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Evaluating capivasertib and fulvestrant for advanced breast cancer in Spain

A Phase IIIB Study to Evaluate the Use of Capivasertib in Combination With Fulvestrant in Patients With HR+ / HER2- Advanced Breast Cancer Who Have Relapsed/Progressed on ET and CDK4/6 Inhibitor Reflecting Real World Clinical Practice in Spain

PHASE3 · AstraZeneca · NCT06764186

This study is testing if a new drug called capivasertib, combined with fulvestrant, can help people with advanced breast cancer that hasn't improved after other treatments.

Quick facts

PhasePHASE3
Study typeInterventional
Enrollment100 (estimated)
Ages18 Years to 130 Years
SexAll
SponsorAstraZeneca (industry)
Drugs / interventionschemotherapy
Locations18 sites (Alicante and 17 other locations)
Trial IDNCT06764186 on ClinicalTrials.gov

What this trial studies

This Phase IIIB study aims to assess the effectiveness and safety of capivasertib in combination with fulvestrant for patients with locally advanced or metastatic HR+/HER2- breast cancer that has progressed after endocrine therapy and CDK4/6 inhibitors. The study will be conducted across multiple centers in Spain and will involve administering capivasertib at a dose of 400mg twice daily for four days followed by three days off, alongside fulvestrant at a monthly dose of 500mg. The focus is on patients with specific genetic alterations in the PIK3CA/AKT1/PTEN pathways, reflecting real-world clinical practice.

Who should consider this trial

Good fit: Ideal candidates include patients with HR+/HER2- breast cancer who have experienced disease progression after prior endocrine therapy and CDK4/6 inhibitors and have specific genetic alterations.

Not a fit: Patients who do not have the required PIK3CA/AKT1/PTEN alterations or those with HER2-positive breast cancer will likely not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment combination could provide a new therapeutic option for patients with advanced breast cancer who have limited treatment alternatives.

How similar studies have performed: Other studies have shown promising results with similar combinations targeting the PIK3CA/AKT1/PTEN pathways, indicating potential for success in this approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
Key Inclusion Criteria

Histologically confirmed HR+/HER2- breast cancer (primary or metastatic):

* HR+ defined as ER+ with or without PRg+
* HER2- defined as IHC 0 or 1+, or IHC 2+/ISH-

Patient with tumours harbouring at least one PIK3CA/AKT1/PTEN qualifying alteration detected in tissue, using a NGS test acceptable by the conditions included in the SmPC.

Metastatic or locally advanced disease with radiological or objective evidence of recurrence or progression.

Patients must have received treatment with an ET in combination with CDK4/6i and have:

* Radiological evidence of breast cancer recurrence or progression while on, or within 12 months of the end of (neo)adjuvant treatment with an ET with CDK4/6i, OR
* Radiological evidence of progression while on prior ET with CDK4/6i administered as a treatment line for locally advanced or metastatic breast cancer.

Informed consent

Eastern Cooperative Oncology Group (ECOG)/ World Health Organisation (WHO) performance status ≤ 2 at enrollment (not more than 20% of patients with ECOG PS2 will be allowed).

Reproduction:

* Women of childbearing potential (WOCBP) patients with ovarian suppression induced by LHRH agonist should agree to use 2 forms of highly effective methods of accepted contraception to prevent pregnancy.
* Male patients should use barrier contraception.

Key Exclusion Criteria

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.

Disease burden making the patient ineligible for endocrine therapy per the investigator judgement.

Unresolved toxicities from prior therapy greater than CTCAE grade 1.

Leptomeningeal metastases or symptomatic, unstable, or steroid-dependent brain metastases.

HbA1c ≥8.0% (63.9 mmol/mol).

Inadequate bone marrow reserve or organ function.

Severe or uncontrolled systemic diseases, uncontrolled hypertension, active infections including hepatitis B, hepatitis C, HIV, and confirmed COVID-19.

Known abnormalities in coagulation.

Refractory nausea, vomiting, malabsorption syndrome, chronic gastrointestinal diseases, inability to swallow formulated product, or significant bowel resection.

Previous allogenic bone marrow or solid organ transplant.

Known immunodeficiency syndrome.

Unknown or non-altered PIK3CA/AKT1/PTEN-status.

Evidence of dementia altered mental status or any psychiatric condition.

Pregnant women.

Participants with significant QT interval prolongation or a history of related cardiac conditions, including arrhythmias or recent cardiac procedures.

Prior/concomitant therapy:

* More than 2 lines of endocrine therapy or in combination with CDK4/6i for inoperable locally advanced or metastatic disease.
* More than 1 line of chemotherapy for inoperable locally advanced or metastatic disease. Adjuvant and neoadjuvant chemotherapy are not classed as lines of chemotherapy for ABC.

AKT1, PIK3CA and mTOR inhibitors not allowed.

Adequate washout or dose reduction may be required for some CYP3A.

Participation in another clinical study with a study intervention.

Where this trial is running

Alicante and 17 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Locally Advanced or Metastatic Breast Cancer, Luminal, PIK3CA/AKT1/PTEN, PI3K/AKT pathway, capivasertib, HR+ / HER2-, fulvestrant

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.