Phase III Study to Evaluate the Safety, Efficacy, and Impact on Quality of Life of Capivasertib Alongside Standard-of-care Endocrine Treatment in Patients With HR+/HER2- Advanced Breast Cancer and Progression on Prior Endocrine-based Treatment

NCT07281833 | Recruiting Phase 3 DMC

• 1 other identifier: WSG-AM14 (CAPIcorn)
• Study Type: interventional
• Target: 250
• Locations: 3 countries
• Sites: 7

Brief Summary

This is a multicentre phase-III-trial to evaluate the use of capivasertib in patients with HR+/HER2- advanced breast cancer and progression on prior endocrine-based treatment. The goal of this study is

1. 1.To evaluate benefit of capivasertib regarding time to next treatment (TTNT1) - i.e., time "on treatment" with capivasertib.
2. 2.To evaluate the benefits of patient reported outcome(PRO)-adherence regarding the deterioration of quality of life (DQoL)-free interval.

Conditions

Breast Cancer; HR-positive Breast Cancer; Advanced Breast Cancer; Metastatic Breast Cancer; HER2-negative Breast Cancer

Keywords

breast cancer; advanced, metastatic; metastatic; progression; HR+; HER2-; capivasertib; eHealth; ePRO

Outcome Measures

Primary Outcomes (2)

• Superiority* of TTNT1 in patients receiving capivasertib compared to an evidence-based "standard TTNT1 curve" for patients without capivasertib.

  * Statistical comparison by survival modelling of time on treatment including competing risks. * Standard curve is derived from placebo + fulvestrant arm of CAPItello-291 trial and corresponds to 17% remaining "on-treatment" at 12 months. * Stratification by eHealth support vs. no eHealth support

  Last-patient-in plus 12 months

• Superiority* of PRO-adherence compared to non-adherence regarding TTDQoL (aka DQoL-free interval).

  * The event DQoL is defined in terms of a 10-point drop of the FACT-G score compared to baseline. * A patient is classified here as "PRO-non-adherent" if she does not use CANKADO on 60 or more of the first 90 days, otherwise as "PRO-adherent".

  through study completion, after 170 total DQoL-events occurred

Secondary Outcomes (4)

• Progression-free survival (PFS): defined by either: • evidence of disease progression as assessed by treating physician or • death

  From date of inclusion until the date of first documented progression, assessed up to 60 months

• Overall survival (OS)

  From date of inclusion until the date of first documented progression, assessed up to 60 months

• Superiority of eHealth support (and summary statistics) regarding TTDQoL compared to patients entering the trial without eHealth support.**

  From date of inclusion until the date of first documented progression, assessed up to 60 months

• Evaluation of prophylactic and reactive treatments for AESI management

  Treatment start until end of study, assessed up to 60 months

Other Outcomes (2)

• Adverse Events with Common Terminology Criteria for Adverse Events (CTCAE) version 5 grade 3 and 4

  Treatment start until end of study, assessed up to 60 months

• Adverse Events of Specila Interest (AESI)-rate

  Treatment start until end of study, assessed up to 60 months

Study Arms (1)

Capivasertib

EXPERIMENTAL

2x400 mg, peroral, for 4 days, followed by 3 days off treatment

Drug: Capivasertib

Interventions

Capivasertib DRUG

2x400 mg, peroral, for 4 days, followed by 3 days off treatment

Capivasertib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Females (≥18 years, pre-, peri- or post-menopausal) and males (≥18 years) at the time of signing the informed consent form
• a. 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 GNRH agonist. Patients are to have commenced concomitant treatment with GNRH agonist prior to or on Cycle 1, Day 1 and must be willing to continue it for the duration of the study.
• b. Post-menopausal women are defined as: i. aged ≥60 years of age, OR ii. 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 iii. documented bilateral oophorectomy.
• Histologically confirmed HR+/HER2- breast cancer determined from the most recent tumour sample (primary or metastatic) as per WHO classification. To fulfil the requirement of HR+ disease, a breast cancer must express ER with or without co-expression of progesterone receptor.
• Therefore, tumours must be:
• a. 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, b. 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, and c. 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 radiological or objective evidence of recurrence or progression (the cancer should have shown progression during or after most recent therapy); 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 ET (endocrine-based therapy) containing regimen (single agent or in combination) and have:
• a. Radiological evidence of breast cancer recurrence or progression while on, or within 12 months of the end of (neo)adjuvant treatment with an ET, 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).
• Presence of one or more of the PIK3CA/AKT1/PTEN biomarkers, preferably determined in tumour tissue\*
• Decision to newly initiate capivasertib
• Informed consent provided by patient prior to participation in the trial and before initiation of any study-specific measures
• having received a bilateral tubal ligation/occlusion (combined with a barrier method),
• or using a highly effective method of contraception for the duration of the study (from the time they sign consent) and for 3 months after the last dose of capivasertib / GNRH and for 2 years after the last dose of fulvestrant to prevent pregnancy.
• Total/true abstinence When the patient refrains from any form of sexual intercourse and this is in line with their usual and/or preferred lifestyle; this must continue for the duration of the study and for 3 months after the last dose of capivasertib/ GNRH and for 2 years after the last dose of fulvestrant to prevent pregnancy.

You may not qualify if:

• Absence of an alteration in the PIK3CA/AKT1/PTEN biomarkers
• Previous enrolment in the present study
• Participation in another clinical study with any investigational medicinal product and still on IMP treatment or have participated in an interventional study that remains blinded
• A disease burden that makes the patient ineligible for endocrine-based therapy per the investigator's best judgement (e.g., symptomatic visceral disease that is potentially life threatening in the short-term)
• Known history of drug or alcohol abuse within 1 year of screening
• Except for alopecia, any unresolved toxicities from prior therapy CTCAE Grade ≥2 at the time of starting study treatment
• Leptomeningeal metastases
• Spinal cord compression or brain metastases unless asymptomatic, treated and stable, and not requiring steroids within 4 weeks prior to study treatment initiation
• Clinically significant abnormalities of glucose metabolism as defined by any of the following:
• a. HbA1c ≥8.0% (63.9 mmol/mol) at screening. Note: for any patient with evidence of impaired glucose control or insulin resistance refer to the Capivasertib Toxicity Management Guidelines.
• Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:
• Absolute neutrophil count \<1.5 × 109/L
• Platelet count \<100 × 109/L
• Haemoglobin \<9 g/dL (\<5.59 mmol/L). \[NOTE: any blood transfusion must be \>14 days prior to the determination of a haemoglobin ≥9 g/dL (≥5.59 mmol/L)\]
• Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) \>2.5 times upper limit of normal (ULN) if no demonstrable liver metastases or \>5 × ULN in the presence of liver metastases

Sponsors & Collaborators

• West German Study Group: lead
• AstraZeneca: collaborator

Study Sites (7)

Institut Jules Bordet

Anderlecht, 1070, Belgium

NOT YET RECRUITING

CHC MontLegia

Liège, 4000, Belgium

NOT YET RECRUITING

St. Elisabeth-Krankenhaus GmbH, Brustzentrum - Senologie

Cologne, North Rhine-Westphalia, 50935, Germany

NOT YET RECRUITING

Universitätsklinikum Essen

Essen, North Rhine-Westphalia, 45130, Germany

NOT YET RECRUITING

Brustzentrum Niederrhein, Johanniter Bethesda Krankenhaus

Mönchengladbach, North Rhine-Westphalia, 41061, Germany

RECRUITING

Universitätsklinikum Münster AöR Brustzentrum

Münster, North Rhine-Westphalia, 48149, Germany

NOT YET RECRUITING

Champalimaud Clinical Centre

Lisbon, 1400-038, Portugal

NOT YET RECRUITING

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis; Disease Progression

Interventions

capivasertib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes

Study Officials

• Peter Schmid, PHD Dr

  Westdeutsche Studiengruppe GmbH

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rico Laage, Dr.

CONTACT

02161566230; rico.laage@wsg-online.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a multicentre, interventional, prospective, one-armed, open-label, phase-III-trial to evaluate the use of capivasertib in patients with HR+/HER2- advanced breast cancer and progression on prior endocrine-based treatment The study will consist of: A. a recruitment phase, 24 months, during which the patients are screened and enrolled B. a study treatment and follow-up phase of up to 60 months until end of study, dependent on timepoint of enrolment in the study.

Study Record Dates

• First Submitted: November 19, 2025
• First Posted: December 15, 2025
• Study Start: November 27, 2025
• Primary Completion (Estimated): March 1, 2030
• Study Completion (Estimated): March 1, 2030
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

BE (2); PT (1); DE (4)