
-
Contact:
- Shipra Gandhi
- Phone Number: 716-845-1486
- Email: Shipra.Gandhi@roswellpark.org
-
Principal Investigator:
- Shipra Gandhi
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Cohort I (CKM, pembrolizumab)
Patients receive rintatolimod IV, celecoxib 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 CT scan or MRI at screening and follow-up and undergo blood sample collection during screening and on study.
|
Undergo MRI
Other Names:
Given IV
Other Names:
Undergo blood sample collection
Other Names:
Undergo CT scan
Other Names:
Given PO
Other Names:
Given IV
Other Names:
Given IV
Other Names:
|
Experimental: Cohort II (CMK, early pembrolizumab)
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.
|
Undergo MRI
Other Names:
Undergo tumor biopsy
Other Names:
Given IV
Other Names:
Undergo blood sample collection
Other Names:
Undergo CT scan
Other Names:
Given PO
Other Names:
Given IV
Other Names:
Given IV
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of adverse events
Time Frame: Up to 2 years
|
The dose limiting toxicities will be summarized by cohort using frequencies and relative frequencies.
|
Up to 2 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression-free survival
Time Frame: From the start of post-chemokine modulation (CKM) therapy therapy until disease progression, death, or lst follow-up, assessed up to 2 years
|
Will be summarized using standard Kaplan-Meier methods, with estimates of the median survival obtained with 90% confidence intervals.
|
From the start of post-chemokine modulation (CKM) therapy therapy until disease progression, death, or lst follow-up, assessed up to 2 years
|
Overall response rate
Time Frame: From the start of study treatment until end of treatment or disease progression/recurrence, assessed up to 2 years
|
Evaluated using Immune Modulated Response Evaluation Criteria in Solid Tumors.
Will be summarized using frequencies and relative frequencies, and obtained with 90% confidence intervals.
|
From the start of study treatment until end of treatment or disease progression/recurrence, assessed up to 2 years
|
Overall survival
Time Frame: From the start of post-CKM therapy until death due to any cause or last follow up, assessed up to 2 years
|
Will be summarized using standard Kaplan-Meier methods, with estimates of the median survival obtained with 90% confidence intervals.
|
From the start of post-CKM therapy until death due to any cause or last follow up, assessed up to 2 years
|
Disease control rate
Time Frame: Up to 2 years
|
Will be summarized using frequencies and relative frequencies and obtained with 90% confidence intervals.
|
Up to 2 years
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Shipra Gandhi, Roswell Park Cancer Institute
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Skin Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Breast Diseases
- Breast Neoplasms
- Carcinoma
- Triple Negative Breast Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Peripheral Nervous System Agents
- Antiviral Agents
- Enzyme Inhibitors
- Analgesics
- Sensory System Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Cyclooxygenase Inhibitors
- Antineoplastic Agents
- Immunologic Factors
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Cyclooxygenase 2 Inhibitors
- Interferons
- Interferon-alpha
- Interferon alpha-2
- Celecoxib
- Pembrolizumab
- poly(I).poly(c12,U)
Other Study ID Numbers
- I-3010822 (Other Identifier: Roswell Park Cancer Institute)
- P01CA234212 (U.S. NIH Grant/Contract)
- NCI-2023-01262 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Anatomic Stage IV Breast Cancer AJCC v8
-
M.D. Anderson Cancer CenterCompletedAnatomic Stage I Breast Cancer AJCC v8 | Anatomic Stage IA Breast Cancer AJCC v8 | Anatomic Stage IB Breast Cancer AJCC v8 | Anatomic Stage II Breast Cancer AJCC v8 | Anatomic Stage IIA Breast Cancer AJCC v8 | Anatomic Stage IIB Breast Cancer AJCC v8 | Anatomic Stage III Breast Cancer AJCC v8 | Anatomic... and other conditionsUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Active, not recruitingAnatomic Stage I Breast Cancer AJCC v8 | Anatomic Stage IA Breast Cancer AJCC v8 | Anatomic Stage IB Breast Cancer AJCC v8 | Anatomic Stage II Breast Cancer AJCC v8 | Anatomic Stage IIA Breast Cancer AJCC v8 | Anatomic Stage IIB Breast Cancer AJCC v8 | Anatomic Stage III Breast Cancer AJCC v8 | Anatomic... and other conditionsUnited States
-
Ohio State University Comprehensive Cancer CenterRecruitingAnatomic Stage I Breast Cancer AJCC v8 | Anatomic Stage IA Breast Cancer AJCC v8 | Anatomic Stage IB Breast Cancer AJCC v8 | Anatomic Stage II Breast Cancer AJCC v8 | Anatomic Stage IIA Breast Cancer AJCC v8 | Anatomic Stage IIB Breast Cancer AJCC v8 | Anatomic Stage III Breast Cancer AJCC v8 | Anatomic... and other conditionsUnited States
