Gedatolisib + Fulvestrant +/- Palbociclib for Advanced Breast Cancer

(VIKTORIA-1 Trial)

Recruiting at 217 trial locations

Overseen By Nadene Zack, MS

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Celcuity Inc

Must be taking: LHRH agonists

Must not be taking: PI3K inhibitors, Akt inhibitors

Disqualifiers: Diabetes, Brain metastases, Cardiovascular, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial is testing a combination of drugs to treat advanced breast cancer that has not responded to other treatments. The drugs work by blocking growth signals, breaking down estrogen receptors, and stopping cell division. Tamoxifen is a commonly used drug that blocks estrogen receptors to treat breast cancer, but resistance to it often develops.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must not have had certain treatments like PI3K inhibitors or more than two lines of endocrine therapy for advanced disease.

What data supports the effectiveness of the drug combination of Gedatolisib, Fulvestrant, and Palbociclib for advanced breast cancer?

The combination of palbociclib and fulvestrant has been shown to significantly improve progression-free survival in women with hormone receptor-positive, HER2-negative advanced breast cancer, as demonstrated in a clinical trial where patients lived longer without their cancer worsening compared to those who received fulvestrant alone. ^{1 2 3 4 5}

Is the combination of Gedatolisib, Fulvestrant, and Palbociclib safe for humans?

Palbociclib combined with Fulvestrant has been studied in women with advanced breast cancer, showing that while it can cause side effects like low white blood cell counts (neutropenia), infections, and fatigue, these are generally manageable. The treatment is considered to have a favorable safety profile, meaning it is generally safe for use in humans when monitored properly. ^{1 6 7 8 9}

What makes the drug combination of Gedatolisib, Fulvestrant, and Palbociclib unique for advanced breast cancer?

This drug combination is unique because it combines Gedatolisib, which targets multiple pathways involved in cancer cell growth, with Fulvestrant, an estrogen receptor blocker, and Palbociclib, a CDK4/CDK6 inhibitor that helps stop cancer cell division. This multi-targeted approach may offer a more comprehensive treatment for advanced breast cancer compared to using these drugs individually. ^{1 2 4 7 10}

Research Team

Nadene Zack

Principal Investigator

Celcuity Inc

Eligibility Criteria

This trial is for adults with advanced or metastatic HR+/HER2- breast cancer who've progressed after CDK4/6 and aromatase inhibitor therapy. They must have a life expectancy of at least 3 months, ECOG status of 0-1, adequate organ function, and no pregnancy. Pre-menopausal women must agree to LHRH agonist treatment.

Inclusion Criteria

I am a pre/peri-menopausal woman willing to start LHRH agonist treatment.

I can provide a recent or past sample of my tumor for PIK3CA mutation testing.

My blood, liver, kidneys, and clotting functions are all working well.

Exclusion Criteria

Known hypersensitivity to the study drugs or their components

My cancer is only in the bones and does not affect soft tissues.

My cancer has spread to my organs and is causing symptoms that could quickly become life-threatening.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive gedatolisib plus fulvestrant with or without palbociclib based on PIK3CA mutation status

48 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

Treatment Details

Interventions

• Alpelisib (PI3K Inhibitor)
• Fulvestrant (Estrogen Receptor Antagonist)
• Gedatolisib (PI3K/mTOR Inhibitor)
• Palbociclib (CDK4/6 Inhibitor)

Trial Overview The study tests gedatolisib plus fulvestrant with or without palbociclib against standard care in patients whose breast cancer has worsened despite previous treatments. It's an open-label Phase 3 trial where participants are randomly assigned to different drug combinations.

