AZD9833 + Palbociclib for Breast Cancer

(SERENA-4 Trial)

Recruiting at 260 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

1370 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is comparing two drug combinations to treat a specific type of advanced breast cancer. One combination includes a new drug called camizestrant, and the other includes anastrozole. Both combinations also use palbociclib. The goal is to see which combination works better at slowing down the cancer.

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.

What data supports the effectiveness of the drug combination AZD9833 + Palbociclib for breast cancer?

Palbociclib, when combined with letrozole, has been shown to significantly extend the time patients live without their cancer getting worse in women with advanced breast cancer. Anastrozole, another component of the treatment, is effective in treating hormone-sensitive breast cancer in postmenopausal women. ^{1 2 3 4 5}

Is the combination of AZD9833 and Palbociclib safe for humans?

Palbociclib, when used with other medications like letrozole, has been shown to be generally safe in humans, but it can cause side effects like neutropenia (a low level of white blood cells). Anastrozole, another name for AZD9833, is also used safely in treating breast cancer, but specific safety data for the combination of AZD9833 and Palbociclib is not detailed in the available research. ^{1 3 4 6 7}

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

The combination of AZD9833 and Palbociclib is unique because it combines a new type of drug (AZD9833) with Palbociclib, a CDK4/6 inhibitor, to target breast cancer cells in a novel way. This approach may offer a new option for patients who have become resistant to other treatments, potentially improving outcomes by using different mechanisms to stop cancer cell growth. ^{1 3 8 9 10}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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 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]

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]

References

1. France pubmed.ncbi.nlm.nih.gov

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

2. England pubmed.ncbi.nlm.nih.gov

Anastrozole: pharmacological and clinical profile in postmenopausal women with breast cancer. [2018]

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

FDA Approval: Palbociclib for the Treatment of Postmenopausal Patients with Estrogen Receptor-Positive, HER2-Negative Metastatic Breast Cancer. [2022]

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

Anastrozole versus tamoxifen treatment in postmenopausal women with endocrine-responsive breast cancer and tamoxifen-induced endometrial pathology. [2018]

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

Phase II, randomized trial to compare anastrozole combined with gefitinib or placebo in postmenopausal women with hormone receptor-positive metastatic breast cancer. [2018]

6. United States 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. [2022]

7. England 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. [2020]

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

Results of the phase IIa RADICAL trial of the FGFR inhibitor AZD4547 in endocrine resistant breast cancer. [2023]

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

The safety and efficacy of palbociclib in the treatment of metastatic breast cancer. [2017]

10. United States 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. [2023]