Camizestrant for Breast Cancer
(CAMBRIA-2 Trial)
Recruiting in Palo Alto (17 mi)
+627 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: AstraZeneca
Must not be taking: SERDs, Fulvestrant, LHRH agonists
Disqualifiers: Metastatic cancer, Heart failure, others
Stay on Your Current Meds
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Breakthrough Therapy
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.
12345Is 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.
12346How 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.
12378Eligibility 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
I am 18 years old or older.
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.
+4 more
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.
+8 more
Trial 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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm B: camizestrant ± abemaciclibExperimental Treatment2 Interventions
camizestrant ± abemaciclib
Group II: Arm A: standard endocrine therapy of investigator´s choice ± abemaciclibActive Control5 Interventions
standard endocrine therapy of investigator's choice (aromatase inhibitors \[AI; exemestane, letrozole, anastrozole\] or tamoxifen) ± abemaciclib
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Research SiteYpsilanti, MI
Research SiteFort Wayne, IN
Research SiteFairfax, VA
Research SiteWest Palm Beach, FL
More Trial Locations
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Who Is Running the Clinical Trial?
AstraZenecaLead Sponsor
Austrian Breast and Colorectal Cancer Study Group (ABCSG)Collaborator
References
Second Oral SERD Shines in ER+ Breast Cancer. [2023]The first data from the phase II SERENA-2 trial look promising for the investigational oral selective estrogen receptor degrader camizestrant. Compared with standard fulvestrant, it significantly prolonged progression-free survival in postmenopausal women with advanced estrogen receptor-positive, HER2-negative breast cancer. Camizestrant also bested fulvestrant in subgroup analyses of patients who previously received a CDK4/6 inhibitor, had visceral metastases, or had ESR1 mutations.
The Next-Generation Oral Selective Estrogen Receptor Degrader Camizestrant (AZD9833) Suppresses ER+ Breast Cancer Growth and Overcomes Endocrine and CDK4/6 Inhibitor Resistance. [2023]Oral selective estrogen receptor degraders (SERD) could become the backbone of endocrine therapy (ET) for estrogen receptor-positive (ER+) breast cancer, as they achieve greater inhibition of ER-driven cancers than current ETs and overcome key resistance mechanisms. In this study, we evaluated the preclinical pharmacology and efficacy of the next-generation oral SERD camizestrant (AZD9833) and assessed ER-co-targeting strategies by combining camizestrant with CDK4/6 inhibitors (CDK4/6i) and PI3K/AKT/mTOR-targeted therapy in models of progression on CDK4/6i and/or ET. Camizestrant demonstrated robust and selective ER degradation, modulated ER-regulated gene expression, and induced complete ER antagonism and significant antiproliferation activity in ESR1 wild-type (ESR1wt) and mutant (ESR1m) breast cancer cell lines and patient-derived xenograft (PDX) models. Camizestrant also delivered strong antitumor activity in fulvestrant-resistant ESR1wt and ESR1m PDX models. Evaluation of camizestrant in combination with CDK4/6i (palbociclib or abemaciclib) in CDK4/6-naive and -resistant models, as well as in combination with PI3Kαi (alpelisib), mTORi (everolimus), or AKTi (capivasertib), indicated that camizestrant was active with CDK4/6i or PI3K/AKT/mTORi and that antitumor activity was further increased by the triple combination. The response was observed independently of PI3K pathway mutation status. Overall, camizestrant shows strong and broad antitumor activity in ER+ breast cancer as a monotherapy and when combined with CDK4/6i and PI3K/AKT/mTORi.
Design of SERENA-6, a phase III switching trial of camizestrant in ESR1-mutant breast cancer during first-line treatment. [2023]ESR1 mutation (ESR1m) is a frequent cause of acquired resistance to aromatase inhibitor (AI) plus cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i), which is a first-line therapy for hormone-receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC). Camizestrant is a next-generation oral selective estrogen receptor degrader (SERD) that in a phase II study significantly improved progression-free survival (PFS) over fulvestrant (also a SERD) in ER+/HER2- ABC. SERENA-6 (NCT04964934) is a randomized, double-blind, phase III study evaluating the efficacy and safety of switching from an AI to camizestrant, while maintaining the same CDK4/6i, upon detection of ESR1m in circulating tumor DNA before clinical disease progression on first-line therapy for HR+/HER2- ABC. The aim is to treat ESR1m clones and extend the duration of control of ER-driven tumor growth, delaying the need for chemotherapy. The primary end point is PFS; secondary end points include chemotherapy-free survival, time to second progression event (PFS2), overall survival, patient-reported outcomes and safety.
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]In the FLIPPER trial, palbociclib/fulvestrant significantly improved progression-free survival (PFS) compared with placebo/fulvestrant in postmenopausal women with HR+/HER2- advanced breast cancer (ABC).
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]Capivasertib, an AKT inhibitor, added to fulvestrant, was previously reported to improve progression-free survival in women with aromatase inhibitor-resistant oestrogen receptor (ER)-positive, HER2-negative advanced breast cancer. The benefit appeared to be independent of the phosphoinositide 3-kinase (PI3K)/AKT/phosphatase and tensin homologue (PTEN) pathway alteration status of tumours, as ascertained using assays available at the time. Here, we report updated progression-free survival and overall survival results, and a prespecified examination of the effect of PI3K/AKT/PTEN pathway alterations identified by an expanded genetic testing panel on treatment outcomes.
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]Label="PURPOSE">Fulvestrant, the first-in-class selective estrogen receptor (ER) degrader (SERD), is clinically effective in patients with ER+ breast cancer, but it has administration and pharmacokinetic limitations. Pharmacodynamic data suggest complete ER degradation is not achieved at fulvestrant's clinically feasible dose. This presurgical study (NCT03236974) compared the pharmacodynamic effects of fulvestrant with AZD9496, a novel, orally bioavailable, nonsteroidal, potent SERD, in treatment-naïve patients with ER+ HER2- primary breast cancer awaiting curative intent surgery.
"The emerging role of capivasertib in breast cancer". [2022]Over 50% of breast tumors harbor alterations in one or more genes of the phosphatidylinositol 3-kinase (PI3K) pathway including PIK3CA mutations (31%), PTEN loss (34%), PTEN mutations (5%) and AKT1 mutations (3%). While PI3K and mTOR inhibitors are already approved in advanced breast cancer, AKT inhibitors have been recently developed as a new therapeutic approach. Capivasertib (AZD5363) is a novel, selective ATP-competitive pan-AKT kinase inhibitor that exerts similar activity against the three AKT isoforms, AKT1, AKT2, and AKT3. Preclinical studies demonstrated efficacy of capivasertib in breast cancer cell lines as a single agent or in combination with anti-HER2 agents and endocrine treatment, especially in tumors with PIK3CA or MTOR alterations. Phase I/II studies demonstrated greater efficacy when capivasertib was co-administered with paclitaxel, fulvestrant in hormone receptor (HR)-positive, HER2-negative breast cancer or olaparib. The recommended phase II dose of capivasertib as monotherapy was 480 mg bid on a 4-days-on, 3-days-off dosing schedule. Toxicity profile proved to be manageable with hyperglycemia (20-24%), diarrhea (14-17%) and maculopapular rash (11-16%) being the most common grade ≥3 adverse events. Ongoing Phase III trials of capivasertib in combination with fulvestrant (CAPItello-291), CDK4/6 inhibitor palbociclib (CAPItello-292) and paclitaxel (CAPItello- 290) will better clarify the therapeutic role of capivasertib in breast cancer.
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]BEECH investigated the efficacy of capivasertib (AZD5363), an oral inhibitor of AKT isoforms 1-3, in combination with the first-line weekly paclitaxel for advanced or metastatic estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer, and in a phosphoinositide 3-kinase, catalytic, alpha polypeptide mutation sub-population (PIK3CA+).