Effect of Capivasertib on ctDNA in ER Positive Breast Cancer

NCT06613516 | Withdrawn Phase 2 DMC

• 2 other identifiers: 22CX75302022-000802-82
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

There is growing evidence that cancer DNA (called circulating tumour DNA - ctDNA) in the blood is often an early sign that the cancer is likely to return. The aim of this study is to investigate whether treating women who have detectable ctDNA in their blood with a drug called Capivasertib can help control ctDNA levels and prevent developing metastatic or secondary breast cancer. A recruitment of 20 women with oestrogen receptor (ER) positive breast cancer (who are already on standard of care hormone therapy who are being treated with curative intent) is aimed for; which means that the disease has not yet spread to distant parts of the body. Each subject will be dosed with 400mg of Capivasertib twice a day for a maximum period of two years.

Conditions

Breast Cancer; Oestrogen Receptor Positive Breast Cancer

Keywords

Breast Cancer; Oestrogen receptor positive breast cancer

Outcome Measures

Primary Outcomes (3)

• Percentage of patients with complete ctDNA clearance

  To monitor ctDNA dynamics during treatment with Capivasertib based on the percentage of patients with ctDNA clearance compared to baseline

  2 years

• Duration of ctDNA clearance

  To monitor ctDNA dynamics during treatment with Capivasertib based on measuring the duration of ctDNA clearance

  2 years

• 50% ctDNA clearance

  To monitor ctDNA dynamics during treatment with Capivasertib based on the percentage of patients with over 50% decrease in ctDNA levels compared to baseline

  2 years

Study Arms (1)

Subject to be dose with Capivasertib bidaily

EXPERIMENTAL

400mg of Capivasertib to be dosed to patients and taken twice a day for a maximum of two years

Drug: Capivasertib

Interventions

Capivasertib DRUG

Capivasertib is a selective inhibitor of the kinase activity of the serine/threonine Akt/PKB pathway that may potentially provide clinical benefit over a range of therapeutic indications. Capivasertib comes in capsule form in two forms; 160mg or 200mg

Subject to be dose with Capivasertib bidaily

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Study is limited to biological females as this study is investigating breast cancer therapeutics
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent prior to any study specific procedures
• Female aged \>18 years
• Histologically confirmed ER positive HER2 negative breast cancer
• Post menopausal (or biochemically post-menopausal)
• Completed standard initial treatment and established on aromatase inhibitor (AI) for \> 6 months and planned for at least 2 more years
• Tolerating AI well
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (see Appendix 1) with no deterioration over the previous 2 weeks prior to baseline or day of first dosing
• Minimum life expectancy of 12 weeks
• Availability of tissue from diagnosis/treatment to assess ctDNA status
• Relatively high risk for relapse (all except T1N0 or T2N0) using a risk stratified recruitment process
• Adequate organ and bone marrow function as follows (a-c cannot be met with transfusions or growth factor support administered within 14 days of starting the first dose):
• Haemoglobin ≥9.0 g/dL (\>5.59 mmol/L).
• Absolute neutrophil count ≥1.0×109/L.
• Platelet count ≥100×109/L.
• Total bilirubin ≤1.5×the upper limit of normal (ULN) or ≤3×ULN in the presence of documented Gilbert's syndrome (unconjugated hyperbilirubinemia).

You may not qualify if:

