AZD9833 vs Fulvestrant for Advanced Breast Cancer

(SERENA-2 Trial)

Recruiting at 78 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: AstraZeneca

Must not be taking: Hormone therapy, CYP inhibitors

Disqualifiers: Cardiovascular issues, CNS 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: 2

Duration: Up to 29 months

240 Participants Needed

Trial Summary

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

The trial requires stopping certain medications, including any recent chemotherapy, investigational drugs, or anti-cancer drugs within 14 days before starting the study treatment. You also need to stop using systemic estrogen-containing hormone replacement therapy 6 months before the trial and avoid certain medications that affect liver enzymes. If you were taking tamoxifen, a 4-month break is needed before a biopsy.

What data supports the effectiveness of the drug AZD9833 vs Fulvestrant for advanced breast cancer?

Research shows that Fulvestrant, a drug used in the study, is effective in treating advanced breast cancer in postmenopausal women, with a clinical benefit rate of 82.8% and an overall survival of 43.1 months in real-world settings. It is at least as effective as other treatments like anastrozole, providing a valuable option for patients who have not responded to previous therapies. ^{1 2 3 4 5}

Is Fulvestrant (Faslodex) safe for humans?

Fulvestrant (Faslodex) has been used in various studies for advanced breast cancer and is generally considered safe, with no known agonist effects (it doesn't activate the estrogen receptor). It has been used in patients who have been heavily pre-treated, indicating a level of safety in humans. ^{2 6 7 8 9}

How is the drug AZD9833 different from other treatments for advanced breast cancer?

AZD9833 is a novel oral selective estrogen receptor degrader (SERD) that offers a more convenient administration route compared to fulvestrant, which requires monthly intramuscular injections. This oral availability could provide more flexibility and potentially better adherence for patients with advanced breast cancer. ^{2 4 10 11 12}

What is the purpose of this trial?

This trial compares a new pill (AZD9833) with an existing injection for treating advanced breast cancer in post-menopausal women. It targets women with a specific type of breast cancer that relies on estrogen to grow. Both treatments work by blocking estrogen receptors to slow down or stop cancer growth.

Eligibility Criteria

This trial is for post-menopausal women aged at least 18 with advanced ER-positive HER2-negative breast cancer. They must have had recurrence or progression after endocrine therapy, possibly including CDK4/6 inhibitors, and no more than one chemotherapy for advanced disease. No prior fulvestrant/SERD treatment, good performance status (ECOG/WHO 0-1), and measurable disease are required.

Inclusion Criteria

My cancer returned or worsened after endocrine therapy.

I have had only one hormone therapy for my advanced disease.

I am fully active or can carry out light work.

Exclusion Criteria

My cancer has spread to vital organs or my brain and is not under control.

I haven't had extensive radiation therapy recently.

My bone marrow or organs are not functioning well.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive one of the four treatments (AZD9833 Dose A, B, C, or Fulvestrant) in 4-week cycles until disease progression

Up to 29 months

Scheduled visits until treatment discontinuation

Follow-up

Participants attend 2 safety follow-up visits and continue to be followed for survival

4 weeks

2 visits (in-person)

Long-term follow-up

Participants are monitored for overall survival and other outcomes

Up to 29 months

Treatment Details

Interventions

• AZD9833
• Fulvestrant

Trial Overview The study compares the effectiveness and safety of a new oral drug called AZD9833 against an existing intramuscular drug named Fulvestrant in treating advanced breast cancer. It's a Phase 2 trial where participants are randomly assigned to either treatment group.

Participant Groups

Group I: AZD9833 Dose C Experimental Treatment 1 Intervention

The patients will receive AZD9833 (Dose C).

Group II: AZD9833 Dose B Experimental Treatment 1 Intervention

The patients will receive AZD9833 (Dose B).

Group III: AZD9833 Dose A Experimental Treatment 1 Intervention

The patients will receive AZD9833 (Dose A).

Group IV: Fulvestrant 500 mg Active Control 1 Intervention

The patients will receive Fulvestrant (500 mg).

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Findings from Research

In a study of 171 postmenopausal women with estrogen receptor-positive advanced breast cancer, fulvestrant as a first-line treatment resulted in a median progression-free survival of 14.6 months, demonstrating its effectiveness in prolonging the time before cancer worsens.

The overall survival rate was 43.1 months, with a high clinical benefit rate of 82.8%, indicating that fulvestrant is not only effective but also well tolerated in real-world settings, aligning with results from randomized clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world data of fulvestrant as first-line treatment of postmenopausal women with estrogen receptor-positive metastatic breast cancer. Blancas, I., Olier, C., Conde, V., et al.[2021]

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 study of 423 postmenopausal women with advanced breast cancer, those who progressed on fulvestrant still showed some sensitivity to subsequent endocrine therapies, with 54 patients experiencing clinical benefit from further treatment.