Participant Groups

Group I: Arm F - Patients with PIK3CA Mutation (MT) Experimental Treatment 2 Interventions

Gedatolisib + Fulvestrant

Group II: Arm D - Patients with PIK3CA Mutation (MT) Experimental Treatment 3 Interventions

Gedatolisib + Palbociclib + Fulvestrant

Group III: Arm B - Patients Lacking PIK3CA Mutations (WT) Experimental Treatment 2 Interventions

Gedatolisib + Fulvestrant

Group IV: Arm A - Patients Lacking PIK3CA Mutations (WT) Experimental Treatment 3 Interventions

Gedatolisib + Palbociclib + Fulvestrant

Group V: Arm E - Patients with PIK3CA Mutation (MT) Active Control 2 Interventions

Alpelisib + Fulvestrant

Group VI: Arm C - Patients Lacking PIK3CA Mutations (WT) Active Control 1 Intervention

Fulvestrant

Fulvestrant is already approved in Canada, Japan for the following indications:

Approved in Canada as Faslodex for:

• Hormone receptor-positive metastatic breast cancer
• Locally advanced breast cancer

Approved in Japan as Faslodex for:

• Hormone receptor-positive metastatic breast cancer
• Locally advanced breast cancer

Who Is Running the Clinical Trial?

Celcuity Inc

Lead Sponsor

Trials

9

Recruited

1,600+

Celcuity, Inc.

Lead Sponsor

Trials

7

Recruited

920+

Findings from Research

Palbociclib, when combined with fulvestrant, significantly improves progression-free survival in women with hormone receptor-positive, HER2-negative advanced breast cancer, showing a median PFS of 9.5 months compared to 4.6 months with placebo, based on a study of 521 women.

The safety profile of palbociclib includes common adverse reactions such as neutropenia and infections, which were observed in over 20% of patients, confirming its known side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval of Palbociclib in Combination with Fulvestrant for the Treatment of Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer. Walker, AJ., Wedam, S., Amiri-Kordestani, L., et al.[2022]

In a phase II study involving 190 postmenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer, the combination of palbociclib and fulvestrant significantly improved one-year progression-free survival (PFS-1y) rates (83.5% vs. 71.9% for placebo) and median PFS (31.8 months vs. 22.0 months).

While the palbociclib/fulvestrant combination showed better efficacy, it was associated with higher rates of grade 3-4 adverse events, particularly neutropenia (68.1% vs. 0% in the placebo group), indicating a need for careful monitoring of side effects in patients receiving this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase II study of fulvestrant plus palbociclib or placebo in endocrine-sensitive, hormone receptor-positive/HER2-advanced breast cancer: GEICAM/2014-12 (FLIPPER). Albanell, J., Martínez, MT., Ramos, M., et al.[2022]

In a study of 521 premenopausal and postmenopausal patients with endocrine-resistant metastatic breast cancer, those treated with palbociclib and fulvestrant showed a higher rate of prolonged benefit (29%) compared to those on placebo and fulvestrant (15%).

Long-term responders to palbociclib-fulvestrant tended to have less disease burden at baseline and lower rates of certain mutations, but no specific molecular or clinical factors were identified as predictors of long-term benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of prolonged benefit from palbociclib plus fulvestrant in women with endocrine-resistant hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer in PALOMA-3. Cristofanilli, M., DeMichele, A., Giorgetti, C., et al.[2022]

In a study of 54 postmenopausal women with metastatic breast cancer, fulvestrant demonstrated clinical benefit in 38.9% of patients, with a median time to progression of 6.4 months, indicating its efficacy even after multiple prior treatments.

Fulvestrant was well tolerated, with no severe toxicities (grade 3/4) reported, suggesting it is a safe option for patients with advanced breast cancer who have limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant ('Faslodex') in heavily pretreated postmenopausal patients with advanced breast cancer: single centre clinical experience from the compassionate use programme. Mlineritsch, B., Psenak, O., Mayer, P., et al.[2018]

Palbociclib, when combined with letrozole or fulvestrant, significantly improves progression-free survival and overall survival in women with hormone receptor-positive (HR+)/HER2-negative advanced breast cancer, based on clinical trials.

The treatment has a manageable tolerability profile, with neutropenia being the most common side effect, and does not negatively impact quality of life, making it a valuable option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib in metastatic breast cancer: current evidence and real-life data. Serra, F., Lapidari, P., Quaquarini, E., et al.[2020]

Oral palbociclib is an effective treatment for HR-positive, HER2-negative advanced or metastatic breast cancer, significantly prolonging progression-free survival when used with letrozole or fulvestrant in clinical trials involving postmenopausal women.

