Phase 3 Study of Gedatolisib as First-Line Treatment for Patients With HR-Positive, HER2-Negative Advanced Breast Cancer (VIKTORIA-2)
This is a Phase 3, open-label, randomized, clinical trial evaluating the efficacy and safety of gedatolisib plus fulvestrant and CDK4/6 Inhibitors for the treatment of patients with locally advanced or metastatic HR+/HER2- advanced breast cancer.
Study details:
This is a Phase 3, open-label, randomized clinical trial evaluating the efficacy and safety of gedatolisib plus endocrine therapy and palbociclib versus endocrine therapy and ribociclib for the treatment of patients with advanced (inoperable) or metastatic hormone receptor positive, human epidermal growth factor receptor 2 negative (HR+/HER2-) breast cancer. Following completion of the screening procedures to determine eligibility, patients will be assigned manually according to their endocrine sensitivity status to either Study 1 (endocrine-resistant) or Study 2 (endocrine-sensitive) and subsequently be randomized 1:1 to either investigational treatment or standard-of-care control. Study 1 is expected to enroll approximately 440 subjects with treatment-naïve endocrine-resistant ABC whose cancer progressed while receiving or within 12 months of completing adjuvant endocrine therapy.
The trial will evaluate the efficacy and safety of the investigational arm (gedatolisib combined with palbociclib and fulvestrant - Arm A) compared to the control arm (ribociclib combined with fulvestrant - Arm B). Study 2 is expected to enroll approximately 740 subjects with treatment-naïve endocrine-sensitive ABC whose cancer relapsed or progressed 12 months or more after completion of adjuvant endocrine therapy, or those with de novo metastatic disease without prior endocrine therapy exposure. The trial will evaluate the efficacy and safety of the investigational arm (gedatolisib combined with palbociclib and letrozole - Arm C) compared to the control arm (ribociclib combined with letrozole - Arm D).
Gedatolisib is an intravenously administered pan-PI3K/mTOR inhibitor. Palbociclib and ribociclib are CDK4/6 inhibitors. Fulvestrant is a selective estrogen receptor degrader (SERD).
Letrozole is an aromatase inhibitor (AI).
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
- Histologically or cytologically confirmed diagnosis of metastatic or locally advanced HR+/HER2- 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 for the duration of the study.
- Negative pregnancy test for females of childbearing potential. Female subjects who are not surgically sterile must use a medically effective contraceptive method from screening until 2 years after the last dose of study treatment.
- Progression of disease during or within 12 months of completing (neo)adjuvant ET.
- Adequate archival, fresh tumor tissue, or liquid biopsy for the analysis of PIK3CA mutational status.
- Permitted prior therapies: (neo)adjuvant fulvestrant or any selective ER degrader only if the treatment duration < 6 months; (neo)adjuvant chemotherapy; (neo)adjuvant CDK4/6 inhibitor, unless PD was on or within 6 months of discontinuation of CDK4/6i
- Subject has radiologically measurable disease according to RECIST v1.1, per local assessment. Patients with evaluable bone-only disease are not eligible. Patients with bone-only disease that has lytic or mixed lytic/blastic lesions and at least one measurable soft tissue component per RECIST v1.1 may be eligible.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
- Life expectancy of at least >6 months.
- Adequate bone marrow, hepatic, renal and coagulation function.
Exclusion criteria
- Concurrent malignancies other than adequately treated non-melanoma skin cancer. Previous malignancies in remission but curatively treated with no evidence of disease progression and judged by local Investigator to be at low risk of impacting health or survival while on study.
- Prior 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 systemic anticancer therapy for ABC
- Subjects with type 1 diabetes
- Known and untreated, or active, brain or leptomeningeal metastases
- History of clinically significant cardiovascular abnormalities
- History of drug-induced symptomatic interstitial lung disease (pneumonitis) or hepatitis
Eligibility
Age eligible for study : NA
Healthy volunteers accepted : No
Gender eligible for study: ALL
Things to know
Study dates
Study start:
Primary completion:
Study completion finish:
Study type
TREATMENT
Phase
- PHASE3
Study ID
NCT06757634
Intervention or treatment
DRUG: Arm A: Gedatolisib + Palbociclib or Ribociclib + Fulvestrant
DRUG: Arm B: Palbociclib or Ribociclib + Fulvestrant
Conditions
- Breast Cancer
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Research sites nearby
Closest Location:
GenesisCare - St Andrews
Select from list below to view details:
GenesisCare - St Andrews
Adelaide, Australia
Breast Cancer Research Centre
Nedlands, Australia
Icon Cancer Centre Southport
Southport, Australia
Sydney Adventist Hospital
Wahroonga, Australia
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Who is running the clinical trial?
