A Phase IIIb Single Arm, 2 Cohorts Study Assessing the Efficacy and Safety of Capivasertib+ Fulvestrant as Treatment for Locally Advanced(Inoperable) or Metastatic Hormone Receptor Positive, Human Epidermal Growth Factor Receptor 2 Negative (HR+/HER2-) Breast Cancer Following Recurrence or Progression On or After Treatment With Endocrine Therapy in Chinese Patients

Plain English Summary

Capivasertib+Fulvestrant asTreatment for Locally Advanced(Inoperable) or Metastatic HR+/HER2- Breast Cancer in Chinese Patients is a Phase 3 clinical trial sponsored by AstraZeneca studying Breast Cancer. This study tests the combination of Capivasertib and Fulvestrant in patients with advanced or metastatic hormone-receptor-positive, HER2-negative breast cancer. It is for Chinese patients whose cancer has returned or grown after prior endocrine therapy. Participation involves taking oral Capivasertib and receiving Fulvestrant, with regular monitoring and assessments. Alternative treatments may include other endocrine therapies, chemotherapy, or targeted therapies, depending on the patient's specific situation and prior treatments. The trial aims to enroll 258 participants.

Official Summary

This is a multi-center, two-cohorts, phase IIIb study of Capivasertib+Fulvestrant in HR+/HER2-ABC who had disease recurrence/progression following 1-2L endocrine therapy. The Primary objective is to assess the efficacy of capi+ful by assessment of TFST (Time to first subsequent treatment) of PIK3CA/AKT1/PTEN-altered subgroup in cohort1.

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults aged 18 and older with confirmed HR+/HER2- breast cancer that is locally advanced (inoperable) or has spread to other parts of the body. Patients must have experienced cancer recurrence or progression during or within 12 months after endocrine therapy. Individuals with specific genetic alterations (PIK3CA/AKT1/PTEN) in their tumor are required for one of the study cohorts. Patients with rapidly progressing or life-threatening disease, or those with other recent cancer treatments, may not be eligible. This trial is studying Breast Cancer, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures how long patients can avoid starting another cancer treatment, indicating how effective the study drugs are in controlling the cancer. The specific primary outcome measures are: Time to first subsequent treatment (TFST) of PIK3CA/AKT1/PTEN-altered population in Cohort 1 (From the first dose of study intervention to the earlier of start date of the first subsequent therapy after discontinuation of study intervention, or death in PIK3CA/AKT1/PTEN-altered population in Cohort 1, up to approximately 2 years). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial addresses a critical need for new treatments for patients with advanced HR+/HER2- breast cancer who have progressed on standard endocrine therapy, potentially offering a new option for this As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Breast Cancer, where improved treatment options are needed.

Investor Insight

This Phase IIIb study by AstraZeneca targets a significant market of breast cancer patients with limited treatment options after progression on endocrine therapy, aiming to demonstrate the efficacy of Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage.

Is This Trial Right for Me?

Ask your doctor if your cancer has the specific genetic alterations (PIK3CA/AKT1/PTEN) being studied and if this trial is a suitable option for you. Be prepared for regular clinic visits for assessments, blood tests, and receiving the study medications. Understand that you will need to provide a tumor sample for genetic testing and may need to continue LHRH agonist treatment if you are a pre-menopausal woman. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NON_RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 258 participants

Interventions

• DRUG: Capivasertib — 400 mg, oral, twice daily; 4 days on and 3 days off
• DRUG: Fulvestrant — Fulvestrant IV

Primary Outcomes

• Time to first subsequent treatment (TFST) of PIK3CA/AKT1/PTEN-altered population in Cohort 1 (From the first dose of study intervention to the earlier of start date of the first subsequent therapy after discontinuation of study intervention, or death in PIK3CA/AKT1/PTEN-altered population in Cohort 1, up to approximately 2 years)

Secondary Outcomes

• Progression-free survival (PFS) in PIK3CA/AKT1/PTEN-altered population in Cohort 1 and 2 (From first dose until objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from study treatment or receives another anti-cancer therapy before progression, up to 2 years)
• Time to first subsequent treatment (TFST) in PIK3CA/AKT1/PTEN-altered population in Cohort 2 (From the first dose of study intervention to the earlier of start date of the first subsequent therapy after discontinuation of study intervention, or death in PIK3CA/AKT1/PTEN-altered population in Cohort 2, up to approximately 2 years)
• Number of participants with AEs/SAEs (From time of signature of the ICF, throughout the treatment period and including the 30-day follow-upperiod after discontinuation of study drug, up to approximately 2 years)
• Objective response rate (ORR) in PIK3CA/AKT1/PTEN-altered population in Cohort 1 and 2 (The percentage of PIK3CA/AKT1/PTEN-altered subjects with at least one investigator-assessed response of CR or PR and will be based on a subset of all PIK3CA/AKT1/PTEN-altered subjects with measurable disease at baseline per the site investigator.)
• Number of participants with AEs/SAEs in PIK3CA/AKT1/PTEN-altered population (From time of signature of the ICF, throughout the treatment period and including the 30-day follow-upperiod after discontinuation of study drug in PIK3CA/AKT1/PTEN-altered population, up to approximately 2 years)

