Giredestrant for Advanced Breast Cancer

Recruiting at 112 trial locations

Overseen By Reference Study ID Number: WO42312 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Hoffmann-La Roche

Must be taking: LHRH agonists

Must not be taking: Investigational therapies

Disqualifiers: CNS metastases, Cardiac disease, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to approximately 36 months

303 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing giredestrant, a new drug, to see if it works better than usual hormone treatments for certain breast cancer patients. It targets patients whose cancer grows with the help of estrogen and who have already tried other treatments. The drug aims to block a protein that helps the cancer grow.

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

The trial protocol does not specify if you need to stop taking your current medications. However, if you are taking a selective estrogen receptor degrader (SERD) other than fulvestrant, you may need to stop, as prior treatment with SERDs is an exclusion criterion.

What data supports the effectiveness of the drug Giredestrant for advanced breast cancer?

Research shows that Fulvestrant, a component of the treatment, is effective for advanced breast cancer, providing similar benefits to other drugs like anastrozole and exemestane. This suggests that the combination of treatments, including Giredestrant, may offer effective options for patients. ^{1 2 3 4 5}

Is Giredestrant safe for humans?

Fulvestrant, a similar treatment to Giredestrant, has been studied for safety in treating advanced breast cancer. It has shown a tolerable safety profile with no significant differences in adverse events compared to other treatments like exemestane. ^{3 4 6 7 8}

What makes the drug Giredestrant unique for advanced breast cancer?

Giredestrant is unique because it is a selective estrogen receptor down-regulator (SERD) that targets and degrades the estrogen receptor without any agonist effects, unlike tamoxifen, which has both agonist and antagonist effects. This makes it a promising option for patients whose cancer has become resistant to other treatments like tamoxifen. ^{4 6 9 10 11}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for postmenopausal or premenopausal women with ER-positive, HER2-negative advanced breast cancer who've had 1-2 systemic therapies but not more than one targeted therapy. They must have good organ function and agree to LHRH agonist therapy if premenopausal. Exclusions include active heart disease, uncontrolled brain metastases, life-threatening visceral spread, prior SERD treatment (except fulvestrant), investigational drug use within 28 days, or being pregnant/breastfeeding.

Inclusion Criteria

My breast cancer cannot be cured with surgery or radiation.

I am willing to undergo hormone therapy if I am a premenopausal or perimenopausal woman, or a man.

My tumor is ER-positive and HER2-negative.

Exclusion Criteria

I have not been treated with SERDs, except for fulvestrant which I stopped at least 28 days ago.

Treatment with any investigational therapy within 28 days prior to randomization

My cancer has spread to vital organs and could cause serious health issues.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive giredestrant or physician's choice of endocrine monotherapy

Up to approximately 36 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Aromatase Inhibitor (Physician's Choice)
• Fulvestrant
• Giredestrant

Trial Overview The study compares the effectiveness of Giredestrant against a physician's choice of endocrine monotherapy in patients with certain types of advanced breast cancer. It's an open-label Phase II trial where participants are randomly assigned to receive either Giredestrant or another hormone therapy chosen by their doctor.

Participant Groups

Group I: Giredestrant Experimental Treatment 2 Interventions

Group II: Physician Choice of Endocrine Monotherapy Active Control 2 Interventions

The physician choice of endocrine monotherapy will be limited to fulvestrant or an aromatase inhibitor.

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

Findings from Research

Fulvestrant (Faslodex) is as effective as anastrozole (Arimidex) for treating advanced breast cancer in postmenopausal women, with similar objective response rates across different patient subgroups.

Both treatments provided comparable clinical benefits, making fulvestrant a valuable option for patients with visceral metastases who have not responded to previous endocrine therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant (Faslodex) versus anastrozole for the second-line treatment of advanced breast cancer in subgroups of postmenopausal women with visceral and non-visceral metastases: combined results from two multicentre trials. Mauriac, L., Pippen, JE., Quaresma Albano, J., et al.[2019]

In a phase II study involving 205 postmenopausal women with advanced hormone receptor-positive breast cancer, high-dose fulvestrant (500 mg/month) showed a clinical benefit rate (CBR) similar to anastrozole (72.5% vs. 67.0%), indicating comparable effectiveness as first-line therapy.

