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Phase 3 Clinical Trial of Gedatolisib in Patients with HR Positive, HER2 Negative Advanced or Metastatic Breast Cancer (VIKTORIA-1)
EU CTIS ID: 2022-502145-10-00
What this study is testing
Study 1: To compare the efficacy, as measured by progression-free survival (PFS), of gedatolisib in combination with palbociclib and fulvestrant (Arm A) to fulvestrant (Arm C) in adults with HR+/HER2-/PIK3CA wild type (WT) advanced breast cancer whose disease has progressed on prior CDK4/6 therapy in combination with non-steroidal aromatase inhibitor (AI) therapy. To compare efficacy, as measured by PFS, of gedatolisib in combination with fulvestrant (Arm B) to Arm C in adults with HR+/HER2-/PIK3CA WT advanced breast cancer whose disease has progressed on prior CDK4/6 therapy in combination with non-steroidal AI therapy. Study 2: To compare the efficacy, as measured by PFS, of gedatolisib in combination with palbociclib and fulvestrant (Arm D) to alpelisib with fulvestrant (Arm E) in adults with HR+/HER2-/PIK3CA mutated (MT) advanced breast cancer whose disease has progressed on prior CDK4/6 therapy in combination with non-steroidal AI therapy
- Therapeutic confirmatory (Phase III)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- Adults ≥18 years of age and meet one of the following criteria: a. Women who are postmenopausal, defined as one of the following: i. Women 18–59 years of age (at the time of consent) with cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause, and serum estradiol and follicle-stimulating hormone (FSH) level within the laboratory’s reference range for postmenopausal females ii. Women ≥60 years of age (at the time of consent) with cessation of menses for at least 12 consecutive months iii. Documented bilateral oophorectomy iv. Medically confirmed ovarian failure b. Pre/perimenopausal women with medically-induced menopause by treatment with the luteinizing hormone-releasing hormone (LHRH) agonist goserelin, the gonadotropin releasing hormone (GnRH) agonist leuprolide (Lupron Depot), or equivalent agents to induce chemical menopause c. Male subjects must use an effective and/or acceptable contraceptive method from screening until 1 year after the last dose of study treatment
- Progressed during or after CDK4/6 inhibitor combination treatment with non-steroidal aromatase inhibitor (AI)
- Resolution of all toxicities related to prior therapies or surgical procedures to NCI CTCAE v.5.0 Grade ≤1 (except alopecia)
- Left ventricular ejection fraction ≥50% at baseline
- At least 2 weeks beyond treatment with a targeted therapy, hormonal therapy, or major surgery and at least 3 weeks beyond immunotherapy and/or radiation therapy and recovered from all acute toxicities prior to randomization (adverse events [AEs] from prior anticancer agents recovered to Grade ≤1 or lower; except alopecia)
- Adequate bone marrow, hepatic, renal and coagulation function as defined by the following: a. Absolute neutrophil count ≥1.5 × 109/L (maintained without growth factor support within 7 days of C1D1) b. Hemoglobin ≥9.0 g/dL (90 g/L) (maintained without transfusion support within 7 days of C1D1) c. Platelets ≥100 × 109/L e. Potassium within normal limits, or corrected with supplements f. Calcium (corrected for serum albumin) and magnesium within normal limits or Grade ≤1 if judged clinically not significant by the Investigator g. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × upper limit of normal (ULN) (if no hepatic metastases); if hepatic tumor involvement, AST and ALT ≤5 × ULN h. Total bilirubin ≤1.5 × ULN (total bilirubin≤3.0 × ULN and direct bilirubin ≤1.5 × ULN in patients with Gilbert’s Syndrome) i. Serum amylase ≤1.5 × ULN (subjects with values >1.5 × ULN may be allowed if there are no clinical and radiological signs of pancreatitis) j. Serum lipase ≤1.5 × ULN (subjects with values >1.5 × ULN may be allowed if there are no clinical and radiological signs of pancreatitis) k. Prothrombin time (PT)/International Normalized Ratio (INR) ≤1.5 × ULN if not on anticoagulants l. Calculated creatinine clearance (CrCL) >50 mL/min using the Cockcroft and Gault equation i. Subjects with CrCL 40-50 mL/min who, in the opinion of the Investigator, are able to safely undertake study therapy may be eligible after discussion with Sponsor’s medical monitor
You likely can't join if
- 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 years
- History of drug induced pneumonitis or interstitial lung disease