Full Eligibility Criteria

Inclusion Criteria

1. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the clinical study protocol (CSP).
2. Provision of signed and dated, written ICF prior to any mandatory study specific procedures, sampling, and analyses.
3. Patients must be aged ≥18 years at the time of signing the ICF
4. Adult females, pre- and/or post-menopausal, and adult males -Pre-menopausal (and peri-menopausal i.e., those that do not meet the criteria for post-menopausal defined below) women can be enrolled if amenable to treatment with an LHRH agonist. Patients are to have commenced concomitant treatment with LHRH agonist prior to or on Cycle 1, Day 1 and must be willing to continue on it for the duration of the study -Post-menopausal women are defined as: a)aged ≥60 years of age, or b)aged \<60 years of age and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments/chemotherapy/ovarian suppression/tamoxifen or similar. These patients should also have serum oestradiol and follicle stimulating hormone (FSH) levels confirmed as being within the standard laboratory reference range for post-menopausal females, or c)documented bilateral oophorectomy
5. Histologically confirmed HR+/HER2- breast cancer determined from the most recent tumour sample (primary or metastatic), as per the American Society of Clinical Oncology and College of American Pathologists guideline recommendations. To fulfil the requirement of HR+ disease, a breast cancer must express ER with or without co-expression of progesterone receptor. 1)ER+ defined as ≥1% of tumour cells stain positive for ER on immunohistochemistry (IHC) or, if no percentage is available, then an Allred IHC score of ≥3/8, 2)Progesterone receptor positive defined as ≥1% of tumour cells stain positive for progesterone receptor on IHC or, if no percentage is available, then an Allred IHC score of ≥3/8; or progesterone receptor negative defined as \<1% of tumour cells stain positive for progesterone receptor on IHC or, if no percentage is available, then an Allred IHC score of ≤2/8; or progesterone receptor unknown, 3)or the investigator assesses the condition as HR+ status and 4)HER2- defined as 0 or 1+ intensity on IHC, or 2+ intensity on IHC and no evidence of amplification on in situ hybridisation (ISH), or if IHC not done, no evidence of amplification on ISH.

   Metastatic or locally advanced disease with radiographic or objective evidence of recurrence or progression (cancer that has progressed during or after a recent treatment period).; locally advanced disease must not be amenable to resection with curative intent (patients who are considered suitable for surgical or ablative techniques following potential down-staging with study treatment are not eligible) Patients are to have received treatment with an endocrine therapy containing regimen (single agent or in combination) and have: a)Radiological evidence of breast cancer recurrence or progression during treatment or within 12 months after the end of treatment with a neoadjuvant or adjuvant endocrine therapy, OR b)Radiological evidence of progression while on prior ET administered as a treatment line for locally advanced or metastatic breast cancer (this does not need to be the most recent therapy) (for patients with breast cancer recurrence or progression while on, or within 12 months of the end of (neo)adjuvant treatment with an ET will be limited to approximately 10%).
6. Patients must have at least 1 measurable lesion.
7. Patients must be eligible for fulvestrant therapy as per local investigator assessment.
8. Consent to submit and provide a mandatory FFPE tumour sample for central testing.
9. Patients must be able to swallow and retain oral medication.
10. Eastern Cooperative Oncology Group (ECOG)/ World Health Organisation (WHO) performance status 0 or 1 and life expectancy of ≥12 weeks.
11. Patients with PIK3CA/AKT1/PTEN alterations confirmed by central laboratory NGS testing. (Note: Applicable exclusively to patients enrolled under Protocol Version 2.0.)

Exclusion Criteria

1. A disease burden that makes the patient ineligible for endocrine therapy per the investigator's best judgement (e.g., symptomatic visceral disease that is potentially life-threatening in the short-term)
2. History of another primary malignancy except for malignancy treated with curative intent with no known active disease ≥2 years before the first dose of study intervention and of low potential risk for recurrence. Exceptions include adequately resected non-melanoma skin cancer and curatively treated in situ disease. Radiotherapy within 2 weeks prior to the first dose of study intervention. Major surgery (excluding placement of vascular access) within 4 weeks prior to study treatment initiation
3. With the exception of alopecia, any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the t

Trial Locations

• Research Site, Baoding, China
• Research Site, Beijing, China
• Research Site, Beijing, China
• Research Site, Beijing, China
• Research Site, Beijing, China
• Research Site, Bengbu, China
• Research Site, Changchun, China
• Research Site, Changsha, China
• Research Site, Changsha, China
• Research Site, Changsha, China
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Breast Cancer
• Hormone Receptor Positive Breast Cancer
• HER2 Negative Breast Cancer
• Metastatic Breast Cancer
• Locally Advanced Breast Cancer
• Endocrine Therapy Resistance
• PIK3CA Alterations
• AKT1 Alterations
• PTEN Alterations
• Oncology

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