Radiation, Immunotherapy, and Chemotherapy for Metastatic Triple Negative Breast Cancer

Overseen By Manali Bhave, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Emory University

Must not be taking: Glucocorticoids, Immunosuppressives

Disqualifiers: CNS disease, Hypercalcemia, Autoimmune, others

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

Compensation: Varies

Number of Visits: 36

Duration: Up to 1 year

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of combining radiation, immunotherapy, and chemotherapy to treat PD-L1 positive metastatic triple negative breast cancer. The researchers aim to determine if this approach can halt the cancer's growth and spread by using high-dose radiation, pembrolizumab (a drug that boosts the immune system against cancer), and various chemotherapy options. Suitable candidates for this trial have this type of breast cancer that has metastasized and can undergo high-dose radiation. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, during the trial, you should not receive other cancer treatments except for specific ones like bisphosphonates or RANK-L inhibitors. It's best to discuss your current medications with the trial team.

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

Research has shown that the treatments tested in this trial have varying safety levels based on past studies.

The chemotherapy drugs carboplatin and gemcitabine often treat metastatic triple-negative breast cancer (mTNBC). They are usually well-tolerated, but some patients might experience side effects like low blood cell counts and nausea.

Paclitaxel and its version, nab-paclitaxel, are also common in cancer treatment. Nab-paclitaxel may cause fewer side effects than regular paclitaxel. Patients have reported side effects such as hair loss and low blood cell counts.

Pembrolizumab, an immunotherapy drug, has been extensively studied. It has shown promising results in helping breast cancer patients live longer. Some common side effects include tiredness and skin reactions, but it is generally considered safe.

High-dose radiation therapy is another part of this trial. Research indicates it is often well-tolerated, though some patients may feel tired and have skin irritation.

Overall, these treatments have been used in many situations and are considered safe for many patients. However, each person’s reaction can differ, so discussing possible side effects with healthcare providers is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment for metastatic triple-negative breast cancer because it combines high-dose radiation with pembrolizumab, an immunotherapy drug, and standard chemotherapy options. This approach is unique because it leverages the immune system's ability to fight cancer, potentially enhancing the effects of traditional chemotherapy. Pembrolizumab is a checkpoint inhibitor, which helps the immune system recognize and attack cancer cells more effectively. The integration of radiation therapy could heighten the immune response, potentially leading to better outcomes compared to standard treatments alone, which typically include chemotherapy without the added benefits of immunotherapy and radiation.

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

Studies have shown promising results for the treatments in this trial for metastatic triple negative breast cancer. Research indicates that pembrolizumab, which participants in this trial may receive, significantly improves survival rates when combined with chemotherapy compared to chemotherapy alone. Specifically, it reduces the risk of cancer progression by 35% and the risk of death by 27%. Participants may also receive nab-paclitaxel, another effective option, showing similar results to other treatments. Paclitaxel, another chemotherapy option in this trial, improves survival rates, with 39% of patients living for at least two years compared to other treatments. Alternatively, some participants may receive carboplatin and gemcitabine, which also show promise; studies suggest these drugs improve outcomes when used together for this type of cancer. High-dose radiation therapy, part of the treatment regimen in this trial, often kills cancer cells and shrinks tumors, benefiting many patients with similar conditions. ^{5 6 7 8 9}

Who Is on the Research Team?

Manali Bhave, MD

Principal Investigator

Emory University

Are You a Good Fit for This Trial?

This trial is for individuals with PD-L1 positive metastatic triple negative breast cancer. Participants should have cancer that has spread from the original site to other body parts. Specific eligibility criteria are not provided, but typically include factors like age, health status, and previous treatments.

Inclusion Criteria

I am eligible for radiotherapy, immunotherapy, and taxane chemotherapy.

My cancer is not driven by estrogen or progesterone.

AST, ALT ≤ 2.5 x ULN (≤ 5 x ULN for patients with liver metastases)

Exclusion Criteria

Severe, active co-morbidities

Conditions or abnormalities that may confound trial results

Known hypersensitivity to nab-paclitaxel or excipients

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Patients undergo radiation therapy once every other day for 3 doses

1 week

3 visits (in-person)

Treatment

Patients receive pembrolizumab and chemotherapy. Cycles repeat every 21 or 28 days depending on chemotherapy regimen

Up to 1 year

Multiple visits (in-person) every 21 or 28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

Every 12 weeks

Follow-up visits every 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Gemcitabine
• High Dose Radiation Therapy
• Paclitaxel
• Pembrolizumab

Trial Overview The study tests high dose radiation therapy combined with pembrolizumab (an immunotherapy drug) and chemotherapy drugs (paclitaxel or nab-paclitaxel or carboplatin and gemcitabine). The goal is to see if this combination can effectively kill tumor cells in patients with a specific type of advanced breast cancer.

How Is the Trial Designed?

Group I: Treatment (radiation, pembrolizumab, chemotherapy) Experimental Treatment 11 Interventions

Patients undergo radiation therapy once every other day for 3 doses. Beginning within 48 hours of their first dose of radiation therapy, patients receive standard of care pembrolizumab IV on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also receive 1 of 3 standard of care chemotherapy options: nab-paclitaxel IV on days 1, 8, and 15 of each cycle, or paclitaxel IV on days 1, 8, and 15 of each cycle, or carboplatin IV and gemcitabine IV on days 1 and 8 of each cycle. Cycles of nab-paclitaxel and paclitaxel repeat every 28 days and cycles of carboplatin and gemcitabine repeat every 21 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo a biopsy at baseline and 2 weeks after radiation therapy and also undergo CT scans, bone scans and blood sample collections throughout the trial.

