Pembrolizumab + Chemotherapy for Breast Cancer

Recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Providence Health & Services

Must be taking: Paclitaxel, Capecitabine

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Immunodeficiency, Active TB, Autoimmune, others

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

Compensation: Varies

Number of Visits: 15

Duration: 24 months

29 Participants Needed

Trial Summary

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 be on systemic steroid therapy or any other form of immunosuppressive therapy within 7 days before starting the trial treatment.

What data supports the effectiveness of the drug Pembrolizumab (Keytruda) when used with chemotherapy for breast cancer?

Research shows that Pembrolizumab (Keytruda) has been effective in treating various cancers, including lung and esophageal cancers, by helping the immune system attack cancer cells. Additionally, studies have shown that the combination of capecitabine (Xeloda) and paclitaxel (Taxol) is effective in breast cancer patients who have not responded to other treatments. ^{1 2 3 4 5}

Is the combination of Pembrolizumab and Chemotherapy safe for breast cancer treatment?

Capecitabine (Xeloda), a chemotherapy drug used in combination with others, has been shown to have a favorable safety profile, with common side effects including hand-foot syndrome (redness and swelling of the hands and feet), mouth sores, and diarrhea. It is considered less toxic than some other treatments, making it suitable for outpatient care. ^{3 6 7 8 9}

What makes the drug pembrolizumab unique for breast cancer treatment?

Pembrolizumab is unique because it is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells, and it is being studied in combination with chemotherapy drugs like capecitabine and paclitaxel for breast cancer, which is different from traditional chemotherapy alone. ^{1 2 4 5 10}

What is the purpose of this trial?

The goal of this study is to establish the safety and tolerability of pembrolizumab when administered in combination with either of two chemotherapy regimens (weekly paclitaxel or capecitabine) in unresectable/metastatic triple negative breast cancer (MTNBC) patients.

Research Team

David Page, MD

Principal Investigator

Medical Oncologist

Eligibility Criteria

This trial is for adults with metastatic/unresectable triple negative breast cancer who have not received certain treatments recently. Participants must be in good health, with proper organ function and performance status, and cannot be pregnant or breastfeeding. They should not have active infections or severe psychiatric issues that could affect participation.

Inclusion Criteria

Be willing and able to provide written informed consent/assent for the trial

My breast cancer is HER2-negative.

My breast cancer is not driven by estrogen or progesterone.

Exclusion Criteria

Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment

You are allergic to pembrolizumab or any of its ingredients.

I haven't had cancer treatment with a monoclonal antibody in the last 4 weeks, except for Denosumab.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pilot Phase

Patients are enrolled to one of two experimental arms: pembrolizumab + weekly paclitaxel or pembrolizumab + capecitabine

6 weeks

Weekly visits for paclitaxel or bi-weekly visits for capecitabine

Treatment

Participants receive pembrolizumab every three weeks and continue treatment until disease progression or other discontinuation criteria, up to 24 months

24 months

Every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

CT or MRI scan at 12 weeks

Treatment Details

Interventions

• Capecitabine
• Paclitaxel
• Pembrolizumab

Trial Overview The study tests the safety of pembrolizumab combined with chemotherapy (paclitaxel or capecitabine) for patients with a specific type of advanced breast cancer. The goal is to see how well patients tolerate this combination therapy as their first or second-line treatment.

Participant Groups

Group I: Arm B Experimental Treatment 2 Interventions

pembrolizumab + capecitabine

Group II: Arm A Experimental Treatment 2 Interventions

pembrolizumab + weekly paclitaxel

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

Approved in European Union as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in United States as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in Canada as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in Japan as Xeloda for:

• Colorectal cancer
• Breast cancer

Who Is Running the Clinical Trial?

Providence Health & Services

Lead Sponsor

Trials

131

Recruited

827,000+

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

Findings from Research

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab (Keytruda) is an approved treatment for metastatic or locally advanced esophageal and gastroesophageal junction cancer, indicating its efficacy in targeting these specific cancer types.

It is used in combination with platinum- and fluoropyrimidine-based chemotherapy, suggesting a synergistic approach to enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. Aschenbrenner, DS.[2023]

Pembrolizumab (Keytruda) is approved for treating advanced endometrial carcinoma that is microsatellite instability-high or mismatch repair deficient, specifically for patients whose disease has progressed after previous treatments.

This approval is significant for patients who are not candidates for curative surgery or radiation, providing a new therapeutic option for a challenging stage of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Approved Use for Keytruda. Aschenbrenner, DS.[2022]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Capecitabine (Xeloda) is an oral chemotherapy that delivers 5-FU directly to tumors, offering superior response rates and equivalent survival outcomes compared to intravenous 5-FU in first-line metastatic colorectal cancer (MCRC).

Capecitabine has a favorable safety profile, with manageable side effects like hand-foot syndrome and diarrhea, allowing for prompt dose adjustments without compromising treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of and clinical experience with capecitabine (Xeloda) in the treatment of solid tumours. Sternberg, CN., Reichardt, P., Holland, M.[2015]

A retrospective study of 12 patients with severe renal impairment (GFR <30 mL/min) showed that capecitabine can be safely administered with close monitoring and dose adjustments, despite previous contraindications from the manufacturer based on a small Phase II trial.

Most patients experienced only mild to moderate adverse effects, and some showed a positive response to treatment, indicating that capecitabine may still be effective in this population when managed carefully.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective observational study on the use of capecitabine in patients with severe renal impairment (GFR Jhaveri, KD., Flombaum, C., Shah, M., et al.[2022]

In a study of 42 patients with advanced breast and colorectal cancer, capecitabine showed a partial response rate of 29.16% for breast cancer and 11.76% for colorectal cancer, indicating its potential efficacy in these pretreated patients.

Capecitabine was well tolerated with low toxicity levels, as most adverse reactions were mild, although 7.14% of patients experienced grade 3 hand-foot syndrome, and hypertriglyceridemia was noted in some patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine (Xeloda) as monotherapy in advanced breast and colorectal cancer: effectiveness and side-effects. Stathopoulos, GP., Koutantos, J., Lazaki, H., et al.[2022]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. [2023]

3. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[A comparative randomized phase-II study of Xeloda (capecitabine) and paclitaxel in patients with breast cancer progressing after anthracycline antibiotics]. [2015]

4. United States pubmed.ncbi.nlm.nih.gov

New Approved Use for Keytruda. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

6. Scotland pubmed.ncbi.nlm.nih.gov

Development of and clinical experience with capecitabine (Xeloda) in the treatment of solid tumours. [2015]

7. England pubmed.ncbi.nlm.nih.gov

A retrospective observational study on the use of capecitabine in patients with severe renal impairment (GFR [2022]

8. Greece pubmed.ncbi.nlm.nih.gov

Capecitabine (Xeloda) as monotherapy in advanced breast and colorectal cancer: effectiveness and side-effects. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Capecitabine monotherapy is efficient and safe in all line settings in patients with metastatic and advanced breast cancer. [2015]

10. England pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]