52 Participants Needed

Evexomostat + Alpelisib + Fulvestrant for Breast Cancer

(Amelia-1 Trial)

Recruiting at 11 trial locations
DB
JM
Overseen ByJames M Shanahan
Age: 18+
Sex: Any
Trial Phase: Phase 1 & 2
Sponsor: SynDevRx, Inc.
Must be taking: Alpelisib, Capivasertib, Fulvestrant
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug combination for post-menopausal women with a specific type of advanced breast cancer. It aims to see if the new drug can reduce side effects and improve the effectiveness of existing treatments. The treatment works by blocking proteins and hormones that help cancer grow and by managing side effects like high blood sugar.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications at least 7 days before starting the treatment, specifically strong CYP3A4 inducers, inhibitors of BCRP, and sulfonylureas. If you are on these medications, you will need to discuss alternatives with your doctor.

Is the combination of Evexomostat, Alpelisib, and Fulvestrant safe for humans?

The combination of Alpelisib and Fulvestrant has been associated with high rates of side effects like high blood sugar, rash, and diarrhea, which sometimes required hospital treatment. While this combination is approved for certain types of breast cancer, its safety profile shows significant concerns, especially in real-world settings.12345

What makes the drug combination of Evexomostat, Alpelisib, and Fulvestrant unique for breast cancer treatment?

This drug combination is unique because it combines Evexomostat, a novel component, with Alpelisib and Fulvestrant, which are already used for hormone receptor-positive, HER2-negative advanced breast cancer. Alpelisib targets a specific mutation (PIK3CA) in cancer cells, while Fulvestrant blocks estrogen receptors, and the addition of Evexomostat may offer a new approach to enhance treatment effectiveness.45678

What data supports the effectiveness of the drug combination Evexomostat + Alpelisib + Fulvestrant for breast cancer?

The combination of alpelisib and fulvestrant has been shown to improve progression-free survival in patients with hormone receptor-positive, PIK3CA-mutant metastatic breast cancer, according to the SOLAR-1 study. Additionally, alpelisib has demonstrated promising activity when combined with other treatments in similar breast cancer settings.234910

Who Is on the Research Team?

MT

Medical Team

Principal Investigator

SynDevRx, Inc.

Are You a Good Fit for This Trial?

This trial is for adult women with advanced HR+/HER2- breast cancer, specifically those who have a PIK3CA mutation and are postmenopausal. Participants should not have brain malignancies or sensitivities to the drugs being tested, nor should they have uncontrolled diabetes or previous treatments with similar drugs.

Inclusion Criteria

My cancer has a PIK3CA mutation confirmed by an FDA-approved test.
I am postmenopausal.
I am fully active or can carry out light work.
See 7 more

Exclusion Criteria

I have been treated with PI3K/Akt/mTOR inhibitors or fulvestrant.
I have been diagnosed with inflammatory breast cancer.
You are allergic to evexomostat, fulvestrant, or alpelisib or any of their ingredients.
See 2 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-treatment

14-day pre-treatment phase of evexomostat plus fulvestrant before adding either alpelisib or capivasertib

2 weeks
1 visit (in-person)

Treatment

Participants receive the triplet therapy consisting of evexomostat, alpelisib or capivasertib, and fulvestrant for up to 7 cycles

6 months
Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

  • Evexomostat
Trial Overview The study tests a combination of three drugs: Evexomostat, Alpelisib, and Fulvestrant in women with a specific gene mutation linked to aggressive breast cancer. It aims to see if Evexomostat can reduce high blood sugar caused by Alpelisib and improve its effectiveness against tumors.
How Is the Trial Designed?
1Treatment groups
Experimental Treatment
Group I: EvexomostatExperimental Treatment1 Intervention
Each subject will receive repeat doses (C1, C2...) for 28-day cycles. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria is met.

Find a Clinic Near You

Who Is Running the Clinical Trial?

SynDevRx, Inc.

Lead Sponsor

Trials
3
Recruited
140+

Published Research Related to This Trial

In a retrospective analysis of 33 patients with HR+, HER2- metastatic breast cancer, the combination of alpelisib and fulvestrant showed worse outcomes in heavily pretreated patients compared to those receiving it as a first-line treatment, with significant rates of disease progression and treatment discontinuation.
Adverse effects were common, with hyperglycemia (66.7%), rash (45.5%), and diarrhea (72.7%) leading to hospitalizations and pharmacological treatment, raising concerns about the tolerability of this regimen in real-world settings.
The efficacy and safety of alpelisib in breast cancer: A real-world analysis.Miller, J., Armgardt, E., Svoboda, A.[2023]
In a study of 76 women with hormone receptor-positive, HER2-negative metastatic breast cancer, alpelisib combined with endocrine therapy demonstrated a median progression-free survival of 5.2 months, indicating its effectiveness in a real-world setting.
However, about 31.6% of patients had to permanently discontinue alpelisib due to adverse events, with hyperglycemia being the most common serious side effect, highlighting the need for careful monitoring of patients on this treatment.
A Cohort Study of the Antitumor Efficacy and Toxicity Profile of Alpelisib for Metastatic or Locally Advanced HR+, HER2- Breast Cancer: A Single-Institution Experience.Sarfraz, H., Bari, S., Whiting, J., et al.[2023]
In the NEO-ORB study involving 257 postmenopausal women with HR+ early breast cancer, the addition of alpelisib to letrozole did not significantly improve the objective response rate compared to placebo, with rates of 43% for alpelisib versus 45% for placebo in the PIK3CA-mutant cohort.
Although the primary objective was not met, the combination treatment did show a greater decrease in phosphorylated AKT levels in PIK3CA-mutant tumors, suggesting some biological activity, but overall pathologic complete response rates remained low across all groups.
A Phase II Randomized Study of Neoadjuvant Letrozole Plus Alpelisib for Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer (NEO-ORB).Mayer, IA., Prat, A., Egle, D., et al.[2023]

Citations

The efficacy and safety of alpelisib in breast cancer: A real-world analysis. [2023]
A Cohort Study of the Antitumor Efficacy and Toxicity Profile of Alpelisib for Metastatic or Locally Advanced HR+, HER2- Breast Cancer: A Single-Institution Experience. [2023]
A Phase II Randomized Study of Neoadjuvant Letrozole Plus Alpelisib for Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer (NEO-ORB). [2023]
Fulvestrant, formerly ICI 182,780, is as effective as anastrozole in postmenopausal women with advanced breast cancer progressing after prior endocrine treatment. [2022]
Incidence, risk factors, and management of alpelisib-associated hyperglycemia in metastatic breast cancer. [2023]
FDA Approval Summary: Alpelisib Plus Fulvestrant for Patients with HR-positive, HER2-negative, PIK3CA-mutated, Advanced or Metastatic Breast Cancer. [2022]
Time course and management of key adverse events during the randomized phase III SOLAR-1 study of PI3K inhibitor alpelisib plus fulvestrant in patients with HR-positive advanced breast cancer. [2022]
Fulvestrant ('Faslodex') in heavily pretreated postmenopausal patients with advanced breast cancer: single centre clinical experience from the compassionate use programme. [2018]
Fulvestrant in heavily pre-treated patients with advanced breast cancer: results from a single compassionate use programme centre. [2018]
Case studies of fulvestrant ("Faslodex") in postmenopausal women with advanced breast cancer. [2018]
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