Camizestrant for Breast Cancer

(CAMBRIA-2 Trial)

Recruiting at 623 trial locations

Overseen By AstraZeneca Breast Cancer Study Locator Service

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must not be taking: SERDs, Fulvestrant, LHRH agonists

Disqualifiers: Metastatic cancer, Heart failure, others

Stay on Your Current Meds You can continue your current medications while participating

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: 7 years

5500 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a Phase III open-label study to assess if camizestrant improves outcomes compared to standard adjuvant endocrine therapy for patients with ER+/HER2- early breast cancer with intermediate-high or high risk for disease recurrence who completed definitive locoregional therapy (with or without chemotherapy). The planned duration of treatment in either arm within the study will be 7 years.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot take certain hormone therapies or anti-cancer treatments not mentioned in the protocol, except for bisphosphonates or RANKL inhibitors.

What data supports the effectiveness of the drug Camizestrant for breast cancer?

Research shows that Camizestrant, an oral drug, significantly extends the time patients live without their cancer getting worse compared to the standard treatment, fulvestrant, in women with advanced estrogen receptor-positive breast cancer. It also works well in patients who have certain genetic mutations or have previously been treated with other cancer drugs. ^{1 2 3 4 5}

Is camizestrant safe for humans?

Camizestrant has been studied in clinical trials for breast cancer, and while the focus has been on its effectiveness, these trials also monitor safety. In the SERENA-6 trial, safety is a secondary endpoint, indicating that researchers are actively assessing its safety profile in humans. ^{1 2 3 4 6}

How is the drug camizestrant unique for treating breast cancer?

Camizestrant is a next-generation oral selective estrogen receptor degrader (SERD) that offers a novel approach by significantly prolonging progression-free survival in estrogen receptor-positive, HER2-negative breast cancer compared to standard treatments like fulvestrant. It is particularly effective in patients with ESR1 mutations and those who have developed resistance to other therapies, such as CDK4/6 inhibitors. ^{1 2 3 7 8}

Eligibility Criteria

This trial is for adults with ER+/HER2- early-stage breast cancer that's been surgically removed, without signs of spreading. They should have finished primary treatment and can join within a year of surgery. Prior short-term endocrine therapy is okay. Participants need to be in good health with proper organ function.

Inclusion Criteria

My breast cancer is early-stage, ER+ and HER2-, with no signs of spreading.

I have completed treatment for my breast cancer, including surgery and possibly chemotherapy.

My organs and bone marrow are working well.

Exclusion Criteria

My breast cancer cannot be removed by surgery and has spread.

I am currently on hormone therapy for conditions not related to cancer.

I have been cancer-free for at least 5 years, except for certain low-risk types.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive camizestrant or standard endocrine therapy with or without abemaciclib for 7 years

7 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

10 years

Treatment Details

Interventions

• Camizestrant

Trial Overview The study compares the effectiveness of Camizestrant against standard adjuvant endocrine therapies like Tamoxifen, Anastrozole, Letrozole, Exemestane, or Abemaciclib over 7 years in preventing breast cancer recurrence after initial treatment.

Participant Groups

Group I: Arm B: camizestrant ± abemaciclib Experimental Treatment 2 Interventions

camizestrant ± abemaciclib

Group II: Arm A: standard endocrine therapy of investigator´s choice ± abemaciclib Active Control 5 Interventions

standard endocrine therapy of investigator's choice (aromatase inhibitors \[AI; exemestane, letrozole, anastrozole\] or tamoxifen) ± abemaciclib

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

Austrian Breast and Colorectal Cancer Study Group (ABCSG)

Collaborator

Trials

1

Recruited

5,500+

Findings from Research

The phase II SERENA-2 trial indicates that camizestrant, an investigational oral selective estrogen receptor degrader, significantly prolongs progression-free survival compared to standard treatment with fulvestrant in postmenopausal women with advanced estrogen receptor-positive, HER2-negative breast cancer.

Camizestrant showed superior efficacy in specific patient subgroups, including those who had previously received a CDK4/6 inhibitor, had visceral metastases, or had ESR1 mutations, suggesting it may be particularly beneficial for these populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Second Oral SERD Shines in ER+ Breast Cancer. [2023]

Camizestrant, an oral selective estrogen receptor degrader (SERD), shows strong antitumor activity in estrogen receptor-positive (ER+) breast cancer, effectively degrading the estrogen receptor and inhibiting cancer cell growth in both wild-type and mutant models.

When combined with CDK4/6 inhibitors and PI3K/AKT/mTOR-targeted therapies, camizestrant enhances antitumor effects, making it a promising option for overcoming resistance to current endocrine therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Next-Generation Oral Selective Estrogen Receptor Degrader Camizestrant (AZD9833) Suppresses ER+ Breast Cancer Growth and Overcomes Endocrine and CDK4/6 Inhibitor Resistance. Lawson, M., Cureton, N., Ros, S., et al.[2023]

The SERENA-6 study is investigating the effectiveness of camizestrant, a next-generation oral selective estrogen receptor degrader, in patients with hormone-receptor-positive advanced breast cancer who have developed ESR1 mutations, which often lead to resistance against standard therapies.

