Shorter Chemo-Immunotherapy Without Anthracyclines for Breast Cancer

Recruiting at 432 trial locations

Overseen By Dana Sparks

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: SWOG Cancer Research Network

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

Disqualifiers: Metastatic disease, Uncontrolled diabetes, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This phase III trial compares the effects of shorter chemotherapy (chemo)-immunotherapy without anthracyclines to usual chemo-immunotherapy for the treatment of early-stage triple negative breast cancer. Paclitaxel is in a class of medications called anti-microtubule agents. It stops cancer cells from growing and dividing and may kill them. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of cancer cells. Cyclophosphamide is in a class of medications called alkylating agents. It works by damaging the cell's deoxyribonucleic acid (DNA) and may kill cancer cells. It may also lower the body's immune response. Docetaxel is in a class of medications called taxanes. It stops cancer cells from growing and dividing and may kill them. Doxorubicin is an anthracycline chemotherapy drug that damages DNA and may kill cancer cells. Pembrolizumab may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Shorter treatment without anthracycline chemotherapy may work the same as the usual anthracycline chemotherapy treatment for early-stage triple negative breast cancer.

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.

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

Research shows that docetaxel, one of the drugs in the trial, has a high response rate of about 60% in treating metastatic breast cancer and is superior to doxorubicin in terms of response rate. Additionally, combinations of doxorubicin with taxanes like docetaxel have shown impressive response rates in advanced breast cancer, suggesting potential effectiveness in the trial's drug combination. ^{1 2 3 4 5}

Is the combination of doxorubicin and docetaxel safe for breast cancer treatment?

The combination of doxorubicin and docetaxel has been studied for breast cancer treatment and is generally considered safe, with the main concern being neutropenia (a low level of white blood cells), which can lead to infections. However, significant heart-related side effects (cardiotoxicity) were not observed, making it a viable option for many patients. ^{6 7 8 9 10}

What makes the drug combination of Cyclophosphamide, Docetaxel, Doxorubicin, Paclitaxel, and Pembrolizumab unique for breast cancer treatment?

This treatment is unique because it combines multiple drugs, including docetaxel and pembrolizumab, which have shown high activity in breast cancer, without using anthracyclines, which are known for their heart-related side effects. This approach aims to maintain effectiveness while potentially reducing the risk of heart damage associated with traditional anthracycline-based therapies. ^{1 3 6 11 12}

Research Team

Priyanka Sharma

Principal Investigator

SWOG Cancer Research Network

Eligibility Criteria

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 am 18 years old or older.

Trial Timeline

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

Treatment Details

Interventions

• Biospecimen Collection (Procedure)
• Carboplatin (Platinum-containing compounds)
• Cyclophosphamide (Anti-metabolites)
• Docetaxel (Taxanes)
• Doxorubicin (Anti-tumor antibiotic)
• Paclitaxel (Anti-microtubule agents)
• Pembrolizumab (Monoclonal Antibodies)
• Surgical Procedure (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.

Participant Groups

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 Canada, Japan for the following indications:

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+

Findings from Research

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 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]

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]

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]

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]

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 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]

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]

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]

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]

References

1. United States 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. [2018]

2. France pubmed.ncbi.nlm.nih.gov

[Chemotherapy of metastatic breast cancer]. [2009]

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

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

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

New developments in chemotherapy of advanced breast cancer. [2016]

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

Docetaxel in the treatment of breast cancer: an update on recent studies. [2019]

6. Greece pubmed.ncbi.nlm.nih.gov

Long-survival in responding patients with metastatic breast cancer treated with doxorubicin-docetaxel combination. A multicentre phase II trial. [2018]

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

Docetaxel/doxorubicin/cyclophosphamide in the treatment of metastatic breast cancer. [2018]

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

Phase I trial of pegylated liposomal doxorubicin and docetaxel in advanced breast cancer. [2018]

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

Docetaxel and anthracycline polychemotherapy in the treatment of breast cancer. [2018]

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

Doxorubicin and taxane combination regimens for metastatic breast cancer: focus on cardiac effects. [2018]

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

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

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

Docetaxel (Taxotere) in combination with anthracyclines in the treatment of breast cancer. [2018]