Immunotherapy + Radiation for Hormone-Sensitive Breast Cancer
(CBCV Trial)
Recruiting in Palo Alto (17 mi)
+4 other locations
Age: 18+
Sex: Female
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Weill Medical College of Cornell University
Must be taking: Hormonal therapy
Must not be taking: Chemotherapy, Endocrine therapy, HER2 therapy, Immunotherapy
Disqualifiers: Connective tissue disorders, Autoimmune disease, Immunodeficiency, others
Stay on your current meds
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Approved in 2 jurisdictions
Trial Summary
What is the purpose of this trial?This trial tests different treatments in post-menopausal women with a specific type of breast cancer. The goal is to find the best way to lower hormones, kill cancer cells, or boost the immune system to fight the disease. One of the treatments being tested is a medication used for treating postmenopausal women with hormone-sensitive advanced breast cancer.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are currently using systemic chemotherapy, endocrine therapy, or HER2-neu targeted therapy.
What data supports the effectiveness of this treatment for hormone-sensitive breast cancer?
Research suggests that combining radiation therapy with immunotherapy, like PD-1 blockade, can enhance the immune system's ability to fight cancer, as seen in studies with other types of cancer. This combination has shown promise in making tumors more responsive to treatment by activating immune cells and reducing suppressive cells in the tumor environment.
12345Is hypofractionated radiation therapy safe for breast cancer patients?
Research shows that hypofractionated radiation therapy (a type of radiation treatment given in larger doses over fewer sessions) is generally safe and effective for breast cancer patients, with similar safety profiles to traditional radiation therapy. However, there are still concerns about potential side effects and local recurrence, especially in younger women.
25678What makes the treatment of Immunotherapy + Focal Radiation therapy unique for hormone-sensitive breast cancer?
This treatment is unique because it combines focal hypofractionated radiation therapy, which delivers high doses of radiation in fewer sessions, with immunotherapy to potentially enhance the immune system's ability to attack cancer cells. This combination may lead to both local and distant (abscopal) effects, where the immune response is activated not only at the site of radiation but also in other parts of the body.
123910Eligibility Criteria
Post-menopausal women over 18 with stage I-III HR+HER2- breast cancer, who can sign consent and have good performance status (ECOG 0-1). They must have adequate organ function and no prior treatments with certain immune drugs, severe allergies to pembrolizumab, or immunosuppressive therapies. Excluded are those with active infections, certain viral diseases like HIV or hepatitis B/C, recent live vaccines, autoimmune diseases requiring treatment in the past 2 years, other cancers within 3 years.Inclusion Criteria
My breast cancer is ER positive, may or may not be PR positive, and is HER2 negative.
My breast cancer is between stage I (larger than 1.5cm if no lymph node involvement) and III.
Patient needs to be able to understand and demonstrate willingness to sign a written informed consent document
+3 more
Exclusion Criteria
Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
I haven't needed systemic treatment for an autoimmune disease in the last 2 years.
I have an active tuberculosis infection.
+15 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive 4 months of standard neoadjuvant hormonal therapy with letrozole, with additional treatments depending on the assigned arm, including focal hypo-fractionated radiation therapy and potentially pembrolizumab or FLT3L.
16 weeks
Multiple visits for treatment administration
Surgery
Breast surgery is performed at the end of the treatment phase.
1 week
1 visit (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment, including a one-month follow-up period after surgery.
4 weeks
1-2 visits (in-person)
Participant Groups
The trial is testing focal radiation therapy alone or combined with immunotherapy drugs Pembrolizumab and CDX-301 on patients already receiving standard hormonal therapy. Participants are randomly assigned to one of four groups at five US academic institutions.
4Treatment groups
Active Control
Group I: ARM 3Active Control2 Interventions
Ftl-3 ligand, self-administered by subcutaneous injections at week 1, daily, for 5 consecutive days + Focal hypo-fractionated radiation therapy - 8 Gy x 3 fractions starting day 8, (every other day (M/W/F or W/F/M or F/M/W).
Group II: ARM 2Active Control2 Interventions
Focal hypo-fractionated radiation therapy - 8 Gy x 3 fractions starting day 8, every other day (M/W/F or W/F/M or F/M/W). + Pembrolizumab, on day 12 (last day of radiotherapy), infused over 200mg IV over 30 minutes and then repeated every 3 weeks until disease progression or unacceptable toxicity.
Group III: ARM 4Active Control3 Interventions
Ftl-3 ligand, self administered subcutaneous injections at day 1 for 5 consecutive days+ Focal hypo-fractionated Radiation therapy starting day 8, - 8 Gy x 3 fractions, every other day (M/W/F or W/F/M or F/M/W). + Pembrolizumab, on day 12 (last day of radiotherapy), 200mg IV infused over 30 minutes then repeated every 3 weeks until disease progression or unacceptable toxicity.
Group IV: ARM 1Active Control1 Intervention
Focal hypo-fractionated radiation therapy 8 Gy x 3 fractions, starting day 8, every other day (M/W/F or W/F/M or F/M/W).
Focal Radiation therapy is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Radiation Therapy for:
- Breast cancer
- Various types of cancer
🇪🇺 Approved in European Union as Radiation Therapy for:
- Breast cancer
- Various types of cancer
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Weill Cornell Medicine New York Presbyterian HospitalNew York, NY
Brooklyn Methodist Hospital - NewYork PresbyterianNew York, NY
Houston Methodist Cancer CenterHouston, TX
New York Presbyterian Hospital - QueensNew York, NY
More Trial Locations
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Who Is Running the Clinical Trial?
Weill Medical College of Cornell UniversityLead Sponsor
Merck Sharp & Dohme LLCIndustry Sponsor
Celldex TherapeuticsIndustry Sponsor
United States Department of DefenseCollaborator
References
Definitive chemoradiation alters the immunologic landscape and immune checkpoints in head and neck cancer. [2022]Preclinical and clinical studies suggest potential synergy between high dose per fraction focal radiation and immunotherapy. However, conventionally fractionated radiation regimens in combination with concurrent chemotherapy are more commonly administered to patients as definitive treatment and may have both immune-stimulating and -suppressive effects.
Accelerated hypofractionated whole-breast irradiation with concomitant daily boost in early breast cancer. [2022]The aim of this study is to evaluate the feasibility and the related toxicity of hypofractionated whole-breast irradiation with a concomitant daily boost in early breast cancer women not eligible for accelerated partial-breast irradiation.
Abscopal Effects With Hypofractionated Schedules Extending Into the Effector Phase of the Tumor-Specific T-Cell Response. [2019]Hypofractionated radiation therapy (hRT) combined with immune checkpoint blockade can induce T-cell-mediated local and abscopal antitumor effects. We had previously observed peak levels of tumor-infiltrating lymphocytes (TILs) between days 5 and 8 after hRT. Because TILs are regarded as radiosensitive, hRT schedules extending into this period might be less immunogenic, prompting us to compare clinically relevant, short and extended schedules with equivalent biologically effective doses combined with anti-programmed cell death 1 (PD1) antibody treatment.
Converging focal radiation and immunotherapy in a preclinical model of triple negative breast cancer: contribution of VISTA blockade. [2021]Antibodies targeting the co-inhibitory receptor programmed cell death 1 (PDCD1, best known as PD-1) or its main ligand CD274 (best known as PD-L1) have shown some activity in patients with metastatic triple-negative breast cancer (TNBC), especially in a recent Phase III clinical trial combining PD-L1 blockade with taxane-based chemotherapy. Despite these encouraging findings, however, most patients with TNBC fail to derive significant benefits from PD-L1 blockade, calling for the identification of novel therapeutic approaches. Here, we used the 4T1 murine mammary cancer model of metastatic and immune-resistant TNBC to test whether focal radiation therapy (RT), a powerful inducer of immunogenic cell death, in combination with various immunotherapeutic strategies can overcome resistance to immune checkpoint blockade. Our results suggest that focal RT enhances the therapeutic effects of PD-1 blockade against primary 4T1 tumors and their metastases. Similarly, the efficacy of an antibody specific for V-set immunoregulatory receptor (VSIR, another co-inhibitory receptor best known as VISTA) was enhanced by focal RT. Administration of cyclophosphamide plus RT and dual PD-1/VISTA blockade had superior therapeutic effects, which were associated with activation of tumor-infiltrating CD8+ T cells and depletion of intratumoral granulocytic myeloid-derived suppressor cells (MDSCs). Overall, these results demonstrate that RT can sensitize immunorefractory tumors to VISTA or PD-1 blockade, that this effect is enhanced by the addition of cyclophosphamide and suggest that a multipronged immunotherapeutic approach may also be required to increase the incidence of durable responses in patients with TNBC.
Hypofractionated Whole-Breast Irradiation in Women Less Than 50 Years Old Treated on 4 Prospective Protocols. [2019]Hypofractionated whole-breast radiation therapy (RT) has proved to be equivalent to conventionally fractionated RT in multiple randomized trials. There is controversy regarding its use in younger women because of their underrepresentation in trials and the concern for late toxicity. We evaluated disease control and cosmetic outcomes in patients aged
Hypofractionated radiation treatment in early breast cancer: Results in a New Zealand setting. [2018]High-quality evidence supports that hypofractionated radiation treatment (HFRT) is as effective and safe in early breast cancer as conventionally fractionated radiation treatment. HFRT with fewer treatments has potential benefits for both patients and radiation departments. Despite this, concerns about local control and toxicity with HFRT persist, such that many eligible patients do not receive HFRT. The local recurrence rates and acute toxicity after HFRT was analyzed in our center in Christchurch, New Zealand.
Differences in the Acute Toxic Effects of Breast Radiotherapy by Fractionation Schedule: Comparative Analysis of Physician-Assessed and Patient-Reported Outcomes in a Large Multicenter Cohort. [2022]Randomized trials have established the long-term safety and efficacy of hypofractionated whole-breast radiotherapy, but little is known about the acute toxic effects experienced by patients treated with hypofractionation as compared with conventional fractionation, particularly in real-world settings and from the patient's own perspective.
Hypofractionated radiotherapy for breast cancer patients treated by breast-conserving surgery: short-term morbidity and preliminary results. [2018]Hypofractionated adjuvant radiotherapy (RT) in breast cancer patients treated by conservative surgery has been increasingly used in recent years. We present our experience regarding tolerance/acute toxicity of a hypofractionated RT schedule.
Fostering efficacy of anti-PD-1-treatment: Nivolumab plus radiotherapy in advanced non-small cell lung cancer - study protocol of the FORCE trial. [2020]Hypofractionated palliative radiotherapy for metastatic lung cancer patients is frequently used in order to ease pain, to increase bone stability, to treat local mass effects, or to prolong progression-free survival at critical sites. Recently introduced, immunotherapy for patients with non-squamous non-small cell lung carcinoma (NSCLC) has significantly improved outcome in this cohort. Preclinical and early clinical data suggest that the combination of photon radiation with programmed death-1 (PD-1) targeting immunotherapies may promote a strong and durable immune response against tumor manifestations both within and beyond radiation targets.
Combining spatially fractionated radiation therapy (SFRT) and immunotherapy opens new rays of hope for enhancing therapeutic ratio. [2023]Spatially Fractionated Radiation Therapy (SFRT) is a form of radiotherapy that delivers a single large dose of radiation within the target volume in a heterogeneous pattern with regions of peak dosage and regions of under dosage. SFRT types can be defined by how the heterogeneous pattern of radiation is obtained. Immune checkpoint inhibitors (ICIs) have been approved for various malignant tumors and are widely used to treat patients with metastatic cancer. The efficacy of ICI monotherapy is limited due to the "cold" tumor microenvironment. Fractionated radiotherapy can achieve higher doses per fraction to the target tumor, and induce immune activation (immodulate tumor immunogenicity and microenvironment). Therefore, coupling ICI therapy and fractionated radiation therapy could significantly improve the outcome of metastatic cancer. This review focuses on both preclinical and clinical studies that use a combination of radiotherapy and ICI therapy in cancer.