Chemotherapy Reduction After Surgery for Breast Cancer

Recruiting in Palo Alto (17 mi)

+1045 other locations

Overseen by Nadine M Tung

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: ECOG-ACRIN Cancer Research Group

Must be taking: HER2-targeted therapy

Disqualifiers: Stage IV cancer, T4/N3 disease, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial studies how well paclitaxel, trastuzumab, and pertuzumab work in eliminating further chemotherapy after surgery in patients with HER2-positive stage II-IIIa breast cancer who have no cancer remaining at surgery (either in the breast or underarm lymph nodes) after pre-operative chemotherapy and HER2-targeted therapy. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Trastuzumab and pertuzumab are both a form of "targeted therapy" because they work by attaching themselves to specific molecules (receptors) on the surface of tumor cells, known as HER2 receptors. When these drugs attach to HER2 receptors, the signals that tell the cells to grow are blocked and the tumor cell may be marked for destruction by the body's immune system. Giving paclitaxel, trastuzumab, and pertuzumab may enable fewer chemotherapy drugs to be given without compromising patient outcomes compared to the usual treatment.

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, it mentions that patients must be willing to receive standard adjuvant therapy, which may include certain medications. It's best to discuss your current medications with the trial team to get a clear answer.

What data supports the effectiveness of the drug combination of Paclitaxel, Pertuzumab, and Trastuzumab for breast cancer?

Research shows that combining trastuzumab and pertuzumab with taxane-based chemotherapy, like Paclitaxel, is effective for treating HER2-positive breast cancer, improving survival rates and reducing tumor size. ^{1 2 3 4 5}

Is the chemotherapy treatment safe for humans?

The treatment involving trastuzumab and pertuzumab, often used with paclitaxel, has been studied for safety, particularly regarding heart health. Some studies report increased heart-related risks, especially when combined with certain other drugs, and paclitaxel can cause hair loss and nerve issues. However, these treatments are generally considered safe with careful monitoring. ^{1 6 7 8 9}

How does the chemotherapy reduction after surgery for breast cancer differ from other treatments?

This treatment is unique because it focuses on reducing the amount of chemotherapy needed after surgery for breast cancer, potentially minimizing side effects while maintaining effectiveness. It involves a combination of drugs like Doxorubicin, Paclitaxel, Cyclophosphamide, Methotrexate, and 5-Fluorouracil, which are administered in a specific sequence to optimize outcomes. ^{1 5 9 10 11}

Research Team

Nadine M Tung

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

This trial is for HER2-positive stage II-IIIa breast cancer patients who've had pre-surgery chemo and targeted therapy with no remaining cancer. They must have proper organ function, no history of invasive breast cancer except certain conditions, not be pregnant or breastfeeding, willing to use contraception, and free from serious medical conditions that could affect study participation.

Inclusion Criteria

My hepatitis B virus is undetectable with treatment.

My cancer was stage II or IIIa when first diagnosed.

My cancer has not spread to my lymph nodes and the tumor is larger than 2.0 cm.

Exclusion Criteria

I've had the required scans for stage III disease or if I had abnormal liver tests or symptoms.

I do not have severe numbness or pain in my hands or feet.

I am currently on hormone therapy for a previous non-invasive breast cancer.

Trial Timeline

Pre-operative/Neoadjuvant Therapy

Patients receive paclitaxel or nab-paclitaxel, trastuzumab, and pertuzumab intravenously. Treatment repeats every 21 days for up to 4 cycles.

12 weeks

4 cycles (in-person visits every 21 days)

Surgery

Patients undergo standard of care lumpectomy and/or mastectomy within 42 days after last dose of neoadjuvant therapy.

6 weeks

1 visit (in-person)

Post-operative/Adjuvant Therapy

Patients with pCR receive trastuzumab and pertuzumab every 21 days for up to 13 cycles. Patients with residual disease receive trastuzumab emtansine for 14 doses.

9 months

13 cycles (in-person visits every 21 days)

Follow-up

Participants are monitored for safety and effectiveness after treatment. Follow-up occurs every 3 months for 2 years, every 6 months for 2-5 years, then annually for 5-15 years.

Long-term

Regular follow-up visits

Treatment Details

Interventions

• Paclitaxel (Anti-microtubule agent)
• Pertuzumab (Monoclonal Antibodies)
• Trastuzumab (Monoclonal Antibodies)

Trial Overview The trial tests if paclitaxel combined with trastuzumab and pertuzumab can eliminate the need for further chemotherapy after surgery in patients without remaining cancer post-pre-op treatment. These drugs aim to stop tumor growth by killing cells or blocking growth signals.

