Clinical trial NCT06764186: A Phase IIIB Study to Evaluate the Use of Capivasertib in Combination With Fulvestrant in Patients With Advanced Breast Cancer Who Have Relapsed/Progressed on ET and CDK4/6 Inhibitor Reflecting Real World Clinical Practice in Spain
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Locally Advanced or Metastatic Breast Cancer
Keywords: Luminal
PIK3CA/AKT1/PTEN
PI3K/AKT pathway
capivasertib
HR+ / HER2-
fulvestrant
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Apices Soluciones S.L.
name: SOLTI Breast Cancer Research Group
First posted: 2025-01-08
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the effectiveness and safety of capivasertib + fulvestrant treatment administration in patients with locally advanced (inoperable) or metastatic HR+ / HER2- breast cancer with PIK3CA/AKT1/PTEN-altered following recurrence or progression on or after endocrine therapy and CDK4/6 inhibitor.

Detailed description: Phase IIIb, multicentre, single arm, Spain study assessing effectiveness/safety of capivasertib+fulvestrant in locally advanced (inoperable) or metastatic HR+/HER2- BC with the PIK3CA/AKT1/PTEN-altered following recurrence or progression on or after endocrine therapy and CDK4/6 inhibitor. Capivasertib will be administered as 400mg BD, 4 days on 3 days off in combination with fulvestrant at the approved dose of monthly 500mg (2 × 5mL IV), with an additional loading dose in Cycle 1.

Eligibility 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.

Primary outcomes:
measure: Time to next treatment (TTNT)
timeFrame: From start of date of first dose of capivasertib+fulvestrant treatment to date of the first subsequent anti-cancer therapy or death or up to within approximately 12 months after Last Subject Inclusion
Secondary outcomes:
measure: Number of patients with AEs.
timeFrame: From enrollment up to at least 30 days (+7 days) after last dose of capivasertib + fulvestrant treatment
measure: Time to first Subsequent Chemotherapy (TFSC)
timeFrame: From start of capivasertib+fulvestrant treatment to the first Subsequent Chemotherapy, death, withdrawal of consent or the end of study (approximately 24 months)
measure: Progression-free survival (PFS)
timeFrame: From date of first dose of Capivasertib + fulvestrant until date of disease progression, death, withdrawal of consent or the end of study (approximately 24 months)
measure: Objective Response Rate (ORR)
timeFrame: From start of capivasertib+fulvestrant treatment to progression/death or up to 6 months after Last Subject Inclusion
measure: Overall survival (OS)
timeFrame: From date of first dose of capivasertib + fulvestrant treatment until death, withdrawal of consent, or the end of the study (approximately 24 months).
measure: Number of patients with change in EORTC QLQ C30 and QLQ-BR42, respectively
timeFrame: From start of capivasertib+fulvestrant treatment to first dose of subsequent line of treatment/death or up to within approximately 12 months after Last Subject Inclusion
measure: Time to deterioration
timeFrame: From start of capivasertib+fulvestrant treatment to first dose of subsequent line of treatment/death or up to within approximately 12 months after Last Subject Inclusion
measure: Number of patients with change from in PGI-S
timeFrame: From start of capivasertib+fulvestrant treatment to the end of the study (approximately 24 months)
measure: Number of patients with change in PGI-II
timeFrame: From start of capivasertib+fulvestrant treatment to the end of the study (approximately 24 months)
measure: Number of patients with change in Daily bowel habits
timeFrame: From start of capivasertib+fulvestrant treatment to the end of the study (approximately 24 months)
measure: Number of patients with change in ADAQ
timeFrame: From start of capivasertib+fulvestrant treatment to the end of the study (approximately 24 months)
Other outcomes:
Locations:
city: Alicante
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Bilbao (Vizcaya)
country: Spain
facility: Research Site
city: Cáceres
country: Spain
facility: Research Site
city: Córdoba
country: Spain
facility: Research Site
city: Donostia
country: Spain
facility: Research Site
city: El Palmar
country: Spain
facility: Research Site
city: Girona
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Oviedo
country: Spain
facility: Research Site
city: Palma deMallorca
country: Spain
facility: Research Site
city: Salamanca
country: Spain
facility: Research Site
city: Santander
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Zaragoza
country: Spain
facility: Research Site
Study officials:
References: