AZD9833 vs Fulvestrant for Advanced Breast Cancer

(SERENA-2 Trial)

Not currently recruiting at 95 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness and safety of the new oral medication AZD9833 compared to the standard treatment, fulvestrant (an estrogen receptor antagonist), for women with advanced breast cancer. The aim is to determine which treatment better slows or stops the cancer. Participants will receive either AZD9833 in varying doses or fulvestrant. Women who have experienced progression in their breast cancer after previous treatments and have not been treated with fulvestrant may be suitable for this study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research has shown that AZD9833, a new treatment for advanced breast cancer, is generally safe. Testing on patients with similar conditions indicates it is usually well-tolerated. Some mild side effects have been reported, but they are manageable.

Fulvestrant, an approved and commonly used treatment for breast cancer, has been found safe and effective in studies. Most patients tolerate it well, and any side effects are typically mild.

Both treatments have demonstrated safety for patients with advanced breast cancer, based on research and current use. Always consult your healthcare provider about any concerns before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about AZD9833 because it offers a fresh approach to treating advanced breast cancer. Unlike current treatments like fulvestrant, AZD9833 is designed as an oral selective estrogen receptor degrader (SERD). This means it not only blocks estrogen receptors but also helps degrade them, potentially making it more effective in stopping cancer growth. This new mechanism of action could provide a more convenient and potent option for patients, offering hope for improved outcomes in fighting advanced breast cancer.

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

Research has shown that AZD9833, also known as camizestrant, is a promising treatment for advanced breast cancer. In this trial, participants will receive either AZD9833 at varying doses or Fulvestrant, a common treatment. Studies have found that AZD9833 can slow the disease more effectively than Fulvestrant. Specifically, camizestrant has been linked to longer periods where the cancer does not worsen. This oral medication works by blocking and breaking down estrogen receptors, which many breast cancers need to grow. These findings suggest AZD9833 may be an effective option for managing advanced breast cancer. ^{4 6 7 8 9}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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 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 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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04588298

NCT04588298 | A Study to Investigate the Biological ... The PD effect of AZD9833 on ER expression comparing pre- and on-treatment tumour samples in women with early breast cancer after 5 to 7 days and 12 to 15 days ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.1024

A phase I dose escalation and expansion study of the next ... The primary objective is to determine the safety and tolerability of AZD9833 once daily (QD), with dose-limiting toxicities (DLTs) in 28d ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10690091/

The Next-Generation Oral Selective Estrogen Receptor ... Our results support camizestrant's potential to be a superior backbone ET in naïve, early-stage disease, as well as in late-stage ER+/HER2− breast cancer tumors ...

4. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(24)00387-5/abstract

Camizestrant, a next-generation oral SERD, versus ... Camizestrant at 75 and 150 mg showed a significant benefit in progression-free survival versus fulvestrant. These results support further ...

5. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)00138-8/fulltext

SERENA-1 monotherapy results Camizestrant (AZD9833) is a next-generation oral SERD and pure ER antagonist, currently in phase III development for treating patients with HR+, ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04214288

NCT04214288 | A Study to Investigate Efficacy and Safety ... The safety and tolerability of AZD9833 when compared to fulvestrant in women with advanced ER-positive HER2-negative breast cancer was evaluated. From the date ...

7. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D8530C00002

A study to investigate efficacy and safety with oral ... This study is randomized, open-label, parallel-group, multicentre Phase 2 study aimed to compare the efficacy and safety of oral AZD9833 versus intramuscular ( ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38729567/

A phase I dose escalation and expansion trial of the next- ... Camizestrant is a next-generation oral selective ER antagonist and degrader (SERD) and pure ER antagonist with a tolerable safety profile.

9. clinicaltrials.gov clinicaltrials.gov/study/NCT03616587

NCT03616587 | Study of AZD9833 Alone or in ... This is a multicentre dose escalation and expansion, first-in-human study designed to evaluate the safety and tolerability of AZD9833, alone (Parts A and B) ...