Participant Groups

Group I: Arm B (residual invasive disease after surgery) Experimental Treatment 8 Interventions

PRE-OPERATIVE/NEOADJUVANT THERAPY: Patients receive either paclitaxel or nab-paclitaxel IV on days 1, 8 and 15, or docetaxel IV on day 1 at the discretion of the treating oncologist. Patients also receive trastuzumab IV on day 1 or days 1, 8, and 15, and pertuzumab IV on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. SURGERY: Within 42 days after last dose of neoadjuvant therapy, patients undergo standard of care lumpectomy and/or mastectomy. POST-OPERATIVE/ADJUVANT THERAPY: Patients with remaining tumor after surgery receive standard of care trastuzumab emtansine for 14 doses in the absence of disease progression or unacceptable toxicity. Patients may also receive additional standard of care chemotherapy, as well as hormone therapy if appropriate.

Group II: Arm A (pCR after surgery) Experimental Treatment 8 Interventions

PRE-OPERATIVE/NEOADJUVANT THERAPY: Patients receive either paclitaxel or nab-paclitaxel IV on days 1, 8 and 15, or docetaxel IV on day 1 at the discretion of the treating oncologist. Patients also receive trastuzumab IV on day 1 or days 1, 8, and 15, and pertuzumab IV on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. SURGERY: Within 42 days after last dose of neoadjuvant therapy, patients undergo standard of care lumpectomy and/or mastectomy. POST-OPERATIVE.ADJUVANT THERAPY: Patients with pCR after surgery receive trastuzumab and pertuzumab IV on day 1. Treatment repeats every 21 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity. Patients may also undergo standard of care radiation therapy and receive hormone therapy if appropriate.

Who Is Running the Clinical Trial?

ECOG-ACRIN Cancer Research Group

Lead Sponsor

Trials

122

Recruited

160,000+

Dr. Peter J. O'Dwyer

ECOG-ACRIN Cancer Research Group

Chief Executive Officer since 2012

MD from University of Pennsylvania

Dr. Mitchell D. Schnall

ECOG-ACRIN Cancer Research Group

Chief Medical Officer since 2012

MD, PhD from University of Pennsylvania

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

In a study of 210 patients with ERBB2-positive metastatic breast cancer, the combination of trastuzumab and pertuzumab without chemotherapy showed a 24-month overall survival rate of 79.0%, which is comparable to 78.1% for those receiving the combination with chemotherapy.

Patients receiving the chemotherapy-free regimen had a median progression-free survival of 8.4 months, significantly shorter than the 23.3 months for those who received chemotherapy, but the absence of chemotherapy resulted in fewer adverse events and slight improvements in quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pertuzumab Plus Trastuzumab With or Without Chemotherapy Followed by Emtansine in ERBB2-Positive Metastatic Breast Cancer: A Secondary Analysis of a Randomized Clinical Trial. Huober, J., Weder, P., Ribi, K., et al.[2023]

In a study of 92 patients with stage II or III HER2+ breast cancer receiving neoadjuvant therapy with paclitaxel, trastuzumab, and pertuzumab, 55.4% were able to undergo breast conservation therapy (BCT), indicating the effectiveness of this treatment approach in increasing BCT eligibility.

Of the patients initially ineligible for BCT, 78.6% became eligible after treatment, and 81.8% of those eligible actually underwent BCT, highlighting the potential of neoadjuvant therapy to significantly improve treatment options for patients with larger tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Neoadjuvant Paclitaxel/Trastuzumab/Pertuzumab on Breast Tumor Downsizing for Patients with HER2+ Breast Cancer: Single-Arm Prospective Clinical Trial. Weiss, A., Li, T., Desai, NV., et al.[2023]

In a study of 55 patients with early-stage, HER2-positive breast cancer, the neoadjuvant chemotherapy regimen combining epirubicin, cyclophosphamide, docetaxel, trastuzumab, and pertuzumab resulted in a high complete pathologic response rate of 64.8%.

The regimen demonstrated good cardiac safety, with only one case of significant left ventricular ejection fraction (LVEF) decline and no instances of symptomatic heart dysfunction, indicating that the treatment can be administered without major cardiac risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac safety of neoadjuvant chemotherapy with epirubicin and cyclophosphamide followed by docetaxel/pertuzumab/trastuzumab for HER2-positive breast cancer patients. Douganiotis, G., Grigoriadis, S., Kontovinis, L., et al.[2021]

In the TRAIN-2 study involving 110 patients with HER2-positive breast cancer, the addition of pertuzumab to chemotherapy regimens resulted in neutropenia as the most common hematologic toxicity, affecting 53% of patients in the FEC-T arm and 51% in the PTC arm.

