AZD9833 + Palbociclib for Breast Cancer

(SERENA-4 Trial)

Not currently recruiting at 315 trial locations

Overseen By AZ Breast Cancer Study Navigators

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must be taking: LHRH agonists

Must not be taking: SERDs, Fulvestrant

Disqualifiers: CNS metastases, Heart 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: Unknown

Duration: Until disease progression or withdrawal

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for advanced breast cancer. Researchers aim to determine if camizestrant (AZD9833), when combined with palbociclib, is more effective than the current standard treatment of anastrozole with palbociclib. The study targets participants with breast cancer that has either metastasized or recurred after at least two years following standard hormone treatment. It is suitable for those with ER-positive, HER2-negative cancer who have not yet received systemic treatment for advanced cancer. Participants should be capable of performing daily activities and free from major health issues that could interfere with the trial. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to a treatment that could soon become widely available.

Will I have to stop taking my current medications?

The trial requires a 2-week period without taking tamoxifen before starting. If you're on other cancer treatments or medications affecting certain proteins, you may need to stop them, but the protocol doesn't specify all medications.

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

Research shows that the combination of AZD9833 (also known as camizestrant) with palbociclib is generally well-tolerated. An earlier study using the same dose of camizestrant as in this trial found that most participants did not experience severe side effects when combined with palbociclib.

Palbociclib is already known to enhance the effectiveness of other cancer treatments while keeping side effects manageable.

These findings suggest that using AZD9833 and palbociclib together is generally safe. However, as with any treatment, some individuals may still experience side effects. Overall, the evidence supports the safety of these drugs when used together. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for breast cancer?

Unlike the standard treatments for breast cancer, which often involve hormone blockers like anastrozole, the investigational drug AZD9833 works by targeting estrogen receptors directly. This new mechanism could offer a more precise approach to blocking the cancer's growth. Researchers are excited because combining AZD9833 with palbociclib might enhance the effectiveness of treatment, offering new hope for better outcomes. Plus, by potentially reducing reliance on existing hormone therapies, this combination could also help manage side effects or resistance issues that some patients face with current options.

What evidence suggests that AZD9833 with palbociclib could be an effective treatment for advanced/metastatic breast cancer?

Studies have shown that combining palbociclib with an aromatase inhibitor like anastrozole can reduce the risk of breast cancer progression by about 30% in patients with advanced stages of the disease. In this trial, one group of participants will receive this combination of anastrozole and palbociclib. Previous research found that camizestrant (also known as AZD9833) combined with palbociclib was well tolerated, suggesting it could be a promising treatment. Another group in this trial will receive the combination of camizestrant with palbociclib, aiming for better results than the current standard treatment. This new combination seeks to be more effective, potentially offering better control over cancer progression. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for adults with ER-positive, HER2-negative advanced breast cancer who haven't had systemic treatment for their condition. Eligible participants include pre-/peri-menopausal women or men willing to take LHRH agonists and those with measurable disease or certain bone lesions. Exclusions apply to those with specific health issues, past treatments that failed within a year, or uncontrolled brain metastases.

Inclusion Criteria

I haven't received any systemic anti-cancer treatments for my ER+ recurrent or metastatic cancer.

My breast cancer cannot be treated with surgery or radiation.

My organs and bone marrow are working well.

Exclusion Criteria

My cancer has spread to my brain or spinal cord and is not under control.

I do not have an active infection like TB, hepatitis B, or hepatitis C.

I am currently on cancer treatment or taking drugs that affect body proteins.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either AZD9833 plus palbociclib or anastrozole plus palbociclib in 28-day cycles

Until disease progression or withdrawal

Several visits throughout the trial for health checks, blood samples, and tumor scans

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Anastrozole
• AZD9833
• Palbociclib

Trial Overview The study tests the effectiveness of AZD9833 combined with palbociclib against anastrozole plus palbociclib in treating advanced breast cancer. It aims to determine if the new combination is superior as an initial treatment option for patients who have not received prior systemic therapy.

How Is the Trial Designed?

Group I: AZD9833 + palbociclib Experimental Treatment 4 Interventions

The patients will receive AZD9833 (75 mg, PO, once daily) + palbociclib (PO, once daily, 125 mg for 21 consecutive days followed by 7 days off treatment) + anastrozole placebo (1 mg, PO, once daily)

Group II: Anastrozole + palbociclib Active Control 4 Interventions

The patients will recieve Anastrozole (1 mg, PO, once daily) + palbociclib (PO, once daily, 125 mg for 21 consecutive days followed by 7 days off treatment) + AZD9833 placebo (PO, once daily)

Anastrozole is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Arimidex for:

• Breast cancer
• Early breast cancer in postmenopausal women

Approved in United States as Arimidex for:

• Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer
• First-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer

Approved in Canada as Arimidex for:

• Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer
• Treatment of postmenopausal women with hormone receptor-positive advanced breast cancer

Approved in Japan as Arimidex for:

• Breast cancer

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

In the PALOMA-2 trial involving 666 postmenopausal women with ER+/HER2- advanced breast cancer, the combination of palbociclib and letrozole significantly improved progression-free survival compared to letrozole alone, with a hazard ratio of 0.58.

Neutropenia was the most common adverse event associated with palbociclib, occurring in 95.3% of patients, but it was mostly manageable through dose modifications and did not compromise treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib with Letrozole in Postmenopausal Women with ER+/HER2- Advanced Breast Cancer: Hematologic Safety Analysis of the Randomized PALOMA-2 Trial. Diéras, V., Harbeck, N., Joy, AA., et al.[2020]

Palbociclib is the first CDK4/6 inhibitor approved for treating estrogen receptor-positive, HER2-negative metastatic breast cancer, and it works by selectively inhibiting CDK4 and CDK6, enhancing the effects of anti-estrogens like letrozole and fulvestrant.

Clinical trials show that palbociclib significantly doubles the treatment efficacy of letrozole and fulvestrant while maintaining a manageable safety profile, positively impacting patients' quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety and efficacy of palbociclib in the treatment of metastatic breast cancer. Ettl, J., Harbeck, N.[2017]

In a study of 666 postmenopausal women with advanced breast cancer, Asian patients receiving palbociclib plus letrozole experienced a significantly longer progression-free survival (PFS) of 25.7 months compared to 13.9 months for those on placebo plus letrozole, indicating the efficacy of this combination treatment.

While hematologic toxicities like neutropenia were more common in Asian patients, they were manageable, and quality of life remained stable, suggesting that palbociclib plus letrozole is a safe and effective treatment option for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib Plus Letrozole as First-Line Therapy in Postmenopausal Asian Women With Metastatic Breast Cancer: Results From the Phase III, Randomized PALOMA-2 Study. Im, SA., Mukai, H., Park, IH., et al.[2023]

Oral palbociclib is an effective treatment for HR-positive, HER2-negative advanced or metastatic breast cancer, significantly prolonging progression-free survival when used with letrozole or fulvestrant in clinical trials involving postmenopausal women.

The most common side effect was neutropenia, which was manageable and rarely led to serious complications, indicating that palbociclib can be safely administered without significantly compromising its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib: A Review in HR-Positive, HER2-Negative, Advanced or Metastatic Breast Cancer. Kim, ES., Scott, LJ.[2022]

Palbociclib, an inhibitor of CDK4 and CDK6, was granted accelerated FDA approval for treating advanced breast cancer in postmenopausal women when combined with letrozole, based on a trial involving 165 patients that showed significant improvement in progression-free survival (PFS).

The trial demonstrated a nearly 50% reduction in the risk of disease progression for patients receiving the combination therapy compared to those on letrozole alone, although the most common side effect noted was neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval: Palbociclib for the Treatment of Postmenopausal Patients with Estrogen Receptor-Positive, HER2-Negative Metastatic Breast Cancer. Beaver, JA., Amiri-Kordestani, L., Charlab, R., et al.[2022]

Anastrozole is a potent and selective third-line aromatase inhibitor that offers a significant advancement in the treatment of hormone-sensitive breast cancer, particularly for postmenopausal women.

This review highlights anastrozole's biochemical properties and clinical efficacy, indicating its widespread use as a first- and second-line treatment option, potentially providing better outcomes and safety compared to traditional therapies like tamoxifen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anastrozole: pharmacological and clinical profile in postmenopausal women with breast cancer. Köberle, D., Thürlimann, B.[2018]

Anastrozole is as effective as tamoxifen for treating advanced breast cancer in postmenopausal women, showing a slightly higher objective response rate (21% vs. 17%) and a significant clinical benefit in 59% of patients compared to 46% for tamoxifen.

Anastrozole offers a significant advantage in time to progression (median of 11.1 months vs. 5.6 months for tamoxifen) and has a lower incidence of side effects, such as thromboembolic events and vaginal bleeding, making it a preferable first-line therapy option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anastrozole is superior to tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women: results of a North American multicenter randomized trial. Arimidex Study Group. Nabholtz, JM., Buzdar, A., Pollak, M., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04711252

NCT04711252 | A Comparative Study of AZD9833 Plus ... The goal of the study is to demonstrate superiority of AZD9833 over anastrozole in the context of combination with palbociclib in first line setting.

2. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D8532C00001

A comparative study of AZD9833 Plus Palbociclib Versus ... The goal of the study is to demonstrate superiority of AZD9833 over anastrozole in the context of combination with palbociclib in first line setting.

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.1032

Serena-1: Updated analyses from a phase 1 study (parts C/ ... Results: As of 9 September 2021, 25 patients had received camizestrant 75 mg QD in combination with palbociclib. Tolerability of the combination ...

4. asco.org asco.org/abstracts-presentations/ABSTRACT362378

Serena-1: Updated analyses from a phase 1 study (parts C ... Results: As of 9 September 2021, 25 patients had received camizestrant 75 mg QD in combination with palbociclib. Tolerability of the combination of camizestrant ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12280009/

Real-world effectiveness of palbociclib plus an aromatase ... In a large (n = 2888), heterogeneous population in the United States, palbociclib plus ET was associated with a 30% reduction in risk of disease ...

6. withpower.com withpower.com/trial/phase-3-breast-neoplasms-2021-085a7

AZD9833 + Palbociclib for Breast Cancer (SERENA-4 Trial) Clinical trials show that palbociclib significantly doubles the treatment efficacy of letrozole and fulvestrant while maintaining a manageable safety profile, ...