Shorter Chemo-Immunotherapy Without Anthracyclines for Breast Cancer

Recruiting at 996 trial locations

Overseen By Dana Sparks

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: SWOG Cancer Research Network

Must not be taking: Anti-PD-1, Anti-PD-L1

Disqualifiers: Metastatic disease, Uncontrolled diabetes, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 6

Duration: Up to 18 months

2400 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new, shorter chemo-immunotherapy plan for early-stage triple-negative breast cancer. It evaluates whether treatment without anthracyclines (a type of chemotherapy drug) is as effective as the usual treatment that includes them. Participants will receive various combinations of drugs, including paclitaxel, carboplatin, and pembrolizumab (an immunotherapy drug), followed by surgery. This trial may suit those diagnosed with triple-negative breast cancer that has not spread to distant parts of the body and who have not received prior treatment for this cancer. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, you cannot use other investigational agents or have uncontrolled diabetes or hypertension. It's best to discuss your specific medications with the trial team.

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

Research has shown that a combination of the drugs docetaxel, carboplatin, and pembrolizumab has been tested in women with triple-negative breast cancer (TNBC). In one study, this combination was generally well-tolerated, meaning that while patients experienced some side effects, they were mostly manageable.

For another combination of drugs—paclitaxel, carboplatin, pembrolizumab, doxorubicin, and cyclophosphamide—previous trials have demonstrated its safety. Most side effects were not severe and could be managed with care. Pembrolizumab, included in both combinations, is already approved for high-risk early-stage TNBC, indicating its safety in this context.

Overall, both treatment combinations have been studied and are generally considered safe. However, as with any treatment, side effects can occur, and discussing these with the trial team is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they explore a shorter, potentially less toxic, chemo-immunotherapy option for breast cancer. Unlike the usual treatment approach, which includes anthracyclines like doxorubicin, these new treatments aim to avoid such drugs, which are known for their harsh side effects. Additionally, by integrating pembrolizumab, an immunotherapy drug, there's hope to enhance the body's immune response against cancer cells. This could mean not only a gentler treatment experience but also possibly better outcomes for patients.

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

In this trial, participants will receive different treatment combinations for triple-negative breast cancer (TNBC). Research has shown that the combination of docetaxel, carboplatin, and pembrolizumab, which participants in Arm II may receive, is promising. One study found that this combination made tumors completely disappear in 60% of patients, with 88% remaining disease-free for two years. Meanwhile, participants in Arm I will receive a different combination—paclitaxel, carboplatin, and pembrolizumab. Studies indicate that this combination achieved an overall response rate of 48%, with an average survival time of 13.4 months. Both drug combinations show potential in treating early-stage TNBC, offering hope for better outcomes. ^{2 6 7 8 9}

Who Is on the Research Team?

Priyanka Sharma

Principal Investigator

SWOG Cancer Research Network

Are You a Good Fit for This Trial?

This trial is for adults with early-stage triple negative breast cancer who haven't had systemic or radiation therapy, or breast surgery for their current cancer. They must have good heart function and no severe allergies to the study drugs. Participants can't be pregnant/nursing and must agree to use contraception. No live vaccines 30 days before joining, no uncontrolled diseases like diabetes or hypertension, and they shouldn't have a history of certain infections or other cancers that could affect the trial.

Inclusion Criteria

I have never needed steroids for non-infectious lung inflammation.

Participants must not be currently participating in or have participated in a study of an investigational agent or used an investigational device within 28 days prior to randomization

I don't have another cancer that could affect this treatment's safety or results.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive neoadjuvant chemotherapy with pembrolizumab, followed by surgery. Arm I includes paclitaxel, carboplatin, doxorubicin, and cyclophosphamide. Arm II includes docetaxel and carboplatin.

Up to 18 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Every 6 months for the first 2 years, then annually

Optional Pembrolizumab Extension

Participants may receive pembrolizumab after surgery

What Are the Treatments Tested in This Trial?

Interventions

• Biospecimen Collection
• Carboplatin
• Cyclophosphamide
• Docetaxel
• Doxorubicin
• Paclitaxel
• Pembrolizumab
• Surgical Procedure

Trial Overview The trial tests if shorter chemo-immunotherapy without anthracycline drugs (like Doxorubicin) is as effective as usual treatment in early-stage triple negative breast cancer. It involves medications such as Paclitaxel, Carboplatin, Cyclophosphamide, Docetaxel, and Pembrolizumab which target different aspects of cancer cell growth.

How Is the Trial Designed?

Group I: Arm II (shorter chemo-immunotherapy) Experimental Treatment 7 Interventions

Patients receive docetaxel IV, carboplatin IV, and pembrolizumab IV on study. Patients then undergo surgery. Patients may receive pembrolizumab after surgery. Patients may optionally undergo collection of blood samples throughout the trial.

Group II: Arm I (usual chemo-immunotherapy) Active Control 9 Interventions

Patients receive paclitaxel IV, carboplatin IV, and pembrolizumab IV on study. Patients then receive doxorubicin IV, cyclophosphamide IV, and pembrolizumab IV on study. Patients then undergo surgery. Patients may receive pembrolizumab after surgery. Patients may optionally undergo collection of blood samples throughout the trial.

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

Approved in United States as Cytoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in European Union as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Canada as Neosar for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Japan as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma

Who Is Running the Clinical Trial?

SWOG Cancer Research Network

Lead Sponsor

Trials

403

Recruited

267,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Doxorubicin has historically been the most effective treatment for metastatic breast cancer, especially when combined with other agents like 5-fluorouracil and cyclophosphamide, leading to improved patient outcomes.

New agents such as docetaxel have shown significantly higher response rates than doxorubicin in phase III trials, and importantly, docetaxel does not carry the same risk of cardiotoxicity, making it a promising option for combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combining new agents with anthracyclines in metastatic breast cancer: an overview of recent findings. Aapro, MS.[2018]

In a pivotal phase III study involving 429 patients with metastatic breast cancer, the combination of doxorubicin and docetaxel was found to be more effective than doxorubicin plus cyclophosphamide, resulting in higher response rates and longer times to progression and treatment failure.

While febrile neutropenia was more common in patients receiving the doxorubicin/docetaxel combination, there were no septic deaths reported, and the combination did not increase the expected cardiac toxicity associated with anthracyclines, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel (Taxotere) in combination with anthracyclines in the treatment of breast cancer. Nabholtz, JM., North, S., Smylie, M., et al.[2018]

The response to induction chemotherapy is the most important predictor of treatment outcomes in metastatic breast cancer, with anthracyclines and taxanes showing high response rates and long durations of response.

Combination therapies, such as vinorelbine with doxorubicin or epirubicin, have achieved impressive objective response rates, indicating that these combinations can significantly enhance treatment effectiveness for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Chemotherapy of metastatic breast cancer]. Brun, B., Pouillart, P.[2009]

The combination of docetaxel and doxorubicin (TAC) has shown significantly higher response rates in advanced breast cancer treatment compared to traditional regimens, with a response rate of 54% versus 42% for the 5-fluorouracil/doxorubicin/cyclophosphamide regimen, based on a study involving 484 patients.

While TAC treatment was associated with a higher incidence of febrile neutropenia, it did not increase the risk of serious infections or cardiotoxicity, indicating a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel in the treatment of breast cancer: an update on recent studies. Nabholtz, JM., Reese, DM., Lindsay, MA., et al.[2019]

In a pilot phase II study involving 28 patients with metastatic breast cancer, the combination of docetaxel, doxorubicin, and cyclophosphamide showed a high overall response rate of 82%, indicating strong efficacy in treating this condition.

The treatment was associated with significant hematologic toxicity, particularly grade 4 neutropenia in 86% of patients, but there were no severe nonhematologic adverse events or significant cardiotoxicity, suggesting a manageable safety profile when combined with prophylactic antibiotics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel/doxorubicin/cyclophosphamide in the treatment of metastatic breast cancer. Nabholtz, JM., Smylie, M., Mackey, J., et al.[2018]

Docetaxel and doxorubicin combinations (TA or TAC) show high efficacy in treating metastatic breast cancer, with response rates between 70% to 80%, even in patients with visceral metastases.

The main toxicity observed is neutropenia, but significant cardiotoxicity has not been reported, even at high cumulative doses of doxorubicin, indicating a favorable safety profile for these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel and anthracycline polychemotherapy in the treatment of breast cancer. Nabholtz, JM., Smylie, M., Mackey, J., et al.[2018]

Docetaxel has shown a high overall response rate of approximately 60% in phase II studies for metastatic breast cancer and has demonstrated superior efficacy compared to doxorubicin, making it a promising candidate for adjuvant therapy.