The study aims to switch patients from aromatase inhibitors to camizestrant upon detecting ESR1 mutations in circulating tumor DNA, with the goal of improving progression-free survival and delaying the need for chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design of SERENA-6, a phase III switching trial of camizestrant in ESR1-mutant breast cancer during first-line treatment. Turner, N., Huang-Bartlett, C., Kalinsky, K., et al.[2023]

In the FLIPPER trial, the combination of palbociclib and fulvestrant significantly improved progression-free survival (PFS) in postmenopausal women with HR+/HER2- advanced breast cancer compared to placebo and fulvestrant.

Patient-reported outcomes indicated that while global health status and quality of life (QoL) were maintained during treatment with palbociclib/fulvestrant, the time to deterioration in QoL was longer with placebo/fulvestrant, suggesting that palbociclib/fulvestrant is a beneficial treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality of life with palbociclib plus fulvestrant versus placebo plus fulvestrant in postmenopausal women with endocrine-sensitive hormone receptor-positive and HER2-negative advanced breast cancer: patient-reported outcomes from the FLIPPER trial. Tibau, A., Martínez, MT., Ramos, M., et al.[2023]

Capivasertib, when added to fulvestrant, significantly improves progression-free survival (10.3 months vs. 4.8 months) and overall survival (29.3 months vs. 23.4 months) in women with aromatase inhibitor-resistant ER-positive, HER2-negative advanced breast cancer, based on a study of 140 participants.

The treatment appears to be particularly effective in patients with tumors that have alterations in the PI3K/AKT/PTEN pathway, showing a median progression-free survival of 12.8 months compared to 4.6 months for those receiving placebo in this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic, oestrogen receptor-positive, HER2-negative breast cancer (FAKTION): overall survival, updated progression-free survival, and expanded biomarker analysis from a randomised, phase 2 trial. Howell, SJ., Casbard, A., Carucci, M., et al.[2022]

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]

Capivasertib is a novel AKT inhibitor that has shown promising efficacy in treating breast cancer, particularly in tumors with specific genetic alterations, and is more effective when combined with other treatments like paclitaxel and fulvestrant.

The recommended dosing schedule for capivasertib is 480 mg twice daily for four days followed by three days off, with manageable side effects including hyperglycemia and diarrhea, indicating a favorable safety profile for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

"The emerging role of capivasertib in breast cancer". Andrikopoulou, A., Chatzinikolaou, S., Panourgias, E., et al.[2022]

Capivasertib, an oral AKT inhibitor, was well tolerated when combined with weekly paclitaxel in patients with advanced ER+/HER2- breast cancer, with a recommended dosing schedule of 400 mg twice daily for 4 days on and 3 days off.

However, the addition of capivasertib did not significantly improve progression-free survival compared to placebo, with median PFS of 10.9 months for capivasertib versus 8.4 months for placebo in the overall population, indicating it may not enhance treatment outcomes in this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BEECH: a dose-finding run-in followed by a randomised phase II study assessing the efficacy of AKT inhibitor capivasertib (AZD5363) combined with paclitaxel in patients with estrogen receptor-positive advanced or metastatic breast cancer, and in a PIK3CA mutant sub-population. Turner, NC., Alarcón, E., Armstrong, AC., et al.[2023]

References

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

Second Oral SERD Shines in ER+ Breast Cancer. [2023]

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

The Next-Generation Oral Selective Estrogen Receptor Degrader Camizestrant (AZD9833) Suppresses ER+ Breast Cancer Growth and Overcomes Endocrine and CDK4/6 Inhibitor Resistance. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Design of SERENA-6, a phase III switching trial of camizestrant in ESR1-mutant breast cancer during first-line treatment. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Quality of life with palbociclib plus fulvestrant versus placebo plus fulvestrant in postmenopausal women with endocrine-sensitive hormone receptor-positive and HER2-negative advanced breast cancer: patient-reported outcomes from the FLIPPER trial. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic, oestrogen receptor-positive, HER2-negative breast cancer (FAKTION): overall survival, updated progression-free survival, and expanded biomarker analysis from a randomised, phase 2 trial. [2022]

6. 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]

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

"The emerging role of capivasertib in breast cancer". [2022]

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

BEECH: a dose-finding run-in followed by a randomised phase II study assessing the efficacy of AKT inhibitor capivasertib (AZD5363) combined with paclitaxel in patients with estrogen receptor-positive advanced or metastatic breast cancer, and in a PIK3CA mutant sub-population. [2023]