Pembrolizumab and Radiation for Triple Negative Breast Cancer

(P-RAD(+)TN-DCT Trial)

Overseen By Emily L Schworer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: UNC Lineberger Comprehensive Cancer Center

Must be taking: Neoadjuvant chemo-immunotherapy

Disqualifiers: Active infection, Pregnant, Prior breast cancer, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the optimal radiation dose to use with pembrolizumab, a cancer-fighting drug, for individuals with triple negative breast cancer, which lacks certain common receptors. The goal is to identify whether a low or high radiation dose best enhances the immune system's ability to combat the cancer. Suitable candidates for this trial have operable, lymph node-positive, triple negative breast cancer and plan to undergo standard chemotherapy and pembrolizumab treatment. Participants will receive either a low or high radiation dose, followed by chemotherapy and surgery. The trial aims to determine how to effectively combine radiation with pembrolizumab for improved outcomes. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to advancements in cancer therapy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that pembrolizumab, a drug used in this trial, is part of the standard treatment for early-stage triple-negative breast cancer. Studies have found that when combined with chemotherapy, it achieves a 5-year survival rate of about 86%. However, serious immune-related side effects have been reported, so discussing these with a doctor is crucial.

For radiation treatments, the goal is to find the right dose. Other studies have generally shown that low-dose radiation is well-tolerated, with some patients experiencing moderate skin changes. High-dose radiation has been linked to a lower chance of cancer recurrence but also causes more skin-related side effects. These findings highlight the need to carefully weigh the benefits and risks. A detailed conversation with a healthcare provider is essential to understand how these options might work. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for triple negative breast cancer involve chemotherapy, which targets rapidly dividing cells but can also affect healthy cells. Pembrolizumab is unique because it is an immunotherapy drug that works by blocking a protein called PD-1, boosting the immune system to attack cancer cells more effectively. Researchers are excited about combining pembrolizumab with radiation therapy because the radiation can increase the visibility of cancer cells to the immune system, potentially enhancing the effectiveness of pembrolizumab. This combination might offer a more targeted approach with the potential for fewer side effects compared to traditional chemotherapy.

What evidence suggests that this trial's treatments could be effective for triple negative breast cancer?

Research shows that combining pembrolizumab with radiation therapy may be promising for treating triple negative breast cancer (TNBC). Studies have found that this combination can lead to more patients having no signs of cancer in their breast and lymph nodes after treatment. For example, one study reported that 34.6% of patients achieved this result with pembrolizumab as part of their treatment. In this trial, participants will receive either a low-dose or high-dose radiation therapy boost. Radiation therapy plays a crucial role in TNBC treatment, with new techniques improving accuracy and possibly reducing the chance of cancer returning. The extra dose of radiation being tested has been linked to fewer cases of cancer recurrence in the same area. These findings suggest that using pembrolizumab and radiation together could effectively treat TNBC. ^{1 3 6 7 8}

Who Is on the Research Team?

Dana Casey, MD

Principal Investigator

UNC Lineberger Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for men and women with operable, lymph node-positive, triple negative breast cancer who can undergo standard chemo-immunotherapy. Participants must have available tissue biopsies or agree to baseline research biopsies of the primary tumor and metastatic lymph node.

Inclusion Criteria

I have signed the consent form and agree to share my health information for the study.

I am 18 years old or older.

I am fully active or able to carry out light work.

Exclusion Criteria

I have had breast cancer or another cancer that has worsened or needed treatment in the last 5 years.

Pregnant or breastfeeding

I am currently being treated for an infection with medication.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Phase

Participants receive pembrolizumab and radiation therapy, followed by standard-of-care neoadjuvant chemotherapy

24 weeks

Multiple visits for treatment and biopsies

Surgical Resection

Participants undergo standard of care surgical resection of the breast and axillary lymph nodes

1 week

1 visit for surgery

Adjuvant Phase

Participants receive standard of care adjuvant systemic therapy and radiotherapy if indicated

Varies based on individual treatment plans

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up every 6 months for 3 years

3 years

Biannual visits

What Are the Treatments Tested in This Trial?

Interventions

• High Dose Neoadjuvant Boost
• Low Dose Neoadjuvant Boost
• Pembrolizumab

Trial Overview

The study tests two different doses of radiation therapy (low dose: 9Gy; high dose: 24Gy) combined with Pembrolizumab in patients with triple negative breast cancer. Patients are randomly assigned to one of the radiation doses and all receive chemotherapy and immunotherapy.

How Is the Trial Designed?

Group I: ARM 2 Experimental Treatment 2 Interventions

Participants will receive a high dose radiation therapy boost in 3 fractions (8Gy x 3 fraction = 24Gy total).

Group II: ARM 1 Experimental Treatment 2 Interventions

Participants will receive a low dose radiation therapy boost in 3 fractions (3Gy x 3 fraction = 9Gy total).

Who Is Running the Clinical Trial?

UNC Lineberger Comprehensive Cancer Center

Lead Sponsor

Trials

377

Recruited

95,900+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11433471/

Treatment Outcomes after Postoperative Radiotherapy in ...

After neoadjuvant chemotherapy was performed in 130 patients, pathological complete remission (pCR) was reported in 11 patients (8.4%); 56 ...

2.

ascopost.com

ascopost.com/issues/november-10-2024/neoadjuvant-therapy-yields-notable-outcomes-in-triple-negative-breast-cancer/

Neoadjuvant Therapy Yields Notable Outcomes in Triple- ...

However, 18.1% were undertreated and 61.2% were overtreated, with no survival benefit for node-negative patients. The authors emphasized the ...

3.

sciencedirect.com

sciencedirect.com/science/article/pii/S1130634324000503

Effectiveness and safety of neoadjuvant therapy in triple ...

In the overall population, 27 patients (n = 78; 34.6%) achieved pathological complete response in the breast and axillary lymph nodes, and 31 (n = 73; 42.5%) ...

4.

cancertreatmentreviews.com

cancertreatmentreviews.com/article/S0305-7372(25)00061-1/fulltext

Enhancing radiotherapy techniques for Triple-Negative ...

Optimizing radiotherapy techniques and radiosensitization drugs can lead to more effective and personalized TNBC treatments, improving patient survival and ...

5.

pcm.amegroups.org

pcm.amegroups.org/article/view/6540/html

Role of radiation therapy in triple negative breast cancer

After a median FU of 38 months, it showed that 5y OS was higher in the group of patients who received adjuvant radiotherapy in the order of 77.2% compared to ...

6.

esmorwd.org

esmorwd.org/article/S2949-8201(24)00039-0/fulltext

Real-world safety and effectiveness of neoadjuvant ...

Treatment discontinuation rate due to adverse events (AEs) in the neoadjuvant phase was 35%. Half of the patients (50%) required dose reductions ...

7.

nature.com

nature.com/articles/s41523-022-00457-3

Patient-reported outcomes from a randomized trial of ...

These patient-reported data inform clinical benefit and decision-making for adding atezolizumab to neoadjuvant chemotherapy in early-stage TNBC.

8.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10068257/

The role of the radiation therapy breast boost in the 2020s - PMC

The boost dose reduced the 5-year local recurrence rate from 11.6% to 6.8% in case of negative margins and from 50.8% to 8.3% in case of close/ ...