Novel Biomarker-Driven Therapies for Breast Cancer

(EVOLVE-BDT Trial)

EL
AG
Overseen ByAna Gallegos
Age: 18+
Sex: Any
Trial Phase: Phase 2
Sponsor: UNC Lineberger Comprehensive Cancer Center
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new treatments for specific types of metastatic breast cancer that have spread to other parts of the body. It focuses on breast cancer that is either estrogen receptor-positive (ER+) and hormone receptor-negative or triple-negative (lacking three common receptors). Based on certain biomarkers—molecules in the body that can indicate disease—participants will receive different treatments to determine which works best. These treatments include antiandrogen therapy, capecitabine (a chemotherapy drug), and combinations of SERD (selective estrogen receptor degrader) with abemaciclib or everolimus. Suitable candidates have metastatic breast cancer that fits one of these profiles and have not started most second-line therapies yet. The trial aims to help researchers understand the effectiveness of these treatments and gather important data to guide future care. As a Phase 2 trial, this research measures how well the treatment works in an initial, smaller group of people, offering participants a chance to contribute to advancements in cancer care.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that several treatments tested in this trial have been safe in earlier studies.

For antiandrogens, studies indicate they effectively treat certain types of breast cancer and have a good safety record. Specifically, enobosarm, a particular antiandrogen, demonstrated its ability to fight tumors in patients with a certain type of advanced breast cancer without major safety issues.

Capecitabine, another treatment under consideration, is a type of chemotherapy generally well-tolerated. Previous studies showed it significantly helps breast cancer patients, with manageable side effects.

The combination of a SERD (Selective Estrogen Receptor Degrader) with abemaciclib has also proven safe. Research suggests it effectively treats a specific type of breast cancer, with predictable and manageable side effects.

Similarly, combining a SERD with everolimus has maintained a good safety record. Studies highlighted its effectiveness in treating advanced breast cancer, with known and manageable side effects.

Lastly, the combination of a SERD with either everolimus or capecitabine has been studied, showing these treatments are well-tolerated. Research indicates these combinations can help patients with advanced breast cancer live longer without the disease worsening.

Overall, these treatments have shown safety in previous studies, suggesting they may be well-tolerated in clinical settings. Joining a clinical trial would provide more insights into their safety and effectiveness.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for breast cancer because they are tailored specifically to the genetic makeup of the cancer cells. Unlike standard treatments, which often include chemotherapy or hormone therapy, these investigational therapies use selective estrogen receptor degraders (SERDs) combined with drugs like abemaciclib or everolimus to target specific mutations in estrogen receptor-positive (ER+) breast cancers. For triple-negative breast cancer, a challenging subtype, the inclusion of antiandrogens offers a novel approach by targeting androgen receptors. This personalized strategy aims to improve outcomes by directly addressing the unique characteristics of different breast cancer subtypes.

What evidence suggests that this trial's treatments could be effective for metastatic breast cancer?

This trial will explore various treatment arms for breast cancer. Antiandrogens, which participants may receive, have demonstrated a 6-month clinical benefit rate (CBR) of 29% in previous studies for androgen receptor-positive triple-negative breast cancer (TNBC), with some patients benefiting for over a year. Capecitabine-based chemotherapy, another treatment option, has significantly improved response rates and progression-free survival in advanced breast cancer, though its effect on overall survival remains unclear.

The trial will also investigate SERD combined with abemaciclib, which improved outcomes in previous studies, showing a 7-year overall survival rate of 86.8% in early breast cancer. Another arm will study SERD combined with everolimus, which reduced the risk of disease progression or death and improved progression-free survival in advanced ER-positive, HER2-negative breast cancer. Lastly, the combination of everolimus with capecitabine, also under study, has shown promise in delaying cancer progression and improving overall survival, making these treatment options strong candidates for managing specific breast cancer subtypes.678910

Who Is on the Research Team?