- Subjects that, in the opinion of the Investigator, are unable to undertake study therapy or comply with study requirements a. Current uncontrolled medical, psychological, or social conditions that may interfere with the patient’s participation in the study or evaluation of the study results b. Where applicable per country regulation, the subject must not currently be committed to an institution by virtue of an order issued either by judicial or administrative authorities
- Prior treatment with a phosphoinositide 3 kinase (PI3K) inhibitor, a protein kinase B (Akt) inhibitor, or a mechanistic target of rapamycin (mTOR) inhibitor
- Pregnant or breast-feeding women
- Concurrent participation in another interventional clinical trial a. Subjects must agree not to participate in another clinical trial (other than observational trials) during participation in VIKTORIA-1 and until discontinuation of study treatment
See the full eligibility criteria
Who can join
- Adults ≥18 years of age and meet one of the following criteria: a. Women who are postmenopausal, defined as one of the following: i. Women 18–59 years of age (at the time of consent) with cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause, and serum estradiol and follicle-stimulating hormone (FSH) level within the laboratory’s reference range for postmenopausal females ii. Women ≥60 years of age (at the time of consent) with cessation of menses for at least 12 consecutive months iii. Documented bilateral oophorectomy iv. Medically confirmed ovarian failure b. Pre/perimenopausal women with medically-induced menopause by treatment with the luteinizing hormone-releasing hormone (LHRH) agonist goserelin, the gonadotropin releasing hormone (GnRH) agonist leuprolide (Lupron Depot), or equivalent agents to induce chemical menopause c. Male subjects must use an effective and/or acceptable contraceptive method from screening until 1 year after the last dose of study treatment
- Progressed during or after CDK4/6 inhibitor combination treatment with non-steroidal aromatase inhibitor (AI)
- Resolution of all toxicities related to prior therapies or surgical procedures to NCI CTCAE v.5.0 Grade ≤1 (except alopecia)
- Left ventricular ejection fraction ≥50% at baseline
- At least 2 weeks beyond treatment with a targeted therapy, hormonal therapy, or major surgery and at least 3 weeks beyond immunotherapy and/or radiation therapy and recovered from all acute toxicities prior to randomization (adverse events [AEs] from prior anticancer agents recovered to Grade ≤1 or lower; except alopecia)
- Adequate bone marrow, hepatic, renal and coagulation function as defined by the following: a. Absolute neutrophil count ≥1.5 × 109/L (maintained without growth factor support within 7 days of C1D1) b. Hemoglobin ≥9.0 g/dL (90 g/L) (maintained without transfusion support within 7 days of C1D1) c. Platelets ≥100 × 109/L e. Potassium within normal limits, or corrected with supplements f. Calcium (corrected for serum albumin) and magnesium within normal limits or Grade ≤1 if judged clinically not significant by the Investigator g. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × upper limit of normal (ULN) (if no hepatic metastases); if hepatic tumor involvement, AST and ALT ≤5 × ULN h. Total bilirubin ≤1.5 × ULN (total bilirubin≤3.0 × ULN and direct bilirubin ≤1.5 × ULN in patients with Gilbert’s Syndrome) i. Serum amylase ≤1.5 × ULN (subjects with values >1.5 × ULN may be allowed if there are no clinical and radiological signs of pancreatitis) j. Serum lipase ≤1.5 × ULN (subjects with values >1.5 × ULN may be allowed if there are no clinical and radiological signs of pancreatitis) k. Prothrombin time (PT)/International Normalized Ratio (INR) ≤1.5 × ULN if not on anticoagulants l. Calculated creatinine clearance (CrCL) >50 mL/min using the Cockcroft and Gault equation i. Subjects with CrCL 40-50 mL/min who, in the opinion of the Investigator, are able to safely undertake study therapy may be eligible after discussion with Sponsor’s medical monitor
- Must be willing and able to comply with protocol-specified schedules of assessments, treatment plans, laboratory tests, and other study procedures
- Ability to understand the investigational nature of the study and sign the informed consent
- 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 (2 years for fulvestrant) after the last dose of study treatment
- Histologically or cytologically confirmed diagnosis of metastatic or locally advanced breast cancer
- 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 (Wolff 2018); if result by IHC is +2 (equivocal), an in situ hybridization test must be performed.
