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

Recruiting now · Phase 3

Conditions studied: Breast Cancer, HR-positive Breast Cancer, Advanced Breast Cancer, Metastatic Breast Cancer, HER2-negative Breast Cancer

In brief

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. To evaluate benefit of capivasertib regarding time to next treatment (TTNT1) - i.e., time "on treatment" with capivasertib. 2. To evaluate the benefits of patient reported outcome(PRO)-adherence regarding the deterioration of quality of life (DQoL)-free interval. There is no active comparison group but a historical control group consisting of data of patients treated within the CAPItello-291-study.. Participants will take capivasertib accompanied by standard of care endocrine treatment and are asked to document ther quality of life on standardised questionnaires. Optionally, patients can use eHealth support via their own smart phones.

Key facts

Study ID: NCT07281833
Run by: Women's Cancer Study Group GmbH
People needed: 250
Starts: 2025-11-27
Expected to finish: 2030-03-01
Last updated by the study team: 2026-08-05

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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
A. Female patients of childbearing potential at inclusion must have a negative pregnancy test (serum) and additionally, - surgically sterile, - carry an intrauterine device (combined with a barrier method),
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.
Vasectomised sexual partner (with participant assurance that partner received post-vasectomy confirmation of azoospermia) combined with a barrier method or sexual partner with bilateral orchiectomy
Hormonal contraception is not acceptable.
B. Male patients must either be
surgically sterile
or using an highly effective method of contraception for the duration of the study (from the time they sign consent) and for 4 months after the last dose of capivasertib/ GNRH and for 2 years after the last dose of fulvestrant to prevent pregnancy in a partner.
Sexually abstinent men (i.e., refraining from heterosexual intercourse during the entire study duration) must continue for 4 months after the last dose of capivasertib/ GNRH and for 2 years after the last dose of fulvestrant to prevent pregnancy in a partner.
Male patients who intend to be sexually active with a woman of childbearing potential, must use a condom plus spermicide upon entering the study and until 4 months after the last dose of capivasertib and for 2 years after the last dose of fulvestrant to prevent pregnancy in a partner.
Highly effective methods of contraception should be considered in female partners of men taking capivasertib plus fulvestrant who are of childbearing potential.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 with no deterioration over the previous 2 weeks and life expectancy of ≥12 weeks

You may not qualify if…

Patients eligible for inclusion in this study must not meet any of the following criteria:
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
Total bilirubin >1.5 × ULN (Patients with confirmed Gilbert's syndrome may be included in the study)
Creatinine >1.5 × ULN concurrent with creatinine clearance <50 mL/min (measured or calculated by Cockcroft and Gault equation); creatinine clearance is only required when creatinine is >1.5 × ULN
Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, or active infection including tuberculosis, hepatitis B, hepatitis C, and human immunodeficiency virus (HIV), including those who have confirmed COVID 19 and any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the investigator's opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, may affect the interpretation of the results, render the patient at high risk from treatment complications or interferes with obtaining informed consent. Screening for chronic conditions is not required.
Note: Known active hepatitis B or C infection, positive hepatitis C antibody, positive hepatitis B virus surface antigen. Participants positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA. Patients receiving antiretroviral therapies which are strong inhibitors or inducers of CYP3A4 will be excluded due to the potential for drug-drug interaction with capivasertib
Known abnormalities in coagulation such as bleeding diathesis, or treatment with anticoagulants precluding intramuscular injections of fulvestrant or subcutaneous injections of GNRH agonist (if applicable)
Refractory nausea and vomiting, malabsorption syndrome, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection, or other condition that would preclude adequate absorption of capivasertib
Previous allogenic bone marrow or solid organ transplant
History of another primary malignancy
Known immunodeficiency syndrome

Where it is running

Champalimaud Clinical Centre — Lisbon, Portugal (enrolling)
St. Elisabeth-Krankenhaus GmbH, Brustzentrum - Senologie — Cologne, North Rhine-Westphalia, Germany (enrolling)
Universitätsklinikum Essen — Essen, North Rhine-Westphalia, Germany (enrolling)
Brustzentrum Niederrhein, Johanniter Bethesda Krankenhaus — Mönchengladbach, North Rhine-Westphalia, Germany (enrolling)
Institut Jules Bordet — Anderlecht, Belgium (enrolling)
Kliniken der Stadt Köln gGmbH, Krankenhaus Holweide — Cologne, Germany (enrolling)
Evanglisches Kliniken Essen Mitte — Essen, Germany (enrolling)
AGAPLESION Markus Krankenhaus — Frankfurt, Germany (enrolling)
Mammazentrum Hamburg am Krankenhaus Jerusalem — Hamburg, Germany (enrolling)
Gynäkologische Gemeinschaftspraxis-Ärztehaus am Bahnhofsplatz — Hildesheim, Germany (enrolling)
Klinikum der Universität München — München, Germany (enrolling)
Rotkreuzkliniken München — München, Germany (enrolling)
MVZ Media Vita (St. Franziskus-Hospital Münster) — Münster, Germany (enrolling)
MKS St. Paulus GmBH Mariankrankenhaus — Schwerte, Germany (enrolling)
Universitätsklinikum Ulm — Ulm, Germany (enrolling)
Universitätsklinikum Münster AöR Brustzentrum — Münster, North Rhine-Westphalia, Germany

Full record on ClinicalTrials.gov

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