Giredestrant + Hormone Therapy for Early-Stage Breast Cancer

Recruiting at 871 trial locations

Overseen By Reference Study ID Number: GO42784 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

Must not be taking: CDK4/6 inhibitors, CYP3A4 inhibitors

Disqualifiers: Stage IV breast cancer, Cardiac disease, Liver disease, others

Stay on Your Current Meds You can continue your current medications while participating

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: Unknown

Duration: 5 years

4200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing giredestrant, a medication given after initial treatment to prevent breast cancer from returning. It focuses on patients with a specific type of early-stage breast cancer that is hormone-driven and at higher risk of recurrence. Giredestrant works by blocking the hormone estrogen from helping cancer cells grow. Giredestrant has shown promise in previous studies.

Will I have to stop taking my current medications?

The trial requires a washout period (time without taking certain medications) of at least 21 days after the last dose of adjuvant chemotherapy before starting the study. Additionally, you cannot take strong CYP3A4 inhibitors or inducers within 14 days before starting the study treatment. If you are on these medications, you may need to stop them before participating.

Is Giredestrant + Hormone Therapy safe for humans?

Endocrine therapies, including tamoxifen and aromatase inhibitors, are generally considered safe for treating breast cancer, but they can have side effects that affect quality of life, such as cognitive issues and other adverse effects. It's important to discuss these potential side effects with your healthcare provider to ensure they are managed effectively. ^{1 2 3 4 5}

What makes the drug Giredestrant unique for early-stage breast cancer?

Giredestrant is unique because it is a selective estrogen receptor degrader (SERD), which means it works by breaking down estrogen receptors in cancer cells, potentially offering a different mechanism compared to traditional hormone therapies that only block estrogen production or action. ^{6 7 8 9 10}

What data supports the effectiveness of the drug Giredestrant combined with hormone therapy for early-stage breast cancer?

Endocrine therapy, which includes hormone treatments like tamoxifen and aromatase inhibitors, has been shown to reduce the risk of recurrence and death in women with hormone receptor-positive breast cancer. These therapies are well-established in both early-stage and advanced breast cancer, suggesting potential benefits when combined with new agents like Giredestrant. ^{2 7 11 12 13}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

This trial is for adults with early-stage, estrogen receptor-positive, HER2-negative breast cancer who've had surgery and possibly chemotherapy (with a 21-day gap before joining the study). They should be within 12 months post-surgery, have no prior endocrine therapy or other cancers in the last 3 years, and must not be pregnant. Good organ function and performance status are required.

Inclusion Criteria

My breast cancer is estrogen receptor positive and HER2 negative.

I finished my additional chemotherapy at least 3 weeks ago.

All my breast cancer tumors are ER positive and HER2 negative.

Exclusion Criteria

Received treatment with investigational therapy within 28 days prior to initiation of study treatment or is currently enrolled in any other type of medical research judged by the sponsor not to be scientifically or medically compatible with this study

I am taking or will take a CDK4/6 inhibitor for early-stage cancer treatment.

I have severe liver disease, such as hepatitis or cirrhosis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive adjuvant giredestrant or endocrine therapy of physician's choice

5 years

Substudy Treatment

Participants in the substudy receive giredestrant in combination with abemaciclib for up to 2 years, followed by giredestrant monotherapy for an additional 3 years

5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Endocrine Therapy of Physician's Choice
• Giredestrant
• LHRH Agonist

Trial Overview The study compares Giredestrant, a new drug for breast cancer treatment after surgery (adjuvant), to standard endocrine therapies chosen by physicians. It's an open-label Phase III trial where participants are randomly assigned to either treatment group.

How Is the Trial Designed?

Group I: Substudy: Giredestrant + Abemaciclib, Then Giredestrant Experimental Treatment 2 Interventions

In this substudy, participants will receive giredestrant in combination with abemaciclib for up to 2 years. Participants will continue with giredestrant monotherapy for an additional 3 years in order to complete a total of 5 years on study treatment.

