Camizestrant for Early Breast Cancer

(CAMBRIA-1 Trial)

Recruiting at 580 trial locations

Overseen By AstraZeneca Breast Cancer Study Locator Service

Age: 18+

Sex: Any

Trial Phase: Phase 3

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 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: 60 months

4300 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a new drug, camizestrant, can improve outcomes for people with early-stage breast cancer. It targets those with estrogen receptor-positive (ER+) and HER2-negative breast cancer at intermediate or high risk of recurrence. Participants should have completed surgery and possibly chemotherapy, along with at least two years of hormone therapy. The trial compares camizestrant with standard hormone treatments to determine which is more effective over five years. Ideal candidates have completed their initial cancer treatments and are concerned about recurrence. As a Phase 3 trial, this study is the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

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

Research has shown that camizestrant is generally well-tolerated. It targets and breaks down estrogen receptors, proteins that can promote the growth of some breast cancers. This makes it a potential treatment for certain types of breast cancer that rely on estrogen.

In earlier trials, most patients did not experience severe side effects. Some reported mild to moderate effects like nausea or tiredness, common with many cancer treatments. No new or unexpected safety issues emerged.

Testing camizestrant in a late-stage trial indicates it has demonstrated a reasonable safety profile in earlier studies. If successful, it could become an important option for patients with early breast cancer. ^{1 2 3 4 5}

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

Unlike the standard breast cancer treatments that involve aromatase inhibitors or tamoxifen, camizestrant offers a fresh approach by being a selective estrogen receptor degrader (SERD). This means it targets estrogen receptors more directly, potentially leading to more effective blocking of the hormone's cancer-fueling effects. Researchers are excited about camizestrant because it may overcome resistance seen with current hormone therapies, offering new hope for improved outcomes in early breast cancer.

What evidence suggests that camizestrant might be an effective treatment for early breast cancer?

Research has shown that camizestrant, also known as AZD9833, could be a promising treatment for early breast cancer. It blocks and breaks down estrogen receptors, proteins that help some breast cancers grow. This action stops cancer cells from growing and surviving. Early studies demonstrated that camizestrant is safe for patients and has manageable side effects. In this trial, participants will receive either camizestrant or standard endocrine therapy chosen by the investigator. The goal is to determine if camizestrant can lead to better results compared to standard hormone treatments. ^{4 5 6 7 8}

Are You a Good Fit for This Trial?

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Camizestrant

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. 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.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04711252

NCT04711252 | A Comparative Study of AZD9833 Plus ... The trial drugs palbociclib, camizestrant, and anastrozole are designed to work by blocking the cancer's ability to grow. Camizestrant is also called AZD9833.

3. hemonc.org hemonc.org/wiki/Camizestrant_(AZD-9833)

Camizestrant (AZD-9833) This prevents ER-mediated signaling and inhibits the growth and survival of ER-expressing cancer cells. Preliminary data. Note: This is not meant to be an ...

4. synapse.patsnap.com synapse.patsnap.com/drug/abaebfc198c3417f8fe7111251174ab3

Camizestrant - Drug Targets, Indications, Patents 10,11 Once patients are diagnosed with metastatic disease, the five-year survival rate drops from nearly 90% to approximately 30%.12 New ...

5. ufhealth.org ufhealth.org/clinical-trials/an-adjuvant-endocrine-based-therapy-study-of-camizestrant-azd9833-in-er-her2-early-breast-cancer

An Adjuvant Endocrine-based Therapy Study of ... 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* ...

6. pubchem.ncbi.nlm.nih.gov pubchem.ncbi.nlm.nih.gov/compound/Camizestrant

Camizestrant | C24H28F4N6 | CID 134453496 - PubChem - NIH Camizestrant is an orally available selective estrogen receptor degrader (SERD), with potential antineoplastic activity.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04588298

NCT04588298 | A Study to Investigate the Biological ... This is a randomised, open-label, parallel-group, pre-surgical study aimed to investigate the biological effects, safety, tolerability, and pharmacokinetics ( ...

8. go.drugbank.com go.drugbank.com/drugs/DB19218

Camizestrant: Uses, Interactions, Mechanism of Action Camizestrant is under investigation in clinical trial NCT05952557 (An Adjuvant Endocrine-based Therapy Study of Camizestrant (AZD9833) in ER+/ ...