-
Jonsson Comprehensive Cancer CenterNovartis; Seagen Inc.RecruitingAnatomic Stage II Breast Cancer AJCC v8 | Anatomic Stage IIA Breast Cancer AJCC v8 | Anatomic Stage IIB Breast Cancer AJCC v8 | Anatomic Stage III Breast Cancer AJCC v8 | Anatomic Stage IIIA Breast Cancer AJCC v8 | Anatomic Stage IIIB Breast Cancer AJCC v8 | Anatomic Stage IIIC Breast Cancer AJCC... and other conditionsUnited States
-
Ohio State University Comprehensive Cancer CenterRecruitingAnatomic Stage I Breast Cancer AJCC v8 | Anatomic Stage IA Breast Cancer AJCC v8 | Anatomic Stage IB Breast Cancer AJCC v8 | Anatomic Stage II Breast Cancer AJCC v8 | Anatomic Stage IIA Breast Cancer AJCC v8 | Anatomic Stage IIB Breast Cancer AJCC v8 | Anatomic Stage III Breast Cancer AJCC v8 | Anatomic... and other conditionsUnited States
-
Ohio State University Comprehensive Cancer CenterNational Cancer Institute (NCI)WithdrawnAnatomic Stage I Breast Cancer AJCC v8 | Anatomic Stage IA Breast Cancer AJCC v8 | Anatomic Stage IB Breast Cancer AJCC v8 | Anatomic Stage II Breast Cancer AJCC v8 | Anatomic Stage IIA Breast Cancer AJCC v8 | Anatomic Stage IIB Breast Cancer AJCC v8 | Anatomic Stage III Breast Cancer AJCC v8 | Anatomic... and other conditions
-
Ohio State University Comprehensive Cancer CenterNational Cancer Institute (NCI)RecruitingAnatomic Stage IA Breast Cancer AJCC v8 | Anatomic Stage IB Breast Cancer AJCC v8 | Anatomic Stage II Breast Cancer AJCC v8 | Anatomic Stage IIA Breast Cancer AJCC v8 | Anatomic Stage IIB Breast Cancer AJCC v8 | Anatomic Stage III Breast Cancer AJCC v8 | Anatomic Stage IIIA Breast Cancer AJCC v8 | Anatomic Stage IIIB Breast Cancer AJCC... and other conditionsUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)CompletedAnatomic Stage II Breast Cancer AJCC v8 | Anatomic Stage IIA Breast Cancer AJCC v8 | Anatomic Stage IIB Breast Cancer AJCC v8 | Anatomic Stage III Breast Cancer AJCC v8 | Anatomic Stage IIIA Breast Cancer AJCC v8 | Anatomic Stage IIIB Breast Cancer AJCC v8 | Anatomic Stage IIIC Breast Cancer AJCC... and other conditionsUnited States
-
Mayo ClinicNational Cancer Institute (NCI)Active, not recruitingAnatomic Stage I Breast Cancer AJCC v8 | Anatomic Stage IA Breast Cancer AJCC v8 | Anatomic Stage IB Breast Cancer AJCC v8 | Anatomic Stage II Breast Cancer AJCC v8 | Anatomic Stage IIA Breast Cancer AJCC v8 | Anatomic Stage IIB Breast Cancer AJCC v8 | Anatomic Stage III Breast Cancer AJCC v8 | Anatomic... and other conditionsUnited States
-
M.D. Anderson Cancer CenterActive, not recruitingAnatomic Stage I Breast Cancer AJCC v8 | Anatomic Stage IA Breast Cancer AJCC v8 | Anatomic Stage IB Breast Cancer AJCC v8 | Anatomic Stage II Breast Cancer AJCC v8 | Anatomic Stage IIA Breast Cancer AJCC v8 | Anatomic Stage IIB Breast Cancer AJCC v8 | Anatomic Stage III Breast Cancer AJCC v8 | Anatomic... and other conditionsUnited States
Clinical Trials on Magnetic Resonance Imaging
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)CompletedHematopoietic and Lymphoid Cell Neoplasm | Malignant Solid NeoplasmUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Recruiting
-
M.D. Anderson Cancer CenterActive, not recruitingProstate Adenocarcinoma | Prostate CarcinomaUnited States
-
Wake Forest University Health SciencesNational Cancer Institute (NCI)CompletedStage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIA Breast Cancer | Stage IIB Breast Cancer | Stage IIIC Breast Cancer | Healthy SubjectUnited States
-
Stanford UniversityTerminatedLaryngeal Neoplasms | Head and Neck Cancers | Larynx CancerUnited States
-
Vanderbilt-Ingram Cancer CenterNational Cancer Institute (NCI)CompletedBreast CancerUnited States
-
OHSU Knight Cancer InstituteOregon Health and Science UniversityRecruitingIntracranial NeoplasmUnited States
-
University of California, San FranciscoTerminatedAnatomic Stage I Breast Cancer AJCC v8 | Anatomic Stage IA Breast Cancer AJCC v8 | Anatomic Stage IB Breast Cancer AJCC v8 | Anatomic Stage II Breast Cancer AJCC v8 | Anatomic Stage IIA Breast Cancer AJCC v8 | Anatomic Stage IIB Breast Cancer AJCC v8 | Anatomic Stage III Breast Cancer AJCC v8 | Anatomic... and other conditionsUnited States
-
Mayo ClinicNational Cancer Institute (NCI)RecruitingBreast Cancer | Breast Neoplasms | Anatomic Stage I Breast Cancer AJCC v8 | Anatomic Stage II Breast Cancer AJCC v8 | Anatomic Stage IIIA Breast Cancer AJCC v8 | Cancer-related Cognitive DysfunctionUnited States
-
Abramson Cancer Center of the University of PennsylvaniaCompletedBrain TumorUnited States