Capivasertib+Fulvestrant asTreatment for Locally Advanced(Inoperable) or Metastatic HR+/HER2- Breast Cancer in Chinese Patients

NCT06635447 | Active Not Recruiting Phase 3

• 1 other identifier: D3612R00016
• Study Type: interventional
• Target: 258
• Locations: 1 country
• Sites: 75

Brief Summary

This is a multi-center, two-cohorts, phase IIIb study of Capivasertib+Fulvestrant in HR+/HER2-ABC who had disease recurrence/progression following 1-2L endocrine therapy. The Primary objective is to assess the efficacy of capi+ful by assessment of TFST (Time to first subsequent treatment) of PIK3CA/AKT1/PTEN-altered subgroup in cohort1.

Conditions

Breast Cancer

Keywords

Breast Cancer; HR+/HER2-ABC; disease recurrence/progression

Outcome Measures

Primary Outcomes (1)

• Time to first subsequent treatment (TFST) of PIK3CA/AKT1/PTEN-altered population in Cohort 1

  To assess the efficacy of capi+ful by assessment of TFST (Time to first subsequent treatment) of PIK3CA/AKT1/PTEN-altered subgroup in cohort1

  From the first dose of study intervention to the earlier of start date of the first subsequent therapy after discontinuation of study intervention, or death in PIK3CA/AKT1/PTEN-altered population in Cohort 1, up to approximately 2 years

Secondary Outcomes (5)

• Progression-free survival (PFS) in PIK3CA/AKT1/PTEN-altered population in Cohort 1 and 2

  From first dose until objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from study treatment or receives another anti-cancer therapy before progression, up to 2 years

• Time to first subsequent treatment (TFST) in PIK3CA/AKT1/PTEN-altered population in Cohort 2

  From the first dose of study intervention to the earlier of start date of the first subsequent therapy after discontinuation of study intervention, or death in PIK3CA/AKT1/PTEN-altered population in Cohort 2, up to approximately 2 years

• Number of participants with AEs/SAEs

  From time of signature of the ICF, throughout the treatment period and including the 30-day follow-upperiod after discontinuation of study drug, up to approximately 2 years

• Objective response rate (ORR) in PIK3CA/AKT1/PTEN-altered population in Cohort 1 and 2

  The percentage of PIK3CA/AKT1/PTEN-altered subjects with at least one investigator-assessed response of CR or PR and will be based on a subset of all PIK3CA/AKT1/PTEN-altered subjects with measurable disease at baseline per the site investigator.

• Number of participants with AEs/SAEs in PIK3CA/AKT1/PTEN-altered population

  From time of signature of the ICF, throughout the treatment period and including the 30-day follow-upperiod after discontinuation of study drug in PIK3CA/AKT1/PTEN-altered population, up to approximately 2 years

Study Arms (2)

Cohort 1

EXPERIMENTAL

Capivasertib+Fulvestrant

Drug: Capivasertib; Drug: Fulvestrant

Cohort 2

EXPERIMENTAL

Capivasertib+Fulvestrant

Drug: Capivasertib; Drug: Fulvestrant

Interventions

Capivasertib DRUG

400 mg, oral, twice daily; 4 days on and 3 days off

Also known as: AZD5363

Cohort 1; Cohort 2

Fulvestrant DRUG

Fulvestrant IV

Cohort 1; Cohort 2

Eligibility Criteria

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

You may qualify if:

• Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the clinical study protocol (CSP).
• Provision of signed and dated, written ICF prior to any mandatory study specific procedures, sampling, and analyses.
• Patients must be aged ≥18 years at the time of signing the ICF
• Adult females, pre- and/or post-menopausal, and adult males -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 LHRH agonist. Patients are to have commenced concomitant treatment with LHRH agonist prior to or on Cycle 1, Day 1 and must be willing to continue on it for the duration of the study -Post-menopausal women are defined as: a)aged ≥60 years of age, or b)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 c)documented bilateral oophorectomy
• Histologically confirmed HR+/HER2- breast cancer determined from the most recent tumour sample (primary or metastatic), as per the American Society of Clinical Oncology and College of American Pathologists guideline recommendations. To fulfil the requirement of HR+ disease, a breast cancer must express ER with or without co-expression of progesterone receptor. 1)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, 2)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, 3)or the investigator assesses the condition as HR+ status and 4)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 radiographic or objective evidence of recurrence or progression (cancer that has progressed during or after a recent treatment period).; 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 endocrine therapy containing regimen (single agent or in combination) and have: a)Radiological evidence of breast cancer recurrence or progression during treatment or within 12 months after the end of treatment with a neoadjuvant or adjuvant endocrine therapy, 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) (for patients with breast cancer recurrence or progression while on, or within 12 months of the end of (neo)adjuvant treatment with an ET will be limited to approximately 10%).
• Patients must have at least 1 measurable lesion.
• Patients must be eligible for fulvestrant therapy as per local investigator assessment.
• Consent to submit and provide a mandatory FFPE tumour sample for central testing.
• Patients must be able to swallow and retain oral medication.
• Eastern Cooperative Oncology Group (ECOG)/ World Health Organisation (WHO) performance status 0 or 1 and life expectancy of ≥12 weeks.
• Patients with PIK3CA/AKT1/PTEN alterations confirmed by central laboratory NGS testing. (Note: Applicable exclusively to patients enrolled under Protocol Version 2.0.)