Celcuity Inc
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
| Participant Group/Arm | Intervention/Treatment |
|---|---|
EXPERIMENTAL: Arm A: Gedatolisib + Palbociclib + Fulvestrant
| Drug: Arm A: Gedatolisib + Palbociclib + Fulvestrant |
ACTIVE_COMPARATOR: Arm B: Ribociclib + Fulvestrant
| Drug: Arm B: Ribociclib + Fulvestrant |
EXPERIMENTAL: Arm C: Gedatolisib + Palbociclib + Letrozole
| Drug: Arm C: Gedatolisib + Palbociclib + Letrozole |
ACTIVE_COMPARATOR: Arm D: Ribociclib + Letrozole
| Drug: Arm D: Ribociclib + Letrozole |
What is the study measuring?
Primary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Progression Free Survival (PFS) | Progression Free Survival (PFS) in Patients with PIK3CA ND and PIK3CA MT Breast Cancer PFS is defined as the time from randomization to death or the first documented progression, whichever occurs first, confirmed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria, as determined based on blinded independent central review (BICR) | From date of randomization to the date of death due to any cause, up to approximately 48 months |
Secondary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival (OS) in Patients with PIK3CA ND and PIK3CA MT Breast Cancer | OS is defined as the length of time from randomization until the date of death from any cause method, where PFS is defined as the time from randomization to death or the first documented progression, whichever occurs first, confirmed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria, as determined based on blinded independent central review (BICR) | From date of randomization to the date of death due to any cause, up to approximately 48 months |
| Overall Response Rate (ORR) in Patients with PIK3CA ND and PIK3CA MT Breast Cancer | Percentage of subjects who achieved an objective response according to RECIST v1.1 criteria (complete response \[CR\] or partial response \[PR\]) as assessed by BICR) | Up to approximately 48 months |
| Overall Response Rate (ORR) in Patients with PIK3CA ND and PIK3CA MT Breast Cancer | Percentage of subjects who achieved an objective response according to RECIST v1.1 (CR or PR) as assessed by BICR | Up to approximately 48 months |
| Duration of Response (DOR) in Patients with PIK3CA ND and PIK3CA MT Breast Cancer | Time from the assessment of initial response (PR or better) to death or first documented radiologically confirmed disease progression as assessed by BICR, whichever occurs first | Up to approximately 48 months |
| Time to Response (TTR) in Patients with PIK3CA ND and PIK3CA MT Breast Cancer | Time to Response (TTR) in Patients with PIK3CA ND and PIK3CA MT Breast Cancer | Time from randomization to the first assessment of PR or better as assessed by BICR |
| Clinical Benefit Rate (CBR) in Patients with PIK3CA ND and PIK3CA MT Breast Cancer | Percentage of subjects with CR or PR; or with stable disease (SD) lasting \>24 weeks as assessed by BICR | Up to approximately 48 months |
| Quality of Life (QOL) Functional Assessment of Cancer Therapy - Breast Trial Outcome Index (FACT-B TOI) | Questions in Patients with PIK3CA ND and PIK3CA MT Breast Cancer | From baseline to 30 Day Safety Follow-up |
| Adverse Events | Type, incidence, severity (as graded by the NCI CTCAE v5.0), seriousness, and relationship to study medications of Adverse Events and any laboratory abnormalities in Arm A compared with Arm B | Up to approximately 48 months |
References
Clinical Trials Gov: Phase 3 Study of Gedatolisib as First-Line Treatment for Patients With HR-Positive, HER2-Negative Advanced Breast Cancer (VIKTORIA-2)Other trials to consider
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