Group II: Arm A: Giredestrant Experimental Treatment 2 Interventions

Group III: Arm B: Endocrine Therapy of Physician's Choice Active Control 2 Interventions

Endocrine Therapy of Physician's Choice is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Endocrine Therapy for:

• Breast cancer
• Prostate cancer
• Endometrial cancer
• Ovarian cancer

Approved in United States as Hormone Therapy for:

• Breast cancer
• Prostate cancer
• Endometrial cancer
• Ovarian cancer

Approved in Canada as Endocrine Therapy for:

• Breast cancer
• Prostate cancer
• Endometrial cancer
• Ovarian cancer

Approved in Japan as Hormone Therapy for:

• Breast cancer
• Prostate cancer
• Endometrial cancer
• Ovarian cancer

Approved in China as Endocrine Therapy for:

• Breast cancer
• Prostate cancer
• Endometrial cancer
• Ovarian cancer

Approved in Switzerland as Hormone Therapy for:

• Breast cancer
• Prostate cancer
• Endometrial cancer
• Ovarian cancer

Who Is Running the Clinical Trial?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Published Research Related to This Trial

Endocrine therapy is essential for treating premenopausal women with early-stage hormone receptor-positive breast cancer, but there is still uncertainty about the best strategies for using tamoxifen and estrogen deprivation alongside chemotherapy.

Research is ongoing to find better markers for predicting how well patients will respond to endocrine therapy and to understand the unique side effects that young women may experience from this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant hormonal therapy for premenopausal women with breast cancer. Brown, RJ., Davidson, NE.[2015]

Endocrine therapy, particularly targeting estrogen receptors (ER), is crucial for treating both primary and advanced breast cancer, with ER status being the best predictor of treatment response.

New agents, such as pure anti-estrogens and third-generation selective aromatase inhibitors, are emerging as effective alternatives to traditional treatments like Tamoxifen, and ongoing research aims to enhance their use in preoperative settings and for chemoprevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endocrine therapy for breast cancer: an overview. Cheung, KL.[2022]

The combination of S-1 and fulvestrant showed significantly enhanced antitumor activity in estrogen-responsive breast cancer (MCF-7) compared to either treatment alone, indicating a potential new effective therapy.

Fulvestrant not only inhibited tumor growth but also significantly down-regulated estrogen and progesterone receptor levels when combined with S-1, suggesting a mechanism that may improve treatment outcomes in hormone-responsive breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Estrogen Down-regulator Fulvestrant Potentiates Antitumor Activity of Fluoropyrimidine in Estrogen-responsive MCF-7 Human Breast Cancer Cells. Nukatsuka, M., Saito, H., Noguchi, S., et al.[2020]

Endocrine therapy, particularly with tamoxifen, has improved safety and rationale in treating breast cancer, but uncertainties remain regarding its effectiveness compared to chemotherapy, especially in adjuvant settings.

In advanced breast cancer, a sequential approach using either endocrine therapy or chemotherapy is preferred over concurrent treatment, although specific clinical situations may warrant the latter approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Results and limits of endocrine therapy of carcinoma of the breast]. Cocconi, G.[2006]

Endocrine therapy, particularly with tamoxifen, is a key treatment for women with steroid receptor-positive breast cancers, significantly lowering the risk of recurrence and death.

For premenopausal women, ovarian suppression is a crucial option, while postmenopausal women may benefit from aromatase inhibitors, highlighting the need for ongoing research into the best treatment sequences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Adjuvant treatment of breast cancer. Endocrine therapy]. Mouridsen, HT., Andersen, J.[2013]

Adjuvant endocrine treatment is crucial for postmenopausal women with hormone receptor-positive breast cancer, with options including tamoxifen and aromatase inhibitors, each having unique side effects.

For premenopausal women, tamoxifen is the standard treatment, and ongoing research is exploring the potential benefits of adding ovarian suppression to enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant hormonal therapy for early-stage breast cancer. Burstein, HJ., Griggs, JJ.[2010]

Tamoxifen has been the standard treatment for premenopausal women with breast cancer for over 30 years, but adding ovarian function suppression to endocrine therapy can lead to better outcomes for selected patients.

Extended therapy duration is becoming a new standard of care for high-risk patients, and ongoing research is focused on developing new drugs to overcome endocrine resistance, highlighting the importance of personalized treatment plans that consider side effects and quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Modern Landscape of Endocrine Therapy for Premenopausal Women with Breast Cancer. Rossi, L., Pagani, O.[2020]

Endocrine therapy is crucial for treating breast cancer but can lead to cognitive dysfunction, which is common and often underreported, affecting patients' quality of life and treatment adherence.