Fulvestrant high-dose was associated with a significantly longer time to progression (TTP) compared to anastrozole, suggesting it may provide a more durable response in treatment, while both therapies had similar safety profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity of fulvestrant 500 mg versus anastrozole 1 mg as first-line treatment for advanced breast cancer: results from the FIRST study. Robertson, JF., Llombart-Cussac, A., Rolski, J., et al.[2022]

The EFECT trial is the first Phase III study showing that fulvestrant is an effective treatment option for postmenopausal women with advanced breast cancer who have progressed on aromatase inhibitors, demonstrating similar efficacy to exemestane.

Both fulvestrant and exemestane had comparable safety profiles, with no significant differences in adverse events reported, indicating that fulvestrant can be a viable alternative after AI failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant: expanding the endocrine treatment options for patients with hormone receptor-positive advanced breast cancer. Chia, S., Gradishar, W.[2018]

In a study involving 587 postmenopausal women with advanced breast cancer, fulvestrant showed similar efficacy to tamoxifen in patients with hormone receptor-positive tumors, with no significant differences in time to progression (TTP) or objective response rates.

While tamoxifen had a slightly better overall efficacy in the general population, both treatments were well tolerated, indicating that fulvestrant can be a viable option for patients with ER+ and/or PgR+ tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of fulvestrant versus tamoxifen for the treatment of advanced breast cancer in postmenopausal women previously untreated with endocrine therapy: a multinational, double-blind, randomized trial. Howell, A., Robertson, JF., Abram, P., et al.[2022]

Aromatase inhibitors (AIs) like letrozole and anastrozole are effective first-line treatments for postmenopausal women with metastatic breast cancer, showing better efficacy and fewer side effects compared to the traditional antiestrogen tamoxifen.

Clinical studies and preclinical models indicate that AIs significantly suppress estrogen synthesis, leading to improved patient outcomes and suggesting potential benefits when combined with other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Applicability of the intratumor aromatase preclinical model to predict clinical trial results with endocrine therapy. Brodie, AH., Mouridsen, HT.[2019]

Faslodex (fulvestrant) is a novel selective estrogen receptor down-regulator (SERD) that effectively targets and degrades the estrogen receptor, offering a new treatment option for advanced breast cancer, especially in cases where tumors have become resistant to tamoxifen.

Unlike tamoxifen, which can lead to resistance and has risks such as endometrial carcinoma, Faslodex provides a 'pure' antiestrogen effect without agonistic activity, making it a promising alternative for both advanced and early breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Faslodex(TM) for the treatment of breast cancer. Smolnikar, K.[2019]

Third-generation aromatase inhibitors (AIs) like anastrozole, letrozole, and exemestane have emerged as effective alternatives to tamoxifen for treating postmenopausal breast cancer, particularly in hormone receptor-positive cases, as shown in the ATAC trial with over five years of follow-up.

Fulvestrant, a new type of estrogen receptor antagonist with no partial agonist activity, represents a promising option in breast cancer treatment, and the review discusses future sequencing strategies for using AIs earlier in treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New developments in the treatment of postmenopausal breast cancer. Howell, A.[2018]

References

1. England pubmed.ncbi.nlm.nih.gov

Fulvestrant (Faslodex) versus anastrozole for the second-line treatment of advanced breast cancer in subgroups of postmenopausal women with visceral and non-visceral metastases: combined results from two multicentre trials. [2019]

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

Activity of fulvestrant 500 mg versus anastrozole 1 mg as first-line treatment for advanced breast cancer: results from the FIRST study. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Fulvestrant: expanding the endocrine treatment options for patients with hormone receptor-positive advanced breast cancer. [2018]

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

Comparison of fulvestrant versus tamoxifen for the treatment of advanced breast cancer in postmenopausal women previously untreated with endocrine therapy: a multinational, double-blind, randomized trial. [2022]

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

Applicability of the intratumor aromatase preclinical model to predict clinical trial results with endocrine therapy. [2019]

6. Spain pubmed.ncbi.nlm.nih.gov

Faslodex(TM) for the treatment of breast cancer. [2019]

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

New developments in the treatment of postmenopausal breast cancer. [2018]

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

Aromatase inhibitors: a safety comparison. [2019]

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

An overview of the use of non-steroidal aromatase inhibitors in the treatment of breast cancer. [2019]

10. Greece pubmed.ncbi.nlm.nih.gov

New aromatase inhibitors in the treatment of advanced breast cancer. [2019]

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

Anastrozole. An effective, second-line hormonal treatment for advanced breast cancer. [2018]