- Adequate tumor tissue for the analysis of PIK3CA mutational status by Therascreen®PIK3CA RGQ PCR test and identified PIK3CA status (mutant or nonmutant) b. Patients with confirmed PIK3CA MT are eligible for treatment with alpelisib in combination with fulvestrant (per PIQRAY® USPI, SmPC) and will be assigned to Study 2 c. All other patients who do not have confirmed PIK3CA MT will be assigned to Study 1 (unless Study 1 enrollment has been completed)
- Subjects must have documentation of radiological disease progression on or after the last prior treatment and also have (measurable disease according to RECIST v1.1, per local assessment a. In case of bone only disease i. Subjects must have at least one lytic bone lesion or mixed lytic/blastic bone lesion with identifiable soft tissue components that can be evaluated for changes in size ii. Subjects with only blastic bone lesions with no soft tissue component are not eligible for enrollment b. If radiotherapy was used during ≤3 months prior to randomization, the lesions selected for response assessment must be outside of the field of prior radiotherapy or have documented progression following radiation therapy
- Eastern Cooperative Oncology Group (ECOG) performance status of 0–1
- Life expectancy of at least 3 months
What rules you out
- 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 years
- History of drug induced pneumonitis or interstitial lung disease
- Subjects that, in the opinion of the Investigator, are unable to undertake study therapy or comply with study requirements a. Current uncontrolled medical, psychological, or social conditions that may interfere with the patient’s participation in the study or evaluation of the study results b. Where applicable per country regulation, the subject must not currently be committed to an institution by virtue of an order issued either by judicial or administrative authorities
- Prior treatment with a phosphoinositide 3 kinase (PI3K) inhibitor, a protein kinase B (Akt) inhibitor, or a mechanistic target of rapamycin (mTOR) inhibitor
- Pregnant or breast-feeding women
- Concurrent participation in another interventional clinical trial a. Subjects must agree not to participate in another clinical trial (other than observational trials) during participation in VIKTORIA-1 and until discontinuation of study treatment
- Prior treatment with chemotherapy and antibody drug conjugates (e.g., Enhertu®) for advanced disease is not permitted (prior adjuvant or neoadjuvant chemotherapy is permitted). Subjects whose disease progressed to metastatic or advanced within less than 6 months of completing adjuvant or neoadjuvant therapy will be considered as having received chemotherapy for advanced disease.
- More than 2 lines of prior endocrine therapy treatment for metastatic or locally advanced breast cancer
- Bone only disease that is only blastic with no soft tissue component
- Subjects with type 1 diabetes or uncontrolled type 2 diabetes
- Active human immunodeficiency virus (HIV) infection. a. Subjects with well controlled HIV infection may be allowed if CD4+ T-cell (CD4+) counts >350 cells/μL b. Subjects without a history of AIDS-defining opportunistic infections may be eligible for enrollment
- 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
- Known seropositive for or active viral infection with hepatitis B virus a. Hepatitis B surface antigen (HBsAg) positive b. HBsAg negative, hepatitis B surface antibody (anti-HBs) positive and/or hepatitis B core antibody (anti-HBc) positive and detectable viral DNA by PCR [Note: Subjects who are HBsAg negative and viral DNA PCR negative are eligible.]
- Known seropositive for, or active infection with hepatitis C virus a. Subjects with positive hepatitis C virus (HCV) antibodies are eligible with negative PCR test for HCV
- Medical history or concurrent conditions that are contraindicated for investigational treatments in this study (alpelisib) a. Active osteonecrosis of the jaw from previous or concurrent treatment with bisphosphonates/denosumab b. History of severe cutaneous reactions (e.g., Stevens-Johnson syndrome)
- 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: a. Congestive heart failure (New York Heart Association (NYHA) classification ≥ II [NYHA 1994]) within 6 months of study entry b. Myocardial infarction within 12 months of study entry c. History 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 d. 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) e. 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 bradycardia ii. 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)
- Gastrointestinal tract disease resulting in an inability to absorb oral medication
- History of acute pancreatitis within 12 months of screening or past medical history of chronic pancreatitis
- Unable to swallow oral medication tablets/capsules
- Known hypersensitivity to the study drugs or their components
- History of pulmonary embolus or deep vein thrombosis diagnosed and/or treated within the previous 6 months
The study team makes the final eligibility decision.
Where it's taking place
- Canada
- Korea, Republic of
- India
- Brazil
- United States
- Mexico
- Argentina
- Singapore
- United Kingdom
- Taiwan
- Australia
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18-64 years, 65+ years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Canada; Korea, Republic of; India; Brazil; United States; Mexico and 5 more location(s). Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.