search
Back to results

Rintatolimod, Celecoxib and Interferon Alpha 2b With Pembrolizumab For the Treatment of Patients With Metastatic or Unresectable Triple Negative Breast Cancer

Primary Purpose

Anatomic Stage IV Breast Cancer AJCC v8, Metastatic Triple-Negative Breast Carcinoma, Unresectable Triple-Negative Breast Carcinoma

Status
Not yet recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Biopsy
Biospecimen Collection
Celecoxib
Computed Tomography
Interferon Alpha-2
Magnetic Resonance Imaging
Pembrolizumab
Rintatolimod
Sponsored by
Roswell Park Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Anatomic Stage IV Breast Cancer AJCC v8

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 on prior therapy 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

Sites / Locations

  • Roswell Park Cancer Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Cohort I (CKM, pembrolizumab)

Cohort II (CMK, early pembrolizumab)

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Incidence of adverse events
The dose limiting toxicities will be summarized by cohort using frequencies and relative frequencies.

Secondary Outcome Measures

Progression-free survival
Will be summarized using standard Kaplan-Meier methods, with estimates of the median survival obtained with 90% confidence intervals.
Overall response rate
Evaluated using Immune Modulated Response Evaluation Criteria in Solid Tumors. Will be summarized using frequencies and relative frequencies, and obtained with 90% confidence intervals.
Overall survival
Will be summarized using standard Kaplan-Meier methods, with estimates of the median survival obtained with 90% confidence intervals.
Disease control rate
Will be summarized using frequencies and relative frequencies and obtained with 90% confidence intervals.

Full Information

First Posted
February 23, 2023
Last Updated
August 31, 2023
Sponsor
Roswell Park Cancer Institute
Collaborators
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT05756166
Brief Title
Rintatolimod, Celecoxib and Interferon Alpha 2b With Pembrolizumab For the Treatment of Patients With Metastatic or Unresectable Triple Negative Breast Cancer
Official Title
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 Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
September 30, 2023 (Anticipated)
Primary Completion Date
June 30, 2025 (Anticipated)
Study Completion Date
June 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Roswell Park Cancer Institute
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anatomic Stage IV Breast Cancer AJCC v8, Metastatic Triple-Negative Breast Carcinoma, Unresectable Triple-Negative Breast Carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
12 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cohort I (CKM, pembrolizumab)
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort II (CMK, early pembrolizumab)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Procedure
Intervention Name(s)
Biopsy
Other Intervention Name(s)
BIOPSY_TYPE, Bx
Intervention Description
Undergo tumor biopsy
Intervention Type
Procedure
Intervention Name(s)
Biospecimen Collection
Other Intervention Name(s)
Biological Sample Collection, Biospecimen Collected, Specimen Collection
Intervention Description
Undergo blood sample collection
Intervention Type
Drug
Intervention Name(s)
Celecoxib
Other Intervention Name(s)
Benzenesulfonamide, 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-, Celebrex, SC-58635, YM 177
Intervention Description
Given PO
Intervention Type
Procedure
Intervention Name(s)
Computed Tomography
Other Intervention Name(s)
CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized Tomography, CT, CT Scan, tomography
Intervention Description
Undergo CT scan
Intervention Type
Biological
Intervention Name(s)
Interferon Alpha-2
Other Intervention Name(s)
Alpha-2-Interferon, Alpha-2a Interferon, IFN-Alpha-2, IFN-AlphaA, IFNA2, IFNA2 Protein, Interferon Alpha 2, Interferon Alpha 2a, Interferon Alpha 2b, Interferon Alpha A, Interferon Alpha-A, LeIF A
Intervention Description
Given IV
Intervention Type
Procedure
Intervention Name(s)
Magnetic Resonance Imaging
Other Intervention Name(s)
Magnetic Resonance, Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging
Intervention Description
Undergo MRI
Intervention Type
Biological
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
Keytruda, Lambrolizumab, MK-3475, SCH 900475
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Rintatolimod
Other Intervention Name(s)
Ampligen, Atvogen
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Incidence of adverse events
Description
The dose limiting toxicities will be summarized by cohort using frequencies and relative frequencies.
Time Frame
Up to 2 years
Secondary Outcome Measure Information:
Title
Progression-free survival
Description
Will be summarized using standard Kaplan-Meier methods, with estimates of the median survival obtained with 90% confidence intervals.
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
Title
Overall response rate
Description
Evaluated using Immune Modulated Response Evaluation Criteria in Solid Tumors. Will be summarized using frequencies and relative frequencies, and obtained with 90% confidence intervals.
Time Frame
From the start of study treatment until end of treatment or disease progression/recurrence, assessed up to 2 years
Title
Overall survival
Description
Will be summarized using standard Kaplan-Meier methods, with estimates of the median survival obtained with 90% confidence intervals.
Time Frame
From the start of post-CKM therapy until death due to any cause or last follow up, assessed up to 2 years
Title
Disease control rate
Description
Will be summarized using frequencies and relative frequencies and obtained with 90% confidence intervals.
Time Frame
Up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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 on prior therapy 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shipra Gandhi
Organizational Affiliation
Roswell Park Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shipra Gandhi
Phone
716-845-1486
Email
Shipra.Gandhi@RoswellPark.org
First Name & Middle Initial & Last Name & Degree
Shipra Gandhi

12. IPD Sharing Statement

Learn more about this trial

Rintatolimod, Celecoxib and Interferon Alpha 2b With Pembrolizumab For the Treatment of Patients With Metastatic or Unresectable Triple Negative Breast Cancer

We'll reach out to this number within 24 hrs