Phase II Study of Docetaxel Chemotherapy With Pembrolizumab and Interleukin-12 Gene Therapy in Patients With Anthracycline- Refractory Triple Negative Breast Cancer (INTEGRAL)
Overview
- Phase
- Phase 2
- Intervention
- Docetaxel
- Conditions
- Triple Negative Breast Cancer
- Sponsor
- The Methodist Hospital Research Institute
- Enrollment
- 8
- Locations
- 1
- Primary Endpoint
- Pathological Complete Response (pCR) Rate of Docetaxel Chemotherapy and Pembrolizumab Plus IL-12 Gene Therapy
- Status
- Terminated
- Last Updated
- 3 months ago
Overview
Brief Summary
The purpose of this research study is to test the safety and effectiveness of docetaxel chemotherapy and pembrolizumab plus adenoviral-mediated interleukin-12 (ADV/IL-12) gene therapy in patients with anthracycline-refractory, triple negative breast cancer (TNBC).
Detailed Description
The purpose of this study is to learn how triple negative breast cancer (TNBC) responds to the use of chemotherapy, pembrolizumab, and gene therapy together in patients who have previously not responded to treatment. We will also look at the effects, good or bad, the study therapy has on you and your TNBC. Chemotherapy given before breast cancer surgery is called neoadjuvant chemotherapy. It shrinks the breast tumor, so it is easier to remove during surgery. Docetaxel is often used for the neoadjuvant treatment of breast cancer. Unfortunately, a lot of breast tumors do not shrink with docetaxel chemotherapy treatment. Docetaxel chemotherapy is standard care for TNBC. Pembrolizumab is a type of treatment that stimulates your own immune system to attack cancer cells. Your immune system is normally your body's first defense against threats like cancer. However, sometimes cancer cells produce signals that prevent the immune system from detecting and killing them. Pembrolizumab helps your immune system so it can detect and attack cancer cells. Chemotherapy plus pembrolizumab has been shown to be better than chemotherapy alone for shrinking breast tumors before surgery. To help increase the tumor-shrinking activity of docetaxel chemotherapy and pembrolizumab, you will be given more treatments, Interleukin-12 (IL-12) gene therapy This treatments will be used to boost the cancer-fighting ability of your immune system. Thus, the use of IL-12 gene therapy with docetaxel chemotherapy and pembrolizumab may make your immune system work harder to shrink your tumor. IL-12 is a substance that is normally made by certain immune cells in the body. IL-12 stimulates T cells, a special type of immune cell in the blood, to respond to threats to your body like cancer. After you finish the study treatment, you will have your breast cancer surgery.
Investigators
Polly A. Niravath, MD
Professor of Medicine in Oncology, Academic Institute
The Methodist Hospital Research Institute
Eligibility Criteria
Inclusion Criteria
- •Patients are eligible to be included in the trial only if all of the following criteria apply:
- •The patient (or legally acceptable representative if applicable) provides written informed consent for the trial.
- •Female ≥ 18 years of age on the day of informed consent signing.
- •Histologically confirmed triple negative breast cancer is defined as estrogen receptor (ER), progesterone receptor (PR), and HER2 negative. ER/PR negativity is defined as \<10% IHC staining of any intensity.
- •HER2 negativity is defined as the following per the 2018 American Society of Clinical Oncology and College of American Pathologists guidelines.
- •4\. Refractory to standard neoadjuvant anthracycline-containing chemotherapy regimen, demonstrated on MRI.
- •5\. Bilateral breast cancers that individually meet eligibility criteria are allowed.
- •6\. Prior immunotherapy treatment allowed.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Adequate organ function as defined in Table
Exclusion Criteria
- •History of poorly controlled hypertension (defined as systolic blood pressure \>150 mmHg). Patients whose hypertension has been well controlled on the same treatment for 1 year prior to Cycle 1, Day 1 are eligible. Only patients on single-agent antihypertensive therapy are allowed.
- •History of New York Heart Association class III or greater cardiac disease.
- •History of myocardial infarction, stroke, ventricular arrhythmia, or greater than first-degree conduction defect within the past 12 months.
- •History of congenital QT prolongation.
- •Absolute corrected QT interval of \>480 msec in the presence of potassium \>4.0 mEq/L and magnesium \>1.8 mg/dL.
- •Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to trial treatment administration.
- •NOTE: Patients who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
- •8\. Concurrent use of any complementary or alternative medicines.
- •Concurrent use of inhibitors or inducers of cytochrome P450 (CYP)3A4 and CYP2D6
- •Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (dose exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to trial treatment administration.
Arms & Interventions
Experimental
docetaxel chemotherapy and pembrolizumab plus IL-12 gene therapy.
Intervention: Docetaxel
Experimental
docetaxel chemotherapy and pembrolizumab plus IL-12 gene therapy.
Intervention: Pembrolizumab
Experimental
docetaxel chemotherapy and pembrolizumab plus IL-12 gene therapy.
Intervention: IL-12 gene therapy
Outcomes
Primary Outcomes
Pathological Complete Response (pCR) Rate of Docetaxel Chemotherapy and Pembrolizumab Plus IL-12 Gene Therapy
Time Frame: 18 weeks
To determine the pCR rate of docetaxel chemotherapy and pembrolizumab plus IL-12 gene therapy in patients with TNBC per RECIST v1.1 assessed by CT Scan or MRI. CR: Disappearance of all target lesions. PR: at least a 30% decrease in the sum of the longest diameter of target lesions, using the baseline sum longest diameter as a reference. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, using the smallest sum longest diameter as a reference. PD: At least a greater than or equal to 20% increase in the sum of the longest dimensions of the target lesions taking as a reference the smallest sum of the longest dimensions recorded since the treatment started, or the appearance of one or more new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Clinical PD: Patients who in the opinion of the treating PI have clinical evidence of PD may be classified as having PD
Secondary Outcomes
- Number of Participants With Treatment-related Adverse Events(18 weeks)