Chemokine Modulation Therapy and Pembrolizumab in Treating Participants With Metastatic Triple-Negative Breast Cancer
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03599453|
Recruitment Status : Recruiting
First Posted : July 26, 2018
Last Update Posted : January 2, 2020
|Condition or disease||Intervention/treatment||Phase|
|Triple -Negative Breast Cancer Estrogen Receptor Negative HER2/Neu Negative Anatomic Stage IV Breast Cancer AJCC Progesterone Receptor Negative||Procedure: Biopsy Procedure: Chemokine Modulation Therapy Drug: Celecoxib Biological: Recombinant Interferon Alfa-2b Drug: Rintatolimod Biological: Pembrolizumab||Early Phase 1|
-To evaluate the increase of CD8+ infiltration into tumor microenvironment after pre-treatment CKM regime
- To evaluate the overall response rate (ORR) to the combination therapy per RECIST v1.1
- To evaluate the efficacy of the chemokine modulation (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 progression-free survival (PFS), overall survival (OS), and disease control rate (DCR).
- To evaluate the safety profile of CKM regimen given as pre-treatment to pembrolizumab therapy in metastatic breast cancer patients using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
- Examine the immune analysis profile of CKM and pembrolizumab combination.
- 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.
- Correlate PD-L1 expression within both neoplastic and nonneoplastic stromal elements of the tumor microenvironment to PFS, OS, ORR and adverse events (AEs).
- Correlate Immune Panel results with ORR, PFS, OS and AEs.
- Comparison of response assessment criteria for a prospective analysis
Participants undergo pre-treatment biopsy. Participants then undergo chemokine modulation therapy consisting of celecoxib orally (PO) twice daily (BID), recombinant interferon alfa-2b intravenously (IV) over 20 minutes, and rintatolimod IV over 30-60 minutes on days -11 to -9, and -4 to -2. Participants then undergo additional biopsy. Following biopsy and chemokine modulation therapy, participants receive pembrolizumab IV over 30 minutes on day 1. After completion of study treatment, participants are followed up for 90 days and then every 6 months for up to 2 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||6 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Pilot Open Label Clinical Trial Evaluating the Safety and Efficacy of Chemokine Modulation to Enhance the Effectiveness of Pembrolizumab in Patients With Metastatic Triple Negative Breast Cancer|
|Actual Study Start Date :||January 9, 2019|
|Estimated Primary Completion Date :||June 6, 2021|
|Estimated Study Completion Date :||July 6, 2022|
Experimental: Treatment (chemokine modulation therapy)
Participants undergo pre-treatment biopsy. Participants then undergo chemokine modulation therapy consisting of celecoxib PO BID, recombinant interferon alfa-2b IV over 20 minutes, and rintatolimod IV over 30-60 minutes on days -11 to -9, and -4 to -2. Participants then undergo additional biopsy. Following biopsy and chemokine modulation therapy, participants receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity.
Procedure: Chemokine Modulation Therapy
Undergo chemokine modulation therapy
Given by mouth
Other Name: Celebrex, YM 177, Benzenesulfonamide
Biological: Recombinant Interferon Alfa-2b
Other Name: Alfatronol, Glucoferon, Heberon Alfa, IFN alpha-2B, Interferon alfa 2b, Intron A, recombinant interferon alfa-2b, Recombinant Interferon Alfa-2b, Sch
Other Name: 38640-92-5, 616524, Ampligen, Ampligen, Atvogen, Poly(I).Poly(c12,U), Poly(Inosinic Acid) Poly(Cytidylic(12), Uridylic)Acid, RINTATOLIMOD, Rintatolimod
Other Name: Immunoglobulin G4,Keytruda, Lambrolizumab
- Overall response rate (ORR) as measured by immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) criteria 1.1 [ Time Frame: Up to 2 years ]Will be assessed using a Simon two-stage minimax design.
- Progression-free survival (PFS) as measured by irRECIST 1.1 criteria [ Time Frame: Up to 2 years ]Will be assessed using a Simon two-stage minimax design
- Overall survival (OS) as measured by irRECIST 1.1 criteria [ Time Frame: Up to 2 years ]
- Disease control rate (DCR) as measured by irRECIST 1.1 criteria [ Time Frame: Up to 2 years ]Will be assessed using a Simon two-stage minimax design
- Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 [ Time Frame: Up to 2 years ]Adverse events (AEs), serious AEs (SAEs), and toxicities will be summarized by attribution (overall and related/unrelated to treatment) and grade using frequencies and relative frequencies
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03599453
|Contact: Ask RPCIfirstname.lastname@example.org|
|United States, New York|
|Roswell Park Cancer Institute||Recruiting|
|Buffalo, New York, United States, 14263|
|Principal Investigator:||Shipra Gandhi, MD||Roswell Park Cancer Institute|