Chemoimmunotherapy for Triple-Negative Breast Cancer

(NeoTRACT Trial)

Recruiting at 6 trial locations

Overseen By KUCC Navigation

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: University of Kansas Medical Center

Must not be taking: Steroids, Immunosuppressants, others

Disqualifiers: Metastatic disease, Autoimmune disease, 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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 32 weeks

139 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether immune cells around a tumor influence how effectively the tumor shrinks when treated with a combination of chemotherapy and immunotherapy. The focus is on women with triple-negative breast cancer, which does not respond to hormonal therapies. Participants will receive a mix of drugs, including pembrolizumab (an immunotherapy drug), carboplatin, and docetaxel, with some receiving additional treatments based on immune cell levels in their tumors. Women with hormone receptor-poor, HER2-negative breast cancer who have not undergone previous treatments for their current cancer might be suitable candidates. As a Phase 2 trial, this research measures how well the treatment works in an initial, smaller group of people.

Do I have to stop taking my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are using other investigational agents, have received a live vaccine within 30 days, or are on certain immunosuppressive therapies.

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

Studies have shown that using carboplatin, docetaxel, and pembrolizumab together is generally safe for patients with triple-negative breast cancer. Research involving similar patients found that this treatment was well-tolerated. While some side effects occurred, they were manageable.

For the combination of carboplatin, docetaxel, doxorubicin, cyclophosphamide, and pembrolizumab, evidence also suggests safety and effectiveness. This combination has been used in patients with similar conditions and generally demonstrated a good safety profile.

Side effects are possible with any treatment, but these combinations have been studied extensively, and research supports their safety. Always consult a healthcare provider about potential side effects to understand what to expect and how to manage them. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine chemoimmunotherapy, which is a promising approach for triple-negative breast cancer. This treatment uses a combination of chemotherapy drugs like Carboplatin, Cyclophosphamide, Docetaxel, and Doxorubicin with Pembrolizumab, an immunotherapy drug. Pembrolizumab helps the immune system recognize and fight cancer cells more effectively. Unlike standard treatments that rely solely on chemotherapy, this combination aims to enhance the body's immune response, potentially leading to better outcomes for patients with varying levels of tumor-infiltrating lymphocytes (sTILs). This approach could mean more personalized treatment strategies and improved survival rates for patients with this aggressive form of breast cancer.

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

Research has shown that a combination of carboplatin, docetaxel, and pembrolizumab holds promise for treating triple-negative breast cancer (TNBC). One study found that this combination made the cancer disappear in 58% of patients, proving very effective for more than half of them. In this trial, participants with low sTILs will receive this combination, followed by doxorubicin and cyclophosphamide with pembrolizumab, which has also proved safe and effective for TNBC. Overall, these treatments, especially with pembrolizumab, have shown encouraging results and could help reduce tumors in TNBC patients. ^{4 6 7 8 9}

Who Is on the Research Team?

Priyanka Sharma, MD

Principal Investigator

University of Kansas Medical Center

Are You a Good Fit for This Trial?

This trial is for women aged 18-70 with triple-negative breast cancer (TNBC) that hasn't spread beyond the breasts and lymph nodes. Participants must have tumors that are hormone receptor poor, HER2-negative, no prior treatments or surgeries for their current breast cancer, and good heart function. They should not be pregnant or breastfeeding and must agree to use contraception.

Inclusion Criteria

Your heart's pumping function is normal, as shown by a heart ultrasound or a MUGA scan.

My invasive tumor is not HER2 positive according to the latest guidelines.

My breast cancer is in stages 1C to 3, has possibly spread to nearby lymph nodes but not to distant parts of the body.

Exclusion Criteria

You have had a very bad allergic reaction to pembrolizumab or any of the substances it contains.

History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of this study, interfere with the subject's participation for the full duration of the study, or it is not in the best interest of the subject to participate, in the opinion of the treating investigator

I haven't had a heart attack, stroke, or severe heart issues in the last year and my blood pressure is controlled.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive neoadjuvant chemoimmunotherapy based on sTIL levels, with cycles every 21 days for up to 32 weeks

Up to 32 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Cyclophosphamide
• Docetaxel
• Doxorubicin
• Pembrolizumab

Trial Overview The study tests if immune cells around TNBC affect how well the tumor responds to a combination of chemotherapy drugs (Doxorubicin, Carboplatin, Docetaxel, Cyclophosphamide) plus an immunotherapy drug called Pembrolizumab given before surgery.

How Is the Trial Designed?

Group I: High sTILs (≥30%) Active Control 3 Interventions

Carboplatin (AUC=6) + Docetaxel (75 mg/m2) + Pembrolizumab (200 mg) every 21 days for four cycles.

Group II: Intermediate sTILs (5-29%) Active Control 3 Interventions

Carboplatin (AUC=6) + Docetaxel (75 mg/m2) + Pembrolizumab (200 mg) every 21 days for six cycles.

Group III: Low sTILs (<5%) Active Control 5 Interventions

Carboplatin (AUC=6) + Docetaxel (75 mg/m2) + Pembrolizumab (200 mg) every 21 days for four cycles followed by Doxorubicin (60 mg/m2) + Cyclophosphamide (600 mg/m2) + Pembrolizumab (200 mg) every 14 or 21 days for four cycles.

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?

University of Kansas Medical Center

Lead Sponsor

Trials

527

Recruited

181,000+

Published Research Related to This Trial

Regimens for triple-negative breast cancer (TNBC) that include platinum salts (Pl), pembrolizumab, or bevacizumab significantly improve the rate of pathologic complete response (pCR), indicating their effectiveness in treatment.

However, regimens containing Pl are associated with a higher risk of severe side effects like febrile neutropenia and thrombocytopenia, highlighting the need to balance efficacy with safety in treatment choices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neo-adjuvant therapy for triple-negative breast cancer: Insights from a network meta-analysis. Miyashita, H., Satoi, S., Cruz, C., et al.[2021]

Capecitabine was found to be an effective chemotherapy option for triple-negative breast cancer (TNBC) patients with residual disease after neoadjuvant chemotherapy, showing high efficacy in 60% of patient-derived xenograft (PDX) models, including complete responses in some cases.

RB1 and TYMP proteins were identified as predictive biomarkers for capecitabine response, suggesting that patients with high expression of these proteins may benefit more from this treatment, while RB1 knockdown decreased sensitivity to 5-FU, indicating its role in treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine Efficacy Is Correlated with TYMP and RB1 Expression in PDX Established from Triple-Negative Breast Cancers. Marangoni, E., Laurent, C., Coussy, F., et al.[2019]

Cytotoxic chemotherapy, particularly a sequential anthracycline-taxane combination, remains the standard treatment for moderate-to-high risk triple-negative breast cancer (TNBC), which is known for its poor prognosis.

While platinums show promise in treating TNBC, especially in neoadjuvant and metastatic settings, more long-term data is needed before they can be routinely used in adjuvant therapy, particularly for specific subgroups like BRCA mutation carriers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tailoring adjuvant chemotherapy regimens for patients with triple negative breast cancer. Stover, DG., Winer, EP.[2015]

The combination of doxorubicin (DOX) with ginsenoside Rg3-loaded nanoparticles significantly enhanced immunogenic cell death (ICD) in triple-negative breast cancer (TNBC), leading to a stronger immune response compared to DOX alone.

Using a thermo-sensitive hydrogel to co-deliver DOX and Rg3-PNPs, along with PD-L1 immunotherapy, effectively transformed nonimmunogenic tumors into immunogenic ones, resulting in substantial antitumor effects and improved recruitment of memory T cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ginsenoside Rg3 nanoparticles with permeation enhancing based chitosan derivatives were encapsulated with doxorubicin by thermosensitive hydrogel and anti-cancer evaluation of peritumoral hydrogel injection combined with PD-L1 antibody. Wu, H., Wei, G., Luo, L., et al.[2022]

In a phase II trial involving 93 patients with untreated stage II-III triple-negative breast cancer, the combination of docetaxel and carboplatin (DCb) resulted in a significantly higher pathologic complete response (pCR) rate of 61.4% compared to 38.6% for the standard epirubicin and cyclophosphamide followed by docetaxel (EC-D) regimen.

Both treatment groups showed equivalent overall survival (OS) and event-free survival (EFS) rates after a median follow-up of 37 months, indicating that while DCb is more effective in achieving pCR, it does not compromise long-term survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant docetaxel plus carboplatin vs epirubicin plus cyclophosphamide followed by docetaxel in triple-negative, early-stage breast cancer (NeoCART): Results from a multicenter, randomized controlled, open-label phase II trial. Zhang, L., Wu, ZY., Li, J., et al.[2022]

DZ-2384, a new microtubule-targeting agent, shows strong effectiveness against triple-negative breast cancer (TNBC) in preclinical models, outperforming traditional taxanes like paclitaxel in terms of reduced toxicity and a wider therapeutic window (14-32 compared to 2.0 for paclitaxel).

DZ-2384 not only effectively reduces brain metastatic lesions but also works synergistically with anti-CTLA-4 immunotherapy, suggesting it could enhance treatment outcomes when combined with immune checkpoint inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DZ-2384 has a superior preclinical profile to taxanes for the treatment of triple-negative breast cancer and is synergistic with anti-CTLA-4 immunotherapy. Bernier, C., Soliman, A., Gravel, M., et al.[2019]

The study developed doxorubicin-loaded platelet decoys (PD@Dox) that not only deliver chemotherapy but also induce immunogenic cell death (ICD) in triple-negative breast cancer (TNBC), enhancing the immune response against tumors.

Combining PD@Dox with PD-1 antibody therapy significantly improved treatment efficacy by blocking tumor immune escape and activating T cells, suggesting a promising new approach for TNBC therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Doxorubicin-Loaded Platelet Decoys for Enhanced Chemoimmunotherapy Against Triple-Negative Breast Cancer in Mice Model. Dong, H., Gao, M., Lu, L., et al.[2023]

In a phase II trial involving 45 women with triple-negative breast cancer, the combination of bevacizumab, docetaxel, and carboplatin achieved a pathological complete response (pCR) rate of 42%, indicating significant effectiveness in shrinking tumors before surgery.

The treatment was well-tolerated, with 98% of patients completing therapy and only minor wound healing issues reported, despite a high incidence of neutropenia (84%) as a side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicentre phase II trial of bevacizumab combined with docetaxel-carboplatin for the neoadjuvant treatment of triple-negative breast cancer (KCSG BR-0905). Kim, HR., Jung, KH., Im, SA., et al.[2020]

In a study using patient-derived xenografts from nine chemotherapy-naïve triple-negative breast cancer (TNBC) samples, docetaxel and carboplatin were found to be effective as single agents, while doxorubicin showed low activity.

The combination of docetaxel and carboplatin was more effective than either drug alone, particularly in models without hereditary mutations, highlighting the potential for optimized treatment strategies in TNBC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity of docetaxel, carboplatin, and doxorubicin in patient-derived triple-negative breast cancer xenografts. Martin, M., Ramos-Medina, R., Bernat, R., et al.[2021]

In a study of 190 patients with stage I-III triple-negative breast cancer (TNBC), the neoadjuvant regimen of carboplatin and docetaxel (CbD) achieved a high pathologic complete response (pCR) rate of 55%, indicating effective tumor reduction before surgery.

The CbD regimen was well tolerated, with only 21% of patients experiencing grade 3 or 4 adverse events, suggesting it is a safe treatment option comparable to traditional chemotherapy combinations that include anthracyclines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Neoadjuvant Carboplatin plus Docetaxel in Triple-Negative Breast Cancer: Combined Analysis of Two Cohorts. Sharma, P., López-Tarruella, S., García-Saenz, JA., et al.[2022]

In a clinical trial involving 90 patients with triple negative breast cancer (TNBC), the optimal chemotherapy regimen combined carboplatin with standard dose-dense ACT, resulting in the lowest grade 3 or 4 toxicities and no delays or dose reductions for carboplatin.

The study identified reduced protein levels of androgen receptor and PD-L1 as potential indicators of treatment response, with Stage I patients showing a zero relapse rate, suggesting the effectiveness of the carboplatin-based regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective phase II clinical trial identifying the optimal regimen for carboplatin plus standard backbone of anthracycline and taxane-based chemotherapy in triple negative breast cancer. Hamm, C., Fifield, BA., Kay, A., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37991778/

NeoPACT Phase 2 Clinical Trial - PubMed - NIH The findings of the phase 2 clinical trial indicate that neoadjuvant carboplatin and docetaxel plus pembrolizumab shows encouraging pCR and 3-year EFS.

2. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2812294

Clinical and Biomarker Findings of Neoadjuvant ... This single-group phase 2 clinical trial including 115 evaluable women with TNBC found that neoadjuvant pembrolizumab plus carboplatin and docetaxel showed an ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03639948

NCT03639948 | Neoadjuvant Phase II Study of ... However, because TNBC is usually more aggressive, harder to treat, and more likely to come back, it is associated with poor long-term outcomes (survival rates) ...

4. onclive.com onclive.com/view/pembrolizumab-based-regimens-gain-ground-in-tnbc-management

Pembrolizumab-Based Regimens Gain Ground in TNBC ... It was a single-arm, phase 2 trial using docetaxel plus carboplatin and pembrolizumab given every 3 weeks for 6 cycles. ... triple-negative breast ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11092992/

Updates on the preoperative immunotherapy for triple ... The phase II NeoPACT trial evaluated 109 TNBC patients receiving six cycles of neoadjuvant carboplatin and docetaxel with pembrolizumab and produced a 58% pCR ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10463750/

Neoadjuvant immunotherapy and chemotherapy regimens for ... Clinical trial evidence suggests that neoadjuvant pembrolizumab + chemotherapy followed by adjuvant pembrolizumab is an effective and safe ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11324725/

Dose dense versus 3 weekly AC during neoadjuvant ... Neoadjuvant pembrolizumab plus chemotherapy (P + CT) has emerged as a standard of care for stage II-III triple-negative breast cancer (TNBC).

8. hemonc.org hemonc.org/wiki/Early_breast_cancer,_triple_negative

Early breast cancer, triple negative This page has regimens which are specific to early breast cancer that is estrogen receptor-negative, progesterone receptor-negative, and HER2-negative (triple ...

9. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.17_suppl.LBA509

NRG-BR003: A randomized phase III trial comparing ... A randomized phase III trial comparing doxorubicin plus cyclophosphamide followed by weekly paclitaxel with or without carboplatin for node-positive or high- ...