The most common side effect was neutropenia, which was manageable and rarely led to serious complications, indicating that palbociclib can be safely administered without significantly compromising its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib: A Review in HR-Positive, HER2-Negative, Advanced or Metastatic Breast Cancer. Kim, ES., Scott, LJ.[2022]

Palbociclib, in combination with letrozole, is FDA-approved for treating postmenopausal women with hormone-receptor-positive, HER2-negative advanced breast cancer, showing its efficacy as an initial therapy.

The combination of palbociclib with fulvestrant has been found to provide better outcomes than fulvestrant alone for patients who have previously progressed on endocrine therapy, highlighting its potential in advanced treatment scenarios.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib: a first-in-class CDK4/CDK6 inhibitor for the treatment of hormone-receptor positive advanced breast cancer. Lu, J.[2022]

Palbociclib, the first oral CDK4/6 inhibitor, significantly improves median progression-free survival in advanced ER-positive/HER2-negative breast cancer, showing 24.8 months with letrozole compared to 14.5 months with placebo, and 9.2 months with fulvestrant compared to 3.8 months with placebo.

The main side effect of palbociclib is neutropenia, which can be managed through dose adjustments, resulting in a favorable safety profile and delayed deterioration of quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib-The First of a New Class of Cell Cycle Inhibitors. Schmidt, M., Sebastian, M.[2018]

In a study involving 108 premenopausal women with advanced breast cancer, palbociclib combined with fulvestrant and goserelin significantly improved median progression-free survival (PFS) to 9.5 months compared to 5.6 months with placebo, indicating its efficacy in this population.

The treatment was well-tolerated, with common side effects including neutropenia and infections, but it did not interfere with ovarian suppression from goserelin, suggesting it could be a viable option to delay chemotherapy for women with endocrine-resistant disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib Combined with Fulvestrant in Premenopausal Women with Advanced Breast Cancer and Prior Progression on Endocrine Therapy: PALOMA-3 Results. Loibl, S., Turner, NC., Ro, J., et al.[2022]

Fulvestrant was well tolerated and provided clinical benefit to 21% of heavily pre-treated postmenopausal women with advanced breast cancer, with 42% achieving stable disease for at least 12 weeks.

The efficacy of fulvestrant was similar whether given after disease progression or as maintenance therapy, with a median time to progression of 3 months and no significant toxicities reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant in heavily pre-treated patients with advanced breast cancer: results from a single compassionate use programme centre. Catania, C., Ascione, G., Adamoli, L., et al.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

FDA Approval of Palbociclib in Combination with Fulvestrant for the Treatment of Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Randomized phase II study of fulvestrant plus palbociclib or placebo in endocrine-sensitive, hormone receptor-positive/HER2-advanced breast cancer: GEICAM/2014-12 (FLIPPER). [2022]

3. England pubmed.ncbi.nlm.nih.gov

Predictors of prolonged benefit from palbociclib plus fulvestrant in women with endocrine-resistant hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer in PALOMA-3. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Fulvestrant ('Faslodex') in heavily pretreated postmenopausal patients with advanced breast cancer: single centre clinical experience from the compassionate use programme. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Palbociclib in metastatic breast cancer: current evidence and real-life data. [2020]

6. France pubmed.ncbi.nlm.nih.gov

Palbociclib: A Review in HR-Positive, HER2-Negative, Advanced or Metastatic Breast Cancer. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Palbociclib: a first-in-class CDK4/CDK6 inhibitor for the treatment of hormone-receptor positive advanced breast cancer. [2022]

8. Germany pubmed.ncbi.nlm.nih.gov

Palbociclib-The First of a New Class of Cell Cycle Inhibitors. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Palbociclib Combined with Fulvestrant in Premenopausal Women with Advanced Breast Cancer and Prior Progression on Endocrine Therapy: PALOMA-3 Results. [2022]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Fulvestrant in heavily pre-treated patients with advanced breast cancer: results from a single compassionate use programme centre. [2018]