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In the KEYNOTE-355 trial, patients with previously untreated metastatic triple-negative breast cancer (mTNBC) who received pembrolizumab combined with chemotherapy experienced a significant improvement in quality-adjusted survival, gaining an average of 3.7 months more time without symptoms or treatment toxicity compared to those receiving chemotherapy alone.

The benefits of pembrolizumab plus chemotherapy increased over time, with a 20% relative gain in quality-adjusted survival at a maximum follow-up of 52 months, indicating both efficacy and manageable safety in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Q-TWiST analysis of pembrolizumab combined with chemotherapy as first-line treatment of metastatic triple-negative breast cancer that expresses PD-L1. Huang, M., O'Shaughnessy, J., Haiderali, A., et al.[2023]

In the IMpassion130 trial, the combination of atezolizumab and nab-paclitaxel (A + nP) significantly improved progression-free survival in patients with metastatic triple-negative breast cancer (mTNBC) without negatively impacting their health-related quality of life (HRQoL).

Patient-reported outcomes showed no significant differences in HRQoL or functioning between the A + nP and placebo plus nab-paclitaxel groups, indicating that the treatment did not worsen symptoms like fatigue or nausea, thus maintaining patients' day-to-day functioning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes from the phase III IMpassion130 trial of atezolizumab plus nab-paclitaxel in metastatic triple-negative breast cancer. Adams, S., Diéras, V., Barrios, CH., et al.[2022]

In the phase III KEYNOTE-522 trial, pembrolizumab combined with chemotherapy showed increased effectiveness as a neoadjuvant treatment for triple-negative breast cancer, leading to a higher rate of pathologic complete response compared to chemotherapy alone.

This benefit was observed regardless of the PD-L1 expression levels in patients, suggesting that pembrolizumab may be a broadly effective option for this aggressive cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant Pembrolizumab Takes on TNBC. [2020]

In a phase 2 clinical trial involving 17 patients with metastatic triple-negative breast cancer, the combination of pembrolizumab and radiotherapy showed an overall response rate of 17.6%, with three patients achieving complete responses that lasted up to 108 weeks.

The treatment was found to be safe, with the most common side effects being mild dermatitis, and no treatment-related deaths or severe adverse events reported, indicating a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 2 clinical trial assessing the efficacy and safety of pembrolizumab and radiotherapy in patients with metastatic triple-negative breast cancer. Ho, AY., Barker, CA., Arnold, BB., et al.[2020]

Cisplatin and capecitabine combination therapy showed a response rate of 62.1% in 29 patients with metastatic triple negative breast cancer (TNBC) who had previously progressed after other treatments, indicating its efficacy as a subsequent treatment option.

The therapy was generally well-tolerated, with most side effects being mild to moderate, although some patients experienced significant toxicities such as neutropenia and leukocytopenia, highlighting the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of cisplatin plus capecitabine for patients with metastatic triple negative breast cancer progressing after anthracycline and taxane treatment]. Li, Q., Xu, B., Li, Q., et al.[2018]

In a phase 3 trial involving 902 patients with metastatic triple-negative breast cancer, the combination of atezolizumab and nab-paclitaxel showed a median overall survival of 21.0 months compared to 18.7 months with placebo, although this difference was not statistically significant in the overall population.

For patients with PD-L1 immune cell-positive tumors, atezolizumab plus nab-paclitaxel demonstrated a significant overall survival benefit, with a median survival of 25.0 months versus 18.0 months for placebo, highlighting its potential as an important treatment option for this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial. Schmid, P., Rugo, HS., Adams, S., et al.[2020]

Citations

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Chemotherapy of metastatic triple negative breast cancer Compared with other kinds of platinum, cisplatin-based regimens as the first-line chemotherapy showed better PFS (8.0 vs. 4.3 months, P = 0.03) and better ORR.

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Efficacy and Safety of First-line Carboplatin-paclitaxel and ... Results. Of 88 consecutive advanced TNBC patients receiving first-line carboplatin-based doublets, 56 (63.6%) received CP and 32 (36.4%) CG.

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Efficacy and Safety of First-line Carboplatin-paclitaxel and ... Of 88 consecutive advanced TNBC patients receiving first-line carboplatin-based doublets, 56 (63.6%) received CP and 32 (36.4%) CG. After ...

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Effect of Adjuvant Paclitaxel and Carboplatin on Survival in ... Results of this study suggest that a paclitaxel-plus-carboplatin regimen may be an alternative adjuvant chemotherapy choice for patients with operable triple- ...

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Combination therapy improves outcomes for advanced ... Combination therapy improves outcomes for advanced triple-negative breast cancer ... efficacy of carboplatin and everolimus in metastatic TNBC.

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nab-Paclitaxel plus carboplatin or gemcitabine versus ... The results of the tnAcity trial indicate that treatment with chemotherapy remains a viable first-line option for patients with metastatic triple-negative ...

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Efficacy and safety of BEBT-209, a primary CDK4 inhibitor ... Methods: This Phase II study evaluated BEBT-209 in combination with gemcitabine and carboplatin (GC) in patients with mTNBC. The cohorts ...

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NCT01045304 | Study of SAR240550 (BSI-201) in ... Also called a data safety and monitoring board, or DSMB. ... Gemcitabine/Carboplatin, in Patients With Metastatic Triple Negative Breast Cancer (mTNBC).

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Iniparib plus Chemotherapy in Metastatic Triple-Negative ... We conducted an open-label, phase 2 study to compare the efficacy and safety of gemcitabine and carboplatin with or without iniparib, a small ...