A comprehensive literature review highlights the need for proactive management of cognitive side effects associated with endocrine therapies, emphasizing the importance of a multi-disciplinary approach to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Endocrine Therapy on Cognitive Function in Patients with Breast Cancer: A Comprehensive Review. Haggstrom, LR., Vardy, JL., Carson, EK., et al.[2022]

Endocrine therapy is crucial for treating endocrine-sensitive breast cancer, significantly lowering recurrence rates and mortality when administered for 5 years in the adjuvant setting.

Tamoxifen is preferred for premenopausal women, while aromatase inhibitors are standard for postmenopausal women; however, managing side effects is essential to ensure patient compliance and improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Endocrine therapy in breast cancer: efficacy and adverse events]. Odermatt, R., Wolfer, A., Zaman, K.[2013]

In a study of 81 patients with metastatic breast cancer, Exemestane (EXE) demonstrated moderate efficacy as a second-line treatment, achieving a clinical benefit rate (CBR) of 39% after Anastrozole (ANA) failed.

Patients with only bone and soft tissue metastases had better outcomes with EXE compared to those with visceral metastases, suggesting that EXE may be particularly effective in certain metastatic profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Examination of the use of Exemestane in patients with metastatic breast cancer. Takashima, S., Kiyoto, S., Takahashi, M., et al.[2016]

Aromatase inhibitors (AIs) provide a significant survival benefit for postmenopausal women with advanced breast cancer compared to other endocrine therapies, with a pooled hazard ratio of 0.90 based on 31 trials involving 11,403 women.

AIs have a different toxicity profile than other endocrine treatments, showing similar rates of hot flushes and arthralgia, but significantly lower risks of vaginal bleeding (71% decrease) and thromboembolic events (47% decrease).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aromatase inhibitors for treatment of advanced breast cancer in postmenopausal women. Gibson, L., Lawrence, D., Dawson, C., et al.[2022]

Fulvestrant is a selective estrogen receptor down-regulator (SERD) that has shown significant efficacy and a strong safety profile in treating postmenopausal women with hormone-receptor positive metastatic breast cancer.

Combining fulvestrant with targeted therapies has demonstrated increased effectiveness, suggesting it may become a new standard treatment, with ongoing clinical trials (FALCON and FEVEX) expected to provide further insights into its optimal use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of fulvestrant in the treatment of postmenopausal metastatic breast cancer patients. Poggio, F., Lambertini, M., Blondeaux, E., et al.[2018]

Anti-aromatase agents, such as exemestane and anastrozole, have shown better tolerability and improved efficacy compared to megestrol acetate for postmenopausal women with advanced breast cancer who have progressed after tamoxifen therapy.

These agents are now considered the preferred endocrine treatment option due to their demonstrated survival benefits and effectiveness in patients who have failed multiple hormonal therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of anti-aromatase agents in postmenopausal advanced breast cancer. Murray, R.[2019]

Citations

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

Adjuvant hormonal therapy for premenopausal women with breast cancer. [2015]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Endocrine therapy for breast cancer: an overview. [2022]

3. Greece pubmed.ncbi.nlm.nih.gov

Estrogen Down-regulator Fulvestrant Potentiates Antitumor Activity of Fluoropyrimidine in Estrogen-responsive MCF-7 Human Breast Cancer Cells. [2020]

4. Italy pubmed.ncbi.nlm.nih.gov

[Results and limits of endocrine therapy of carcinoma of the breast]. [2006]

5. Denmark pubmed.ncbi.nlm.nih.gov

[Adjuvant treatment of breast cancer. Endocrine therapy]. [2013]

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

Adjuvant hormonal therapy for early-stage breast cancer. [2010]

7. Switzerland pubmed.ncbi.nlm.nih.gov

The Modern Landscape of Endocrine Therapy for Premenopausal Women with Breast Cancer. [2020]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Effects of Endocrine Therapy on Cognitive Function in Patients with Breast Cancer: A Comprehensive Review. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

[Endocrine therapy in breast cancer: efficacy and adverse events]. [2013]

10. Japan pubmed.ncbi.nlm.nih.gov

Examination of the use of Exemestane in patients with metastatic breast cancer. [2016]

11. England pubmed.ncbi.nlm.nih.gov

Aromatase inhibitors for treatment of advanced breast cancer in postmenopausal women. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Role of fulvestrant in the treatment of postmenopausal metastatic breast cancer patients. [2018]

13. Germany pubmed.ncbi.nlm.nih.gov

Role of anti-aromatase agents in postmenopausal advanced breast cancer. [2019]