Capivasertib+Fulvestrant vs Placebo+Fulvestrant as Treatment for Locally Advanced (Inoperable) or Metastatic HR+/HER2- Breast Cancer (NCT04305496) — Germany Trial Details

Condition(s) studied

Locally Advanced (Inoperable) or Metastatic Breast Cancer

Investigational drug(s) / intervention(s)

Fulvestrant: Patients will be administered 500 mg (2 injections) on Day 1 of Weeks 1 and 3 of Cycle 1, and then on Day 1, Week 1 of each cycle thereafter

Capivasertib: 400 mg BD (2 tablets of 200 mg taken twice a day = total daily dose 800 mg) given on an intermittent weekly dosing schedule. Patients will be dosed on Days 1 to 4 in each week of a 28-day treatment cycle

Placebo: Placebo to match 400 mg BD (2 tablets of placebo to match 200 mg taken twice daily = placebo to match total daily dose of 800 mg) given on an intermittent weekly dosing schedule. Patients will be dosed on Days 1 to 4 in each week of a 28-day treatment cycle

Study summary

Phase III, double-blind, randomised study assessing the efficacy of capivasertib + fulvestrant vs placebo + fulvestrant for the treatment of patients with locally advanced (inoperable) or metastatic HR+/HER2- breast cancer following recurrence or progression on or after AI therapy.

Eligibility

Sex

ALL

Min age

18 Years

Max age

130 Years

Healthy volunteers

No

Inclusion Criteria: 1. Adult females, pre- and/or post-menopausal, and adult males. Pre-menopausal (and peri-menopausal) 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 2. 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. 3. 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) 4. ECOG/WHO PS: 0-1 5. Patients are to have received treatment with an AI (aromatase inhibitor) containing regimen (single agent or in combination) and have: 1. Radiological evidence of breast cancer recurrence or progression while on, or within 12 months of the end of (neo)adjuvant treatment with an AI, OR 2. Radiological evidence of progression while on prior AI administered as a treatment line for locally advanced or metastatic breast cancer (this does not need to be the most recent therapy) 6. Patients must have measurable disease according to RECIST 1.1 and/or at least 1 lytic or mixed (lytic + sclerotic) bone lesion that can be assessed by CT or MRI; patients with sclerotic/osteoblastic bone lesions only in the absence of measurable disease are not eligible 7. FFPE tumour sample from primary/recurrent cancer for central testing Exclusion Criteria: 1. Symptomatic visceral disease or any disease burden that makes the patient ineligible for endocrine therapy per the investigator's best judgement 2. More than 2 lines of endocrine therapy for inoperable locally advanced or metastatic disease 3. 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 advanced breast cancer 4. Prior treatment with any of the following: 1. AKT, PI3K and mTOR inhibitors 2. Fulvestrant, and other SERDs 3. Any other chemotherapy, immunotherapy, immunosuppressant medication (other than corticosteroids) or anticancer agents within 3 weeks prior to study treatment initiation. 4. Potent inhibitors or inducers of CYP3A4 within 2 weeks prior to the first dose of study treatment (3 weeks for St John's wort) or drugs that are sensitive to CYP3A4 inhibition within 1 week prior to study treatment initiation. 5. Radiotherapy with a wide field of radiation up to 4 weeks before study treatment initiation (capivasertib/placebo) and/or radiotherapy with a limited field of radiation for palliation up to 2 weeks before study treatment initiation (capivasertib/placebo) 6. With the exception of alopecia, any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the time of starting study treatment 7. Spinal cord compression or brain metastases unless asymptomatic, treated and stable and not requiring steroids up to 4 weeks before study treatment initiation 8. Any of the following cardiac criteria: 1. Mean resting QT interval corrected by Fridericia's formula (QTcF) \>470 msec obtained from 3 consecutive ECGs 2. Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (eg, complete left bundle branch block, third degree heart block) 3. Any factors that increase the risk of corrected QT interval (QTc) prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, 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 4. Experience of any of the following procedures or conditions in the preceding 6 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, angina pectoris, congestive heart failure New York Heart Association (NYHA) grade ≥2 5. Uncontrolled hypotension - systolic blood pressure \<90 mmHg and/or diastolic blood pressure \<50 mmHg 6. Cardiac ejection fraction outside institutional range of normal or \<50% (whichever is higher) as measured by echocardiogram (or multiple-gated acquisition \[MUGA\] scan if an echocardiogram cannot be performed or is inconclusive) 9. Clinically significant abnormalities of glucose metabolism as defined by any of the following: 1. Patients with diabetes mellitus type 1 or diabetes mellitus type 2 requiring insulin treatment 2. HbA1c ≥8.0% (63.9 mmol/mol) 10. Known abnormalities in coagulation such as bleeding diathesis, or treatment with anticoagulants precluding intramuscular injections of fulvestrant or LHRH agonist (if applicable) 11. Currently pregnant (confirmed with positive pregnancy test) or breast-feeding

Primary outcome measure(s)

Progression Free Survival: Overall Population (Months) in the Global Cohort — Assessed every 8 weeks for the first 18 months and every 12 weeks thereafter, from randomization to radiological progression.
Progression free survival (PFS), defined as the time from randomization until progression per RECIST v1.1, as assessed by the investigator at the local site, or death due to any cause, in the global cohort. Participants who discontinue treatment prior to progression should continue to be scanned until progression. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) as at least a 20% increase in the sum of the longest diameter of target lesions (short axis diameter used for lymph nodes), or clinically significant increase in a non-target lesion, or the appearance of a new lesion(s).
Progression Free Survival: Overall Population (Percentage) in the Global Cohort — Assessed every 8 weeks for the first 18 months and every 12 weeks thereafter, from randomization to radiological progression.
Progression free survival (PFS), defined as the time from randomization until progression per RECIST v1.1, as assessed by the investigator at the local site, or death due to any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) as at least a 20% increase in the sum of the longest diameter of target lesions (short axis diameter used for lymph nodes), or clinically significant increase in a non-target lesion, or the appearance of a new lesion(s). Participants who discontinue treatment prior to progression should continue to be scanned until progression. Kaplan-Meier estimate was used.
Progression Free Survival: Altered Population (Months) in the Global Cohort — Assessed every 8 weeks for the first 2 years following objective disease progression or treatment discontinuation and then every 12 weeks.
Progression free survival (PFS), defined as the time from randomization until progression per RECIST v1.1, as assessed by the investigator at the local site, or death due to any cause.
Progression Free Survival: Altered Population (Percentage) in the Global Cohort — Assessed every 8 weeks for the first 2 years following objective disease progression or treatment discontinuation and then every 12 weeks.
Progression free survival (PFS), defined as the time from randomization until progression per RECIST v1.1, as assessed by the investigator at the local site, or death due to any cause. Kaplan-Meier estimate was used.
Progression Free Survival: Overall Population (Months) in the China Cohort — Assessed every 8 weeks for the first 18 months and every 12 weeks thereafter, from randomization to radiological progression.
Progression free survival (PFS), defined as the time from randomization until progression per RECIST v1.1, as assessed by the investigator at the local site, or death due to any cause, in the global cohort. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) as at least a 20% increase in the sum of the longest diameter of target lesions (short axis diameter used for lymph nodes), or clinically significant increase in a non-target lesion, or the appearance of a new lesion(s). Participants who discontinue treatment prior to progression should continue to be scanned until progression.
Progression Free Survival: Overall Population (Percentage) in the China Cohort — Assessed every 8 weeks for the first 18 months and every 12 weeks thereafter, from randomization to radiological progression.
Progression free survival (PFS), defined as the time from randomization until progression per RECIST v1.1, as assessed by the investigator at the local site, or death due to any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) as at least a 20% increase in the sum of the longest diameter of target lesions (short axis diameter used for lymph nodes), or clinically significant increase in a non-target lesion, or the appearance of a new lesion(s). Participants who discontinue treatment prior to progression should continue to be scanned until progression. Kaplan-Meier estimate was used.
Progression Free Survival: Altered Population (Months) in the China Cohort — Assessed every 8 weeks for the first 2 years following objective disease progression or treatment discontinuation and then every 12 weeks.
Progression free survival (PFS), defined as the time from randomization until progression per RECIST v1.1, as assessed by the investigator at the local site, or death due to any cause.
Progression Free Survival: Altered Population (Percentage) in the China Cohort — Assessed every 8 weeks for the first 2 years following objective disease progression or treatment discontinuation and then every 12 weeks.
Progression free survival (PFS), defined as the time from randomization until progression per RECIST v1.1, as assessed by the investigator at the local site, or death due to any cause Kaplan-Meier estimate was used.

Trial sites (215)

Facility	City	Region
Research Site	Gilbert	Arizona
Research Site	Orange	California
Research Site	San Francisco	California
Research Site	Whittier	California
Research Site	Fort Myers	Florida
Research Site	Jacksonville	Florida
Research Site	Westwood	Kansas
Research Site	Baltimore	Maryland
Research Site	Boston	Massachusetts
Research Site	Rochester	Minnesota
Research Site	Kansas City	Missouri
Research Site	St Louis	Missouri
Research Site	Paramus	New Jersey
Research Site	Farmington	New Mexico
Research Site	Lake Success	New York
Research Site	New York	New York
Research Site	Greensboro	North Carolina
Research Site	Chattanooga	Tennessee
Research Site	Nashville	Tennessee
Research Site	Dallas	Texas
Research Site	Midlothian	Virginia
Research Site	Puyallup	Washington
Research Site	Berazategui	Argentina
Research Site	Buenos Aires	Argentina
Research Site	La Rioja	Argentina
Research Site	Rosario	Argentina
Research Site	Viedma	Argentina
Research Site	Adelaide	Australia
Research Site	Ballarat	Australia
Research Site	Birtinya	Australia
Research Site	Box Hill	Australia
Research Site	Concord	Australia
Research Site	Kurralta Park	Australia
Research Site	North Sydney	Australia
Research Site	Orange	Australia
Research Site	Ringwood East	Australia
Research Site	South Brisbane	Australia
Research Site	Waratah	Australia
Research Site	Wendouree	Australia
Research Site	Brussels	Belgium

+ 175 more sites — see the full list on the official registry below.

More AstraZeneca trials in Germany

A Study to Evaluate Chemotherapy Plus Osimertinib Against Chemotherapy Plus Placebo in Patients With Non-small Cell Lung Cancer (NSCLC) Active, not recruiting

OverTTuRe: Characteristics, Treatment Patterns and Outcomes of Patients With ATTR Amyloidosis Recruiting

A Phase III Study of Ceralasertib Plus Durvalumab Versus Docetaxel in Patients With Non Small Cell Lung Cancer (NSCLC) Whose Disease Progressed On or After Prior Anti PD (L)1 Therapy And Platinum Based Chemotherapy Active, not recruiting

A Study of Dato-DXd Versus Investigator's Choice Chemotherapy in Patients With Locally Recurrent Inoperable or Metastatic Triple-negative Breast Cancer, Who Are Not Candidates for PD-1/PD-L1 Inhibitor Therapy (TROPION-Breast02) Active, not recruiting

A Study to Evaluate Safety, PK, PD and Efficacy of AZD5492, a T Cell-engaging Antibody Targeting CD20 in Subjects With R/R B-Cell Malignancies. Recruiting

Other trials for the same condition

Capivasertib + CDK4/6i + Fulvestrant for Advanced/Metastatic HR+/HER2- Breast Cancer (CAPItello-292) Active, not recruiting