Fulvestrant can be an effective option in the treatment sequence for advanced breast cancer, potentially allowing patients to avoid cytotoxic chemotherapy longer by extending the use of endocrine therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postmenopausal women who progress on fulvestrant ('Faslodex') remain sensitive to further endocrine therapy. Vergote, I., Robertson, JF., Kleeberg, U., et al.[2019]

Fulvestrant, an estrogen receptor antagonist, was effective in treating advanced breast cancer in postmenopausal women, showing an overall clinical benefit in 39% of the 339 patients studied, with better outcomes when used as a first-line treatment.

The treatment was well tolerated, with only 5% of patients experiencing adverse events, and it was particularly beneficial for patients with tumors expressing both estrogen and progesterone receptors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant ("Faslodex"): clinical experience from the Compassionate Use Programme. Steger, GG., Gips, M., Simon, SD., et al.[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]

In a study of 54 postmenopausal women with metastatic breast cancer, fulvestrant demonstrated clinical benefit in 38.9% of patients, with a median time to progression of 6.4 months, indicating its efficacy even after multiple prior treatments.

Fulvestrant was well tolerated, with no severe toxicities (grade 3/4) reported, suggesting it is a safe option for patients with advanced breast cancer who have limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant ('Faslodex') in heavily pretreated postmenopausal patients with advanced breast cancer: single centre clinical experience from the compassionate use programme. Mlineritsch, B., Psenak, O., Mayer, P., et al.[2018]

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]

Fulvestrant was well tolerated and provided clinical benefit to 21% of heavily pre-treated postmenopausal women with advanced breast cancer, with 42% achieving stable disease for at least 12 weeks.

The efficacy of fulvestrant was similar whether given after disease progression or as maintenance therapy, with a median time to progression of 3 months and no significant toxicities reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant in heavily pre-treated patients with advanced breast cancer: results from a single compassionate use programme centre. Catania, C., Ascione, G., Adamoli, L., et al.[2018]

In a presurgical study involving 46 women with ER+ HER2- breast cancer, AZD9496, an oral selective estrogen receptor degrader (SERD), demonstrated biological activity by reducing estrogen receptor (ER) levels, but was not superior to fulvestrant, the standard injectable SERD, in efficacy.

Both AZD9496 and fulvestrant effectively reduced progesterone receptor (PR) and Ki-67 levels, indicating their impact on tumor biology, but no new safety concerns were identified, suggesting that AZD9496 is safe to use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized, Open-label, Presurgical, Window-of-Opportunity Study Comparing the Pharmacodynamic Effects of the Novel Oral SERD AZD9496 with Fulvestrant in Patients with Newly Diagnosed ER+ HER2- Primary Breast Cancer. Robertson, JFR., Evans, A., Henschen, S., et al.[2021]

References

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

Real-world data of fulvestrant as first-line treatment of postmenopausal women with estrogen receptor-positive metastatic breast cancer. [2021]

2. 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]

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

Postmenopausal women who progress on fulvestrant ('Faslodex') remain sensitive to further endocrine therapy. [2019]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Fulvestrant ('Faslodex'): current and future role in breast cancer management. [2018]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Fulvestrant ("Faslodex"): clinical experience from the Compassionate Use Programme. [2018]

6. 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]

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

Fulvestrant ('Faslodex') in heavily pretreated postmenopausal patients with advanced breast cancer: single centre clinical experience from the compassionate use programme. [2018]

8. Spain pubmed.ncbi.nlm.nih.gov

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

9. Netherlands pubmed.ncbi.nlm.nih.gov

Fulvestrant in heavily pre-treated patients with advanced breast cancer: results from a single compassionate use programme centre. [2018]

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

A Randomized, Open-label, Presurgical, Window-of-Opportunity Study Comparing the Pharmacodynamic Effects of the Novel Oral SERD AZD9496 with Fulvestrant in Patients with Newly Diagnosed ER+ HER2- Primary Breast Cancer. [2021]

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

AZD9496: An Oral Estrogen Receptor Inhibitor That Blocks the Growth of ER-Positive and ESR1-Mutant Breast Tumors in Preclinical Models. [2021]

12. New Zealand pubmed.ncbi.nlm.nih.gov

Fulvestrant: A Review in Advanced Breast Cancer Not Previously Treated with Endocrine Therapy. [2018]