Recruiting NCT06757634

Phase 3 Study of Gedatolisib as First-Line Treatment for Patients With HR-Positive, HER2-Negative Advanced Breast Cancer (VIKTORIA-2)

Phase III Interventional Breast Cancer

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied: The protocol lists: Arm A: Gedatolisib + Palbociclib + Fulvestrant, Arm B: Ribociclib + Fulvestrant, Arm C: Gedatolisib + Palbociclib + Letrozole, Arm D: Ribociclib + Letrozole.
Who it may be relevant to: Registry conditions: Breast Cancer. Basic parameters: from 18 years · All.
What needs checking: Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place: United States, Argentina, Australia, Belgium, Brazil +17
Next step: Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

VIKTORIA-2: A Randomized, Open-Label, Phase 3 Study Evaluating Efficacy and Safety of Gedatolisib With Endocrine Therapy and Palbociclib vs Endocrine Therapy and Ribociclib as First-Line Treatment in Patients With HR-Positive and HER2-Negative Advanced Breast Cancer

Overview

This is a Phase 3, open-label, randomized, clinical trial evaluating the efficacy and safety of gedatolisib and palbociclib plus endocrine therapy for the treatment of patients with locally advanced or metastatic HR+/HER2- advanced breast cancer.

Detailed description

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).

Interventions

Drug Arm A: Gedatolisib + Palbociclib + Fulvestrant
Drug: Gedatolisib Participants will receive intravenous (IV) gedatolisib once weekly for 3 weeks (Days 1, 8, 15) followed by 1 week off Other Names: • PF-05212384 Drug: Palbociclib Participants will receive oral palbociclib on days 1-21 of each 28-day cycle. Other Names: • IBRANCE Drug: Fulvestrant Participants will receive intramuscular (IM) fulvestrant every 2 weeks during Cycle 1 and then every 4 weeks Other Names: • Faslodex
Drug Arm B: Ribociclib + Fulvestrant
Drug: Ribociclib Participants will receive oral ribociclib on Days 1-21 of each 28-day cycle Other Names: • KISQALI® Drug: Fulvestrant Participants will receive intramuscular (IM) fulvestrant approximately every 2 weeks during Cycle 1 then approximately every 4 weeks Other Names: • Faslodex
Drug Arm C: Gedatolisib + Palbociclib + Letrozole
Drug: Gedatolisib Participants will receive intravenous (IV) gedatolisib once weekly for 3 weeks (Days 1, 8, 15) followed by 1 week off Drug: Palbociclib Participants will receive oral palbociclib on days 1-21 of each 28-day cycle. Drug: Letrozole Participants will receive oral letrozole daily.
Drug Arm D: Ribociclib + Letrozole
Drug: Ribociclib Participants will receive oral ribociclib on Days 1-21 of each 28-day cycle Drug: Letrozole Participants will receive oral letrozole daily.

Primary outcome measures

Progression Free Survival (PFS) [Time frame: From date of randomization to the date of death due to any cause, up to approximately 48 months]

Secondary outcome measures (7)

Overall Survival (OS) [Time frame: From date of randomization to the date of death due to any cause, up to approximately 48 months]
Overall Response Rate (ORR) [Time frame: Up to approximately 48 months]
Duration of Response (DOR) [Time frame: Up to approximately 48 months]
Time to Response (TTR) [Time frame: Time from randomization to the first assessment of PR or better as assessed by BICR]
Clinical Benefit Rate (CBR) [Time frame: Up to approximately 48 months]
Quality of Life (QOL) Functional Assessment of Cancer Therapy - Breast Trial Outcome Index (FACT-B TOI) [Time frame: From baseline to 30 Day Safety Follow-up]
Adverse Events [Time frame: Up to approximately 48 months]

Eligibility criteria

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 endocrine therapy (ET) or progression of disease after 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 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

i. Study 1: if disease progression was on or within event occurred >6 months of discontinuation after completion of CDK4/6 inhibitor portion of treatment.

ii. Study 2: if disease progression event occurred >12 months after completion of CDK4/6 inhibitor portion of treatment.

Subject has radiologically measurable disease according to RECIST v1.1, per local assessment. Patients with nonmeasurable 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 or any other selective estrogen receptor degrader (SERD), except fulvestrant, used in (neo)adjuvant setting.
Prior treatment with systemic anticancer therapy for ABC
Subjects with type 1 diabetes, or uncontrolled type 2 diabetes requiring daily insulin therapy.
Known and untreated, or active, brain or leptomeningeal metastases
History of clinically significant cardiovascular abnormalities
Known, clinically significant ophthalmic conditions
History of drug-induced symptomatic interstitial lung disease (pneumonitis) or hepatitis

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation: Randomized
Model: Parallel assignment
Masking: Open label
Primary purpose: Treatment