Darolutamide + Standard Therapy for Breast Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Vandana Abramson

Must be taking: Chemotherapy, Immunotherapy

Disqualifiers: Metastatic disease, Other malignancies, Heart disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 30

Duration: 24 weeks

51 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding darolutamide to the usual treatment can shrink tumors before surgery for individuals with a specific type of breast cancer. The usual treatment includes chemotherapy, which kills or stops cancer cells from growing, and immunotherapy, which helps the immune system attack the cancer. Researchers are testing darolutamide to see if it can further prevent cancer growth by blocking hormones that fuel the cancer. Individuals with stage II-IIIA androgen receptor-positive triple-negative breast cancer, who have a tumor larger than 1 cm, might be suitable for this trial. As a Phase 2 trial, this research measures how well the treatment works in an initial, smaller group, offering participants a chance to contribute to important advancements in cancer therapy.

Will I have to stop taking my current medications?

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

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

Research has shown that darolutamide is generally safe. Only a few patients have needed to lower their dose due to side effects. Specifically, one study found that just 4.5% of patients with non-metastatic prostate cancer had to reduce their dose because of side effects. Additionally, darolutamide has significantly improved survival rates without causing serious side effects compared to a placebo.

Pembrolizumab, another component of the treatment being tested, is commonly used in cancer treatment. Most people tolerate it well, though some may experience side effects like tiredness, skin rash, or diarrhea. Proper care can usually manage these side effects.

Overall, existing research considers both darolutamide and pembrolizumab safe, but monitoring for any side effects during the trial is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine standard chemotherapy and immunotherapy with darolutamide, which is typically known for treating prostate cancer. Unlike current breast cancer treatments, which mainly involve chemotherapy and immunotherapy, darolutamide is an androgen receptor inhibitor. This means it targets hormone pathways that might be playing a role in breast cancer growth. By adding darolutamide to the mix, there's potential to tackle the cancer from a different angle, possibly improving outcomes for patients.

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

This trial assigns participants to different treatment arms to evaluate the effectiveness of darolutamide combined with standard therapies. Previous studies have shown promising results for darolutamide in patients with certain types of cancer. Specifically, about 24.5% of patients taking darolutamide experienced benefits at 16 weeks, with many seeing tumor shrinkage or halted disease progression. In this trial, Arm B explores the effects of adding darolutamide to standard chemotherapy and immunotherapy. Early findings suggest that this combination might make tumors smaller and easier to remove during surgery. ^{1 6 7 8 9}

Who Is on the Research Team?

Vandana G Abramson

Principal Investigator

Vanderbilt University/Ingram Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with stage II-IIIA androgen receptor positive triple-negative breast cancer. Participants should be suitable for standard chemotherapy and immunotherapy before surgery. Those who have received prior treatments for this cancer or have other conditions that could interfere with the study are likely excluded.

Inclusion Criteria

I have signed and understand the consent form for this study.

Women must not be breastfeeding and agree to not breastfeed during study treatment and for at least 120 days after completion of treatment

I am 18 years old or older.

Exclusion Criteria

Recipient of previous allogeneic tissue/solid organ transplant

I do not have conditions that prevent the use of checkpoint inhibitors.

My breast cancer cannot be surgically removed or has spread to other parts of my body.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive standard chemotherapy and immunotherapy, with or without darolutamide, over multiple cycles before surgery

24 weeks

Regular visits for IV administration and monitoring

Surgery

Participants undergo surgery to remove the tumor after neoadjuvant therapy

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Follow-up visits at 30-37 days, 6 months, 12 months, then yearly

What Are the Treatments Tested in This Trial?

Interventions

• Darolutamide
• Pembrolizumab

Trial Overview The trial is testing if adding darolutamide, an androgen receptor inhibitor, to standard pre-surgery therapy (chemo like carboplatin, paclitaxel, doxorubicin, cyclophosphamide; immunotherapy like pembrolizumab) makes tumors smaller compared to standard therapy alone in treating triple-negative breast cancer.

How Is the Trial Designed?

Group I: Arm B (Standard chemotherapy + immunotherapy + darolutamide) Experimental Treatment 12 Interventions

Patients receive darolutamide PO BID for 14 days in the absence of disease progression or unacceptable toxicity. Patients then receive darolutamide PO BID, pembrolizumab IV over 30 minutes on day 1 of each cycle, and paclitaxel IV on days 1, 8, and 15 of each cycle, and carboplatin IV on days 1, 8, and 15 of each cycle. Cycles repeat every 21 days for up to 4 cycles (cycles 1-4) in the absence of disease progression or unacceptable toxicity. Then, patients receive pembrolizumab IV over 30 minutes, cyclophosphamide IV, and doxorubicin IV or epirubicin IV on day 1 of subsequent cