Chemoimmunotherapy for Triple-Negative Breast Cancer

(NeoTRACT Trial)

Recruiting at 6 trial locations

Overseen By KUCC Navigation

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: University of Kansas Medical Center

Must not be taking: Steroids, Immunosuppressants, others

Disqualifiers: Metastatic disease, Autoimmune disease, others

Stay on Your Current Meds

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial will study if having certain cells around the tumor helps shrink it in patients with a specific type of breast cancer who are receiving a combination of treatments before surgery. The goal is to see if these cells and imaging tests can help customize treatment for better results. Recent developments have shown that some aggressive types of this breast cancer are resistant to treatment and have a poor prognosis.

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.

What data supports the effectiveness of the drug combination used in the clinical trial for triple-negative breast cancer?

Research shows that the combination of docetaxel and carboplatin is effective against triple-negative breast cancer, with most patient-derived models responding well to these drugs. Additionally, adding carboplatin to standard chemotherapy has improved response rates in patients, and early data suggests that this combination can be optimized for better outcomes. ^{1 2 3 4 5}

Is chemoimmunotherapy for triple-negative breast cancer safe for humans?

The combination of docetaxel and carboplatin has been studied in triple-negative breast cancer and is associated with relevant toxicity, meaning it can cause significant side effects. However, it is generally considered active against this type of cancer, especially in certain genetic backgrounds. ^{4 5 6 7 8}

What makes the chemoimmunotherapy drug for triple-negative breast cancer unique?

This treatment combines chemotherapy drugs with an immune checkpoint inhibitor, pembrolizumab, which may enhance the immune system's ability to fight cancer. The inclusion of carboplatin, a platinum-based drug, is promising for improving outcomes in triple-negative breast cancer, especially when combined with other chemotherapy agents like docetaxel and doxorubicin. ^{1 5 9 10 11}

Research Team

Shane Stecklein, MD, PhD

Principal Investigator

University of Kansas Medical Center

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Carboplatin (Chemotherapy)
• Cyclophosphamide (Chemotherapy)
• Docetaxel (Chemotherapy)
• Doxorubicin (Chemotherapy)
• Pembrolizumab (Monoclonal Antibodies)

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.

Participant Groups

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 Canada for the following indications:

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

1. United States 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. [2022]

2. England 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). [2020]

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

Neo-adjuvant therapy for triple-negative breast cancer: Insights from a network meta-analysis. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Activity of docetaxel, carboplatin, and doxorubicin in patient-derived triple-negative breast cancer xenografts. [2021]

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

Efficacy of Neoadjuvant Carboplatin plus Docetaxel in Triple-Negative Breast Cancer: Combined Analysis of Two Cohorts. [2022]

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

Capecitabine Efficacy Is Correlated with TYMP and RB1 Expression in PDX Established from Triple-Negative Breast Cancers. [2019]

7. United States 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. [2022]

8. England 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. [2019]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Tailoring adjuvant chemotherapy regimens for patients with triple negative breast cancer. [2015]

10. England 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. [2022]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Doxorubicin-Loaded Platelet Decoys for Enhanced Chemoimmunotherapy Against Triple-Negative Breast Cancer in Mice Model. [2023]