• Metastatic disease at screening
• ECOG performance status \>1 (see Appendix 1)
• History of another primary malignancy except for malignancy treated with curative intent with no known active disease ≥ 5 years before the first dose of study intervention and of low potential risk for recurrence. Exceptions include basal cell carcinoma of the skin and squamous cell carcinoma of the skin that has undergone potentially curative therapy
• Known history of drug or alcohol abuse within 2 years
• History of interstitial lung disease
• Any other disease, 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
• Clinically significant abnormalities of glucose metabolism as defined by any of the following at screening:
• Patients with diabetes mellitus type I or diabetes mellitus type II requiring insulin treatment
• HbA1c ≥ 8.0% (63.9 mmol/mol)
• Prior treatment with any of the following:
• Participation in another clinical study with an IMP administered in the last \<\<2 weeks or 5 half-lives, whichever is longer
• AKT, PI3K and MTOR inhibitors
• Any other chemotherapy, immunotherapy, immunosuppressant medication (other than corticosteroids) or anticancer agents (other than current endocrine therapy with AI +/- LHRH analogies) within 3 weeks of the first dose of study treatment. A longer washout may be required for drugs with a long half-life (eg biologics) as agreed with the sponsor
• Palliative radiotherapy within 2 weeks; or radiotherapy to more than 30% of the bone marrow within 4 weeks before the first dose of study intervention
• Major surgical procedure (excluding placement of vascular access) or significant traumatic injury within 4 weeks of the first dose of study intervention or an anticipated need for major surgery during the study

Sponsors & Collaborators

• Imperial College London: lead
• AstraZeneca: collaborator
• Sharp: collaborator
• Natera, Inc.: collaborator

Study Sites (1)

Imperial College Healthcare Trust

London, United Kingdom

Location

Related Publications (4)

• Garcia-Murillas I, Schiavon G, Weigelt B, Ng C, Hrebien S, Cutts RJ, Cheang M, Osin P, Nerurkar A, Kozarewa I, Garrido JA, Dowsett M, Reis-Filho JS, Smith IE, Turner NC. Mutation tracking in circulating tumor DNA predicts relapse in early breast cancer. Sci Transl Med. 2015 Aug 26;7(302):302ra133. doi: 10.1126/scitranslmed.aab0021.

  PMID: 26311728 BACKGROUND

• Jones RH, Casbard A, Carucci M, Cox C, Butler R, Alchami F, Madden TA, Bale C, Bezecny P, Joffe J, Moon S, Twelves C, Venkitaraman R, Waters S, Foxley A, Howell SJ. Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic, oestrogen receptor-positive breast cancer (FAKTION): a multicentre, randomised, controlled, phase 2 trial. Lancet Oncol. 2020 Mar;21(3):345-357. doi: 10.1016/S1470-2045(19)30817-4. Epub 2020 Feb 5.

  PMID: 32035020 BACKGROUND

• Coombes RC, Page K, Salari R, Hastings RK, Armstrong A, Ahmed S, Ali S, Cleator S, Kenny L, Stebbing J, Rutherford M, Sethi H, Boydell A, Swenerton R, Fernandez-Garcia D, Gleason KLT, Goddard K, Guttery DS, Assaf ZJ, Wu HT, Natarajan P, Moore DA, Primrose L, Dashner S, Tin AS, Balcioglu M, Srinivasan R, Shchegrova SV, Olson A, Hafez D, Billings P, Aleshin A, Rehman F, Toghill BJ, Hills A, Louie MC, Lin CJ, Zimmermann BG, Shaw JA. Personalized Detection of Circulating Tumor DNA Antedates Breast Cancer Metastatic Recurrence. Clin Cancer Res. 2019 Jul 15;25(14):4255-4263. doi: 10.1158/1078-0432.CCR-18-3663. Epub 2019 Apr 16.

  PMID: 30992300 BACKGROUND

• Pan H, Gray R, Braybrooke J, Davies C, Taylor C, McGale P, Peto R, Pritchard KI, Bergh J, Dowsett M, Hayes DF; EBCTCG. 20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years. N Engl J Med. 2017 Nov 9;377(19):1836-1846. doi: 10.1056/NEJMoa1701830.

  PMID: 29117498 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms

Interventions

capivasertib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Dr Farah Rehman

  Imperial College Healthcare Trust

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2024
• First Posted: September 26, 2024
• Study Start: February 1, 2025
• Primary Completion: September 16, 2025
• Study Completion: September 16, 2025
• Last Updated: December 24, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)