LA

Lisa A Carey, MD

Principal Investigator

UNC Lineberger Comprehensive Cancer Center

EW

Eric Winer, MD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for adults over 18 with metastatic breast cancer that's either estrogen receptor-positive/hormone receptor-negative or triple-negative. They must be able to follow the study plan and have an ECOG performance status of 0-2, meaning they can care for themselves and are up and about more than half of the day.

Inclusion Criteria

I have signed the consent form and agreed to share my health information for the study.
I am willing and able to follow the study's requirements.
I am 18 years old or older.
See 2 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive biomarker-directed therapies based on their subtype, with liquid biopsy collected on Cycle 2 Day 1 and at each re-staging

Until progression, toxicity, or physician discretion
Regular visits for treatment and re-staging assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 12 months

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

  • Antiandrogen
  • Capecitabine
  • SERD* + abemaciclib
  • SERD* + everolimus
  • SERD* + everolimus or capecitabine

Trial Overview

The trial tests different combinations of drugs (SERD* with abemaciclib, everolimus, capecitabine) against standard treatments based on tumor biomarkers in patients. It includes collecting data from past treatments, current medical records, tumor tissue samples, and blood tests before starting treatment.

How Is the Trial Designed?

6

Treatment groups

Experimental Treatment

Active Control

Group I: Cohort 4Experimental Treatment1 Intervention
Group II: Cohort 2 Arm BExperimental Treatment1 Intervention
Group III: Cohort 2 Arm AExperimental Treatment1 Intervention
Group IV: Cohort 1- Arm BExperimental Treatment1 Intervention
Group V: Cohort 1 Arm AExperimental Treatment1 Intervention
Group VI: Cohort 3Active Control1 Intervention

Find a Clinic Near You

Who Is Running the Clinical Trial?

UNC Lineberger Comprehensive Cancer Center

Lead Sponsor

Trials
377
Recruited
95,900+

Breast Cancer Research Foundation

Collaborator

Trials
79
Recruited
40,500+

Translational Breast Cancer Research Consortium

Collaborator

Trials
27
Recruited
3,100+

Advanced Research Projects Agency for Health (ARPA-H)

Collaborator

Citations

Efficacy of antiandrogens in androgen receptor-positive triple ...

CBR at 6 months was 29 % (7/24) with 2 CR, 3 PR and 2 SD. Four patients had a clinical benefit >12 months. Real-life efficacy of AA use in metastatic AR + TNBC ...

Efficacy of antiandrogens in androgen receptor-positive ...

The patients who received an antiandrogen as the first-line treatment had a 6-month CBR of 57% (4/7) versus 18% (3/17) when administered in the second or ...

Advances of androgen receptor in triple-negative breast ...

The findings indicated disease-free survival (DFS) rates of 94%, 92%, and 80% at 1, 2, and 3 years, respectively, although the median OS data ...

Darolutamide or capecitabine in triple-negative, androgen ...

Analysis of tumours from the START trial showed that MAhigh tumours respond better than other subtypes of breast cancer to treatment with ...

Androgen receptor‐positive, triple‐negative breast cancer

Among the 30 patients deemed evaluable for the primary endpoint, the CBR at 6 months was 20%, with 1 CR and 5 cases of SD reported at ≥6 months.

Anti-Androgenic Therapies Targeting the Luminal ...

The literature aims to explore anti-androgenic particulars against luminal androgen receptor-specific triple-negative breast cancer.

Activity and safety of enobosarm, a novel, oral, selective ...

Enobosarm has anti-tumour activity in patients with ER-positive, HER2-negative advanced breast cancer, showing that AR activation can result in clinical ...

Targeting Androgen Receptor in Treating HER2 Positive ...

Our data revealed that inhibiting AR impairs the growth of HER2 + breast cancer cells in vitro and vivo, in comparable to the effect of ...

The Role of Androgen Receptor and Antiandrogen ...

The function of the AR in breast cancer is not uniform; it is a pleiotropic actor whose role is dictated by the specific molecular context of the tumor. A.

Endocrine therapy-based treatments in hormone receptor ...

We assessed the efficacy of different ET-based treatments in patients with hormone receptor-positive/HER2-negative advanced breast cancer with endocrine- ...