Camizestrant for Early Breast Cancer

(CAMBRIA-1 Trial)

Recruiting at534 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: AstraZeneca

Must be taking: Adjuvant endocrine therapy

Must not be taking: Exogenous hormones, Anti-cancer treatments

Disqualifiers: Metastatic cancer, Severe diseases, others

Stay on Your Current Meds

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing camizestrant, a drug that blocks estrogen, in patients with ER+/HER2- early breast cancer at medium to high risk of recurrence. The goal is to see if it works better than standard hormone treatments by stopping cancer cells from growing.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that you cannot take certain hormone therapies or anti-cancer treatments not specified in the protocol. It's best to discuss your current medications with the trial team.

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

Research shows that Camizestrant, an oral drug, significantly improved progression-free survival (the time during which the cancer does not get worse) compared to the standard treatment in women with advanced estrogen receptor-positive breast cancer. It also worked well in patients who had certain genetic mutations or had previously been treated with other cancer drugs. ^{1 2 3 4 5}

What makes the drug camizestrant unique for treating early breast cancer?

Camizestrant is a next-generation oral selective estrogen receptor degrader (SERD) that offers a novel approach by effectively degrading estrogen receptors, which can help overcome resistance to other endocrine therapies and CDK4/6 inhibitors in estrogen receptor-positive breast cancer. ^{1 3 4 6 7}

Research Team

Eligibility Criteria

This trial is for adults over 18 with ER+/HER2- early breast cancer at intermediate/high risk of recurrence, who've completed 2-5 years of standard endocrine therapy after surgery and possibly chemotherapy. They should be in good health with proper organ/marrow function and not have metastatic breast cancer or other severe diseases.

Inclusion Criteria

I finished my hormone therapy for cancer between 2 and 5 years ago.

My breast cancer is ER+ and HER2-, with a high or intermediate risk of coming back.

I have taken CDK4/6 inhibitors for 2 years as part of my previous treatment.

Exclusion Criteria

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 skin cancers or cervical carcinoma in situ.

Currently pregnant (confirmed with positive serum pregnancy test) or breastfeeding

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either camizestrant or standard endocrine therapy for 60 months

60 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 10 years

Treatment Details

Interventions

• Camizestrant (Selective Estrogen Receptor Degrader (SERD))

Trial Overview The study tests if camizestrant can improve outcomes compared to standard therapies like Tamoxifen, Anastrozole, Letrozole, or Exemestane in patients with certain types of early-stage breast cancer. Participants will receive treatment for up to five years to see which is more effective.

Participant Groups

Group I: Arm B: camizestrant Experimental Treatment 1 Intervention

Camizestrant

Group II: Arm A: standard endocrine therapy of investigator´s choice Active Control 4 Interventions

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

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

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]

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]

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]

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]

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 the FAKTION trial involving 140 postmenopausal women with advanced breast cancer, the addition of capivasertib to fulvestrant significantly improved progression-free survival, with a median of 10.3 months compared to 4.8 months for the placebo group, indicating its efficacy in this patient population.

While capivasertib showed promising results, it was associated with serious adverse events, including acute kidney injury and infections, highlighting the need for careful monitoring and further investigation in phase 3 trials.

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 breast cancer (FAKTION): a multicentre, randomised, controlled, phase 2 trial. Jones, RH., Casbard, A., Carucci, M., 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]

References

1. 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]

2. 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]

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

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

4. 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]

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. England pubmed.ncbi.nlm.nih.gov

Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic, oestrogen receptor-positive breast cancer (FAKTION): a multicentre, randomised, controlled, phase 2 trial. [2021]

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

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