Chemotherapy + HER2-Targeted Therapy With or Without Hormone Therapy for Breast Cancer

No longer recruiting at 826 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must be taking: Estrogen deprivation therapy

Must not be taking: Anthracyclines, Taxanes, HER2 therapies, SERMs

Disqualifiers: Metastatic disease, Cardiac disease, 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: 30

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how different drug combinations, with or without hormone therapy, can treat HER2-positive and hormone receptor-positive breast cancer. The trial compares the effectiveness of chemotherapy drugs like docetaxel and carboplatin, combined with targeted therapies trastuzumab and pertuzumab, and possibly hormone therapy, to determine which works best against operable or locally advanced breast cancer. Individuals with HER2-positive breast cancer that is also hormone receptor-positive and operable or locally advanced might be suitable for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I need to stop my current medications to join the trial?

The trial requires that you stop any sex hormonal therapy, such as birth control pills or hormone replacement therapy, before joining. Other medications are not specifically mentioned, so it's best to discuss your current medications with the trial team.

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

Previous studies have found that docetaxel has a manageable safety profile. About 7.7% of patients required hospitalization due to side effects, but these were expected and manageable. Carboplatin, used to treat breast cancer, has proven safe and effective.

Trastuzumab, another drug in this trial, can cause side effects like fever and nausea, but these are common and usually mild. Pertuzumab, often used with trastuzumab and docetaxel, can lead to diarrhea and hair loss, but these side effects are generally not severe.

The hormone therapy, which includes goserelin acetate and aromatase inhibitors, is also generally safe. Goserelin can cause hot flashes, but it is approved for breast cancer treatment. Aromatase inhibitors are well-tolerated even at high doses.

Overall, these treatments have been extensively studied and have a history of being safe for many patients. However, side effects can occur, so monitoring remains important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of chemotherapy, HER2-targeted therapy, and hormone therapy for breast cancer because it offers a multi-faceted approach to treatment. Unlike traditional methods that might focus solely on chemotherapy or hormone therapy, this treatment uses a combination of drugs like docetaxel, carboplatin, trastuzumab, and pertuzumab to target cancer cells from several angles. This approach aims to enhance effectiveness by disrupting cancer cell growth through different pathways, potentially leading to better outcomes. Additionally, the inclusion of hormone therapy for certain patients adds another layer of specificity, targeting hormone-driven cancer growth. This comprehensive strategy could translate into improved survival rates and reduced recurrence for patients with HER2-positive breast cancer.

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

Studies have shown that a combination of four drugs—docetaxel, carboplatin, trastuzumab, and pertuzumab—effectively treats HER2-positive breast cancer. In this trial, participants in Arm I will receive this combination along with surgery and radiation. In some cases, this treatment completely eliminated signs of cancer in about 71.8% of patients. For those with hormone receptor-positive breast cancer, participants in Arm II will receive the same combination therapy with added hormone therapy, which stops estrogen from aiding cancer cell growth, potentially enhancing the treatment's effectiveness. Recent research strongly supports the success of this combination therapy. ^{6 7 8 9 10}

Who Is on the Research Team?

Mothaffar F Rimawi

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

This trial is for patients with hormone receptor-positive, HER2-positive breast cancer that's operable or locally advanced. They should have a life expectancy over 10 years (excluding their diagnosis), normal organ function tests, and no history of certain treatments or conditions like previous malignancies within 5 years. Women must agree to non-hormonal contraception during and post-treatment.

Inclusion Criteria

Your AST blood test results must be within a certain range.

You are expected to live for at least 10 years, not counting your breast cancer diagnosis.

The patient should have good physical ability, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Exclusion Criteria

You have already received radiation, chemotherapy, targeted therapy, or hormone therapy for your current breast cancer before joining the study.

Surgical axillary staging procedure prior to randomization

Excisional biopsy or lumpectomy performed prior to randomization

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Patients receive docetaxel, carboplatin, trastuzumab, and pertuzumab with or without estrogen deprivation every 21 days for up to 6 courses

18 weeks

6 visits (in-person)

Surgery

Patients undergo lumpectomy or mastectomy

1 day

1 visit (in-person)

Radiation

Patients undergo whole breast irradiation within 8 weeks following surgery

8 weeks

Adjuvant Treatment

Patients receive trastuzumab IV every 21 days for up to 1 year

1 year

17 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Every 6, 9, 12, and 18 months

What Are the Treatments Tested in This Trial?

