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)
PHASE3ACTIVE_NOT_RECRUITING
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.
Study details:
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 advanced (inoperable) or metastatic Hormone Receptor Positive, Human Epidermal Growth Factor Receptor 2 Negative (HR+/HER2-) breast cancer following progression on or after CDK4/6 and aromatase inhibitor therapy. Gedatolisib is an intravenously administered pan-PI3K/mTOR inhibitor. Palbociclib is a CDK4/6 inhibitor.
Fulvestrant is a selective estrogen receptor degrader (SERD). Subjects will be assessed for PIK3CA status and then randomized to treatment arms according to their confirmed PIK3CA mutation status.
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 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.
Exclusion criteria
- 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.
- 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 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.
- 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.
- Known hypersensitivity to the study drugs or their components.
- Pregnant or breast-feeding women.
- Concurrent participation in another interventional clinical trial.
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
NCT05501886
Intervention or treatment
DRUG: Gedatolisib
DRUG: Palbociclib
DRUG: Fulvestrant
DRUG: Alpelisib
Conditions
- Breast Cancer
You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.
Research sites nearby
Closest Location:
Adelaide Oncology & Haematology
Select from list below to view details:
Adelaide Oncology & Haematology
Adelaide, Australia
St Vincent's Hospital (Melbourne) Ltd
Fitzroy, Australia
Peninsula & South Eastern Hematology and Oncology Group (PSEHOG)
Frankston, Australia
Hollywood Private Hospital, Breast Cancer Research Centre
Nedlands, Australia
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Who is running the clinical trial?
CI
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 - Patients Lacking PIK3CA Mutations (WT)
| Drug: Gedatolisib, Drug: Palbociclib, Drug: Fulvestrant |
EXPERIMENTAL: Arm B - Patients Lacking PIK3CA Mutations (WT)
| Drug: Gedatolisib, Drug: Fulvestrant |
ACTIVE_COMPARATOR: Arm C - Patients Lacking PIK3CA Mutations (WT)
| Drug: Fulvestrant |
EXPERIMENTAL: Arm D - Patients with PIK3CA Mutation (MT)
| Drug: Gedatolisib, Drug: Palbociclib, Drug: Fulvestrant |
ACTIVE_COMPARATOR: Arm E - Patients with PIK3CA Mutation (MT)
| Drug: Fulvestrant, Drug: Alpelisib |
EXPERIMENTAL: Arm F - Patients with PIK3CA Mutation (MT)
| Drug: Gedatolisib, Drug: Fulvestrant |
What is the study measuring?
Primary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Progression Free Survival (PFS) in Patients with PIK3CA WT 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) | Approximately 48 months |
Secondary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival (OS) in Patients with PIK3CA WT 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 WT 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 |
| Duration of Response (DOR) in Patients with PIK3CA WT and PIK3CA MT Breast Cancer | Time from the assessment of initial response (PR or better) to death or first documented disease progression as assessed by BICR, whichever occurs first | Up to approximately 48 months |
| Time to Response (TTR) in Patients with PIK3CA WT and PIK3CA MT Breast Cancer | Time form randomization to the first assessment of PR or better as assessed by BICR, whichever comes first | Up to approximately 48 months |
| Clinical Benefit Rate (CBR) in Patients with PIK3CA WT and PIK3CA MT Breast Cancer | Percentage of subjects with CR, PR, or stable disease (SD) \>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 WT and PIK3CA MT Breast Cancer | The FACT-B TOI is an abbreviated (24-item) version of the full FACT-B which focuses only on the patient's Physical Well-being (PWB), Functional Well-being (FWB), and Breast Cancer Subscale (BCS) components using a 5-level scale, (Not at all, A little bit, Some-what, Quite a bit, Very much). | From baseline to 30 Day Safety Follow-up |
| Quality of Life (QOL) NCCN-FACT Breast Symptom Index -16 (NFBSI-16) in Patients with PIK3CA WT and PIK3CA MT Breast Cancer | NCCN-FACT is derived from the FACT-B and only 4 additional items will be administered to enable optional scoring of the NFBSI subscales and total score using a 5-level scale (Not at all, A little bit, Some-what, Quite a bit, Very much). | From baseline to 30 Day Safety Follow-up |
| Patient-Reported Outcomes in Patients with PIK3CA WT and PIK3CA MT Breast Cancer | Patient-Reported Outcomes Measurement Information System (PROMIS®) Short Form v2.0 - Physical Function 8c using a 5-level scale (Without any difficulty, With a little difficulty, With some difficulty, With much difficulty, Unable to do) | From baseline to 30 Day Safety Follow-up |
| EuroQol 5 in Patients with PIK3CA WT and PIK3CA MT Breast Cancer | EuroQol 5 Dimension 5 Level (EQ-5D-5L) - This is a 5 question, self-administered visual analog scale (VAS) where patients use 0 (worst health) to 100 (best health) to indicate how they view their health. | From baseline to 30 Day Safety Follow-up |
| Adverse Events | Safety and tolerability will be evaluated by review of type, incidence, severity (as graded by the National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\] v5.0), seriousness, and relationship to study medications of adverse events (AEs) and any laboratory abnormalities | Up to approximately 48 months |
Are you running this trial?If you're a clinic or sponsor, you can claim this study.
References
Clinical Trials Gov: 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)Other trials to consider
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