The combination of docetaxel with doxorubicin is particularly promising for treating early-stage breast cancer, as it has not been associated with significant heart-related side effects, unlike other combinations, and large phase II trials are currently underway to assess its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of the efficacy and safety of docetaxel as monotherapy in metastatic breast cancer. Crown, J.[2018]

Doxorubicin combined with docetaxel has shown high effectiveness in treating advanced breast cancer without significantly increasing the risk of congestive heart failure, unlike the combination with paclitaxel.

While the combination of doxorubicin and paclitaxel improved response rates, it did not enhance overall survival, highlighting the need for further evaluation of doxorubicin/docetaxel combinations in ongoing clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Compilation of phase I and II trial data of docetaxel and doxorubicin in the treatment of advanced breast cancer and other malignancies. Sparano, JA.[2018]

The combination of pegylated liposomal doxorubicin (Doxil) and docetaxel is safe and effective for treating advanced breast cancer, with a recommended dose of Doxil 30 mg/m² and docetaxel 60 mg/m² every 3 weeks without granulocyte colony-stimulating factor (G-CSF).

The treatment showed promising results, with an objective response rate of 52% in patients with metastatic breast cancer, and infusion reactions were significantly reduced with a modified infusion schedule.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of pegylated liposomal doxorubicin and docetaxel in advanced breast cancer. Sparano, JA., Malik, U., Rajdev, L., et al.[2018]

The combination of doxorubicin and docetaxel has shown high response rates in breast cancer treatment without increasing the risk of cardiomyopathy, making it a safer option compared to the doxorubicin/paclitaxel combination.

Phase III trials confirmed that the doxorubicin/docetaxel regimen improves overall response rates and time to disease progression, suggesting it may be beneficial in both adjuvant and neoadjuvant settings for breast cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Doxorubicin and taxane combination regimens for metastatic breast cancer: focus on cardiac effects. Valero, V., Perez, E., Dieras, V.[2018]

The doxorubicin-docetaxel combination is an effective first-line chemotherapy for metastatic breast cancer, achieving an overall response rate of 67% among 40 assessable patients, with 16% achieving complete remission and 51% partial remission.

The treatment was well-tolerated, with no severe cardiac or neurological toxicity reported, although 58% of patients experienced significant neutropenia, which was managed with G-CSF or GM-CSF support.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-survival in responding patients with metastatic breast cancer treated with doxorubicin-docetaxel combination. A multicentre phase II trial. Mattioli, R., Lippe, P., Massacesi, C., et al.[2018]

The combination of doxorubicin (Dox) and paclitaxel has been established as a superior treatment for metastatic breast cancer, showing better response rates and longer time to disease progression compared to either drug alone, based on a phase III study.

New agents like Herceptin (trastuzumab) and DPPE are being investigated to enhance the efficacy of Dox and paclitaxel, with early results indicating they may improve response rates and prolong disease progression time when used in combination with these chemotherapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New developments in chemotherapy of advanced breast cancer. Lebwohl, DE., Canetta, R.[2016]

Citations

1. 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 ...

2. 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.

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.513

Clinical and biomarker results of neoadjuvant phase II ... Conclusions: Neoadjuvant pembrolizumab plus Cb+D regimen yields pCR of 60% and 2-year EFS of 88% in the absence of adjuvant pembrolizumab. The ...

4. 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) ...

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

Pembrolizumab-Based Regimens Gain Ground in TNBC ... TNBC has the worst prognosis among all breast cancer subtypes. Based on [data from] the SEER database, the 5-year overall survival [OS] rate for ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10666040/

NeoPACT Phase 2 Clinical Trial - PMC - PubMed Central This single-group phase 2 clinical trial including 115 evaluable women with TNBC found that neoadjuvant pembrolizumab plus carboplatin and docetaxel showed an ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.589

Neoadjuvant low-dose carboplatin and docetaxel in ... The NeoTOP trial aimed to assess the efficacy and safety of low-dose carboplatin and docetaxel in combination with toripalimab as neoadjuvant therapy for early ...

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9064451/

Targeted Treatment for High-Risk Early-Stage Triple ... The NeoPACT trial is a phase II neoadjuvant study of pembrolizumab with carboplatin and docetaxel in early-stage TNBC, with pCR as the primary ...