While both regimens showed manageable toxicity, the FEC-T arm had a higher incidence of asymptomatic ejection fraction decrease (24%) compared to the PTC arm (11%), and diarrhea was more common in the PTC arm (18% vs. 5%), indicating different toxicity profiles depending on the chemotherapy backbone used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity of dual HER2-blockade with pertuzumab added to anthracycline versus non-anthracycline containing chemotherapy as neoadjuvant treatment in HER2-positive breast cancer: The TRAIN-2 study. van Ramshorst, MS., van Werkhoven, E., Honkoop, AH., et al.[2022]

In a study of 30 patients with early-stage HER2+ breast cancer, the combination of trastuzumab and vinorelbine (TV) showed a high 5-year invasive disease-free survival rate of 90.9% and a perfect overall survival rate of 100% after a median follow-up of 68 months.

TV was well tolerated, with no cases of alopecia or long-term neuropathy reported, making it a promising alternative for patients who wish to avoid the side effects associated with traditional taxane-based regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant trastuzumab and vinorelbine for early-stage HER2+ breast cancer. McLaughlin, S., Nakajima, E., Bar, Y., et al.[2023]

The ASTER study demonstrated that a 6-month perioperative chemotherapy regimen combining Doxorubicin and Paclitaxel followed by Cyclophosphamide, Methotrexate, and 5-Fluorouracil is safe and effective for breast cancer treatment, with a low incidence of severe toxicities (8.5% grade III-IV hematologic toxicity).

With a follow-up of 6.7 years, the study reported high disease-free survival rates (99.6% at 1 year, 97.1% at 5 years) and overall survival rates (99.6% at 1 year, 94.9% at 5 years), indicating that this chemotherapy regimen is comparable in efficacy to other standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single Institution trial of anthracycline- and taxane-based chemotherapy for operable breast cancer: The ASTER study. Mariani, G., Galli, G., Cavalieri, S., et al.[2019]

Paclitaxel, when combined with doxorubicin, has shown a remarkable 95% objective response rate in chemotherapy-naive patients with metastatic breast cancer, indicating its high efficacy in treating this condition.

The treatment regimen demonstrated no signs of cardiac toxicity, allowing for further testing in patients with smaller tumors to potentially increase the rate of complete remission before surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Future developments for paclitaxel in the treatment of breast cancer. Bonadonna, G.[2015]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Taxane versus vinorelbine in combination with trastuzumab and pertuzumab for first-line treatment of metastatic HER2-positive breast cancer: a retrospective two-center study. [2021]

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

Pertuzumab. Promising for some women with metastatic breast cancer, but more assessment needed. [2016]

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

Pertuzumab Plus Trastuzumab With or Without Chemotherapy Followed by Emtansine in ERBB2-Positive Metastatic Breast Cancer: A Secondary Analysis of a Randomized Clinical Trial. [2023]

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

Impact of Neoadjuvant Paclitaxel/Trastuzumab/Pertuzumab on Breast Tumor Downsizing for Patients with HER2+ Breast Cancer: Single-Arm Prospective Clinical Trial. [2023]

5. Cyprus pubmed.ncbi.nlm.nih.gov

Cardiac safety of neoadjuvant chemotherapy with epirubicin and cyclophosphamide followed by docetaxel/pertuzumab/trastuzumab for HER2-positive breast cancer patients. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Cardiac Safety of Dual Anti-HER2 Therapy in the Neoadjuvant Setting for Treatment of HER2-Positive Breast Cancer. [2018]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Toxicity of dual HER2-blockade with pertuzumab added to anthracycline versus non-anthracycline containing chemotherapy as neoadjuvant treatment in HER2-positive breast cancer: The TRAIN-2 study. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Pertuzumab, trastuzumab, and standard anthracycline- and taxane-based chemotherapy for the neoadjuvant treatment of patients with HER2-positive localized breast cancer (BERENICE): a phase II, open-label, multicenter, multinational cardiac safety study. [2022]

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

Adjuvant trastuzumab and vinorelbine for early-stage HER2+ breast cancer. [2023]

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

Single Institution trial of anthracycline- and taxane-based chemotherapy for operable breast cancer: The ASTER study. [2019]

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

Future developments for paclitaxel in the treatment of breast cancer. [2015]