Interventions

• Aromatase Inhibition Therapy
• Carboplatin
• Docetaxel
• Goserelin Acetate
• Pertuzumab
• Therapeutic Conventional Surgery
• Trastuzumab
• Whole Breast Irradiation

Trial Overview The study compares the effectiveness of chemotherapy drugs (docetaxel, carboplatin) combined with targeted therapy (trastuzumab, pertuzumab) with or without estrogen deprivation using goserelin acetate and aromatase inhibitors in treating this type of breast cancer. It also includes radiation therapy and assesses quality-of-life impacts.

How Is the Trial Designed?

Group I: Arm II (chemo, estrogen deprivation, surgery, radiation) Experimental Treatment 11 Interventions

NEOADJUVANT: All patients receive docetaxel, carboplatin, trastuzumab, and pertuzumab as in arm I. Premenopausal patients also receive goserelin acetate SC every 28 days until surgery and aromatase inhibition therapy at the investigator's discretion daily until 1 day before surgery. Postmenopausal patients receive aromatase inhibition therapy at the investigator's discretion daily until 1 day before surgery. Patients enrolled after Amendment #4 undergo 2 core biopsies prior to course 3 of treatment. SURGERY: Patients undergo lumpectomy or mastectomy. RADIATION: Patients undergo whole breast irradiation within 8 weeks following surgery. ADJUVANT: Patients receive trastuzumab IV over 30-60 minutes every 21 days for up to 1 year.

Group II: Arm I (combination chemotherapy, surgery, radiation) Active Control 9 Interventions

NEOADJUVANT: Patients receive docetaxel IV over 60 minutes, carboplatin IV over 30-60 minutes, trastuzumab IV over 30-90 minutes, and pertuzumab IV over 30-60 on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients enrolled after Amendment #4 undergo 2 core biopsies prior to course 3 of treatment. SURGERY: Patients undergo lumpectomy or mastectomy. RADIATION: Patients undergo whole breast irradiation within 8 weeks following surgery. ADJUVANT: Patients receive trastuzumab IV over 30-60 minutes every 21 days for up to 1 year.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

NRG Oncology

Collaborator

Trials

242

Recruited

105,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9582484/

Real World Evidence of Neoadjuvant Docetaxel/ ... Subsequently, many clinical trials have demonstrated successful outcomes with pertuzumab and trastuzumab combination in HER2-positive BCs regardless of ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02003209

Docetaxel, Carboplatin, Trastuzumab, and Pertuzumab ... This randomized phase III trial studies docetaxel, carboplatin, trastuzumab, and pertuzumab with estrogen deprivation to see how they work compared to ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.e12619

Efficacy and safety of neoadjuvant docetaxel, carboplatin ... The TCH-P is an effective, safe, and well-tolerated, protocol with a path CR rate of 55.6% and 26.6% BCS conversion rate from planned MRM.

4. clinicaloncologyonline.net clinicaloncologyonline.net/article/S0936-6555(24)00521-1/fulltext

Efficacy and safety of neoadjuvant Docetaxel, Carboplatin ... Neoadjuvant TCHP was effective and safe in HER2 positive early breast cancer. 71.8% achieved complete pathological response.

5. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(24)00581-3/abstract

a multicentre, randomised, phase 3 trial - The Lancet We aimed to evaluate the efficacy of weekly nab-paclitaxel compared with the standard regimen of docetaxel plus carboplatin, both with ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2503653/

Long-term safety of aromatase inhibitors in the treatment of ... This review will explore the results from the available adjuvant AIs trials with a particular emphasis on safety profiles, quality of life, and therapeutic ...

7. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK557856/

Aromatase Inhibitors - StatPearls - NCBI Bookshelf Clinical trials have shown aromatase inhibitors were well tolerated, even at high doses.[27] There is no established dose of aromatase ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0305737209001923

Adjuvant aromatase inhibitor therapy: Outcomes and safety As with any chronic therapy, the long-term safety profile of endocrine treatments for breast cancer requires careful evaluation. The Anastrozole or Tamoxifen ...

9. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)47560-1/fulltext

Safety profiles of tamoxifen and the aromatase inhibitors in ... Tamoxifen has been used as adjuvant therapy for early breast cancer for many years, and safety data have been well documented, but a poor risk:benefit profile ...

10. nejm.org nejm.org/doi/full/10.1056/NEJMoa2104162

Duration of Adjuvant Aromatase-Inhibitor Therapy in ... Taking these results together, we concluded that there was no firm evidence of a benefit for prolonged aromatase-inhibitor therapy in ...