You may not qualify if:

• A disease burden that makes the patient ineligible for endocrine therapy per the investigator's best judgement (e.g., symptomatic visceral disease that is potentially life-threatening in the short-term)
• 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. Exceptions include adequately resected non-melanoma skin cancer and curatively treated in situ disease. Radiotherapy within 2 weeks prior to the first dose of study intervention. Major surgery (excluding placement of vascular access) within 4 weeks prior to study treatment initiation
• With the exception of alopecia, any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the time of starting study treatment
• Spinal cord compression or brain metastases unless asymptomatic, treated and stable and not requiring steroids within 4 weeks prior to study treatment initiation
• Leptomeningeal metastase
• Active tuberculosis infection (clinical evaluation that may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice).
• Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease
• Any of the following cardiac criteria: a)Mean resting QT interval corrected by Fridericia's formula (QTcF) \>470 msec obtained from 3 consecutive ECGs b)History of QT prolongation associated with other medications that required discontinuation of that medication. - Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block) c)Medical history significant for arrhythmia (e.g., multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia), which is symptomatic or requires treatment (CTCAE Grade 3), symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Participants with atrial fibrillation controlled by medication or arrhythmias controlled by pacemakers may be permitted to enter the study based on the Investigator judgement with cardiologist consultation recommended. d)Any factors that increase the risk of corrected QT interval (QTc) prolongation or risk of arrhythmic events such as heart failure, clinically significant electrolyte abnormalities including hypokalaemia, hypomagnesaemia, and hypocalcaemia, potential for Torsades de pointes, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age or any concomitant medication known to prolong the QT interval e)Experience of any of the following procedures or conditions in the preceding 6 months: coronary artery bypass graft, angioplasty, myocardial infarction, unstable angina pectoris, f)Congestive heart failure New York Heart Association (NYHA) grade ≥2
• Clinically significant abnormalities of glucose metabolism defined as 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: a)Absolute neutrophil count \<1.5 × 109/L b)Platelet count \<100 × 109/L c)Haemoglobin \<9 g/dL (\<5.59 mmol/L). \[NOTE: any blood transfusion must be \>14 days prior to the determination of a haemoglobin ≥9 g/dL (≥5.59 mmol/L)\] d)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 e)Total bilirubin \>1.5 × ULN (Patients with confirmed Gilbert's syndrome may be included in the study) f)Creatinine \>1.5 × ULN concurrent with creatinine clearance \<50 mL/min (measured or calculated by Cockcroft and Gault formula (using actual body weight) without the need for chronic dialysis therapy.
• As judged by the investigator, any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, or active infection
• 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 as per Table 19 Drug Interactions that affect Capivasertib.
• Known abnormalities in coagulation such as bleeding diathesis, or treatment with anticoagulants precluding intramuscular injections of fulvestrant or LHRH 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

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (75)

Research Site

Baoding, 071000, China

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Beijing, 100021, China

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Beijing, 100071, China

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Beijing, 100730, China

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Beijing, CN-100730, China

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Bengbu, 233004, China

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Changchun, 130021, China

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Changsha, 410008, China

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Changsha, 410011, China

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Changsha, 410013, China

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Chengdu, 610072, China

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Dalian, 116001, China

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Dalian, China

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Deyang, 618000, China

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Dongguan, 523009, China

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Foshan, 528000, China

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Fuzhou, 350001, China

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Fuzhou, 350011, China

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Guangzhou, 510060, China

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Guangzhou, 510120, China

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Guiyang, 550044, China

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Hangzhou, 310003, China

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Hangzhou, 310009, China

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Hangzhou, 310016, China

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Hangzhou, 310022, China

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Harbin, 150081, China

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Hefei, 230022, China

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Hefei, 230031, China

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Huizhou, 516001, China

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Jinan, 250012, China

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Jinhua, China

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Jining, 272029, China

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Kashgar, 844099, China

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Kunming, 650118, China

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Linhai, 317000, China

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Meizhou, 514031, China

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Nanchang, 330009, China

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Nanchong, 637000, China

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Nanjing, 210029, China

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Ningbo, 315099, China

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Ningbo, 315100, China

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Qingdao, 266042, China

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Shanghai, 200025, China

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Shanghai, 200080, China

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Shanghai, 201114, China

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Shanghai, 201210, China

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Shantou, 515063, China

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Shenyang, 110004, China

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Shenyang, 110042, China

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Shenzhen, 518020, China

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Shenzhen, 518036, China

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Shijiazhuang, 050020, China

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Sichuan, 610041, China

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Suining Shi, 629000, China

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Suzhou, 215004, China

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Taiyuan, 030000, China

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Tangshan, 063001, China

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Tianjin, 300060, China

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Ürümqi, 830000, China

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Ürümqi, 830054, China

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Wanzhou, 404000, China

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Weifang, 261000, China

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Wenzhou, 325000, China

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Wuhan, 430022, China

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Wuhan, 430030, China

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Xi'an, 710000, China

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Xi'an, 710006, China

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Xi'an, 710061, China

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Xiamen, 361003, China

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Xuzhou, 221005, China

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Yinchuan, 750000, China

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Zhanjiang, 524004, China

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Zhengzhou, 450000, China

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Zhengzhou, 450008, China

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Zhengzhou, 450052, China

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MeSH Terms

Conditions

Breast Neoplasms; Disease Progression

Interventions

capivasertib; Fulvestrant

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Zefei Jiang, PhD

  Clinical Trial Ethics Committee of The Fifth Medical Center of the Chinese People's Liberation Army General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2024
• First Posted: October 10, 2024
• Study Start: September 26, 2024
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): January 10, 2027
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitment at made to the EFPIA Pharma Data Sharing Principles .For details of our timeline please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement(non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to a air access. For additional details. please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

CN (75)