Gedatolisib Plus Fulvestrant With or Without Palbociclib vs Standard-of-Care for the Treatment of Patients With Advanced or Metastatic HR+/HER2- Breast Cancer (VIKTORIA-1)

Trial number:
NCT05501886
Trial phase:
3
Study type:
Targeted therapy, Chemotherapy
Overall status:
Not yet recruiting

Study start date

September, 2022

Scientific title

Phase 3, Open-Label, Randomized, Study Comparing Gedatolisib Combined With Fulvestrant & With or Without Palbociclib to Standard-of-Care Therapies in Patients With HR-Positive, HER2-Negative Advanced Breast Cancer Previously Treated With a CDK4/6 Inhibitor in Combination w/Non-Steroidal Aromatase Inhibitor Therapy

Summary

This is a Phase 3, open-label, randomized, clinical trial evaluating the efficacy and safety of gedatolisib plus fulvestrant with or without palbociclib for the treatment of patients with locally advanced or metastatic HR+/HER2- breast cancer following progression on or after CDK4/6 and aromatase inhibitor therapy.

Histologically or cytologically confirmed diagnosis of metastatic or locally advanced breast cancer 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.Negative pregnancy test for women of childbearing potential. Female subjects of childbearing potential must use an effective and/or acceptable contraceptive method from screening until 1 year after the last dose of study treatment Confirmed diagnosis of estrogen receptor positive and/or progesterone receptor positive, as per American Society of Clinical Oncology/College of American Pathologists (ASCO-CAP) guidelines (2020), based on most recent tumor biopsy utilizing an assay consistent with local standards Documented HER2 immunohistochemistry (IHC) negative as per ASCO-CAP 2018 guidance Adequate archival or fresh tumor tissue for the analysis of PIK3CA mutational status Subject must have documentation of radiological disease progression on or after the last prior treatment and also have radiologically evaluable disease (measurable and/or non-measurable) according to RECIST v1.1, per local assessment. Subjects with bone only disease must have lytic or mixed lytic/blastic lesions that can be accurately assessed; bone only blastic lesions with no soft tissue component is not allowed. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 Life expectancy of at least 3 months Progressed during or after CDK4/6 inhibitor combination treatment with non-steroidal aromatase inhibitor (AI) Adequate bone marrow, hepatic, renal and coagulation function

History of malignancies other than adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for ≥3 yearsPrior treatment with a phosphoinositide 3-kinase (PI3K) inhibitor, a protein kinase B (Akt) inhibitor, or a mechanistic target of rapamycin (mTOR) inhibitor Prior treatment with chemotherapy and antibody drug conjugates for advanced disease is not permitted (prior adjuvant or neoadjuvant chemotherapy is permitted) More than 2 lines of prior endocrine therapy treatment Bone only disease that is only blastic with no soft tissue component Subjects with type 1 diabetes or uncontrolled type 2 diabetes

Known and untreated, or active, brain or leptomeningeal metastases

a. Subjects with previously treated central nervous system (CNS) metastases may be enrolled in the study if they meet the following criteria: do not require supportive therapy with steroids; do not have seizures and do not exhibit uncontrolled neurological symptoms; stable disease confirmed by radiographic assessment within at least 4 weeks prior to enrollment

Patients with advanced, symptomatic, visceral spread that are at risk of life-threatening complication in the short-term

History of clinically significant cardiovascular abnormalities such as: Congestive heart failure (New York Heart Association (NYHA) classification ≥ II within 6 months of study entry

Myocardial infarction within 12 months of study entryHistory of any uncontrolled (or untreated) clinically significant cardiac arrhythmias, (e.g., ventricular tachycardia), complete left bundle branch block, high grade AV block (e.g., bifascicular block, Mobitz type II and third degree AV block), supraventricular, nodal arrhythmias, or conduction abnormality in the previous 12 months Uncontrolled hypertension defined by systolic blood pressure (SBP) ≥160 mmHg and/or diastolic blood pressure (DBP) ≥100 mmHg, with or without antihypertensive medication (initiation or adjustment of antihypertensive medication[s] is allowed prior to screening)

Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:

i. Risk factors for Torsades de Pointes (TdP) including uncorrected hypokalemia or hypomagnesemia, or history of clinically significant/symptomatic bradycardiaii. On screening, inability to determine the corrected QT interval using Fridericia's formula (QTcF) on the ECG (i.e., unreadable or not interpretable) or QTcF >480 msec (determined by mean of triplicate ECGs at screening) Known hypersensitivity to the study drugs or their components Pregnant or breast-feeding women

Concurrent participation in another interventional clinical trial

Subjects must agree not to participate in another clinical trial (other than observational) at any time during participation in VIKTORIA-1.

Study design

Primary purpose: Treatment, Allocation: Randomized, Intervention model: Parallel Assignment, Masking: None (Open Label),

Conditions

Breast Cancer

Other study ID numbers

CELC-G-301; 2021-005235-24

Choose trial site (211)

Farrer Park
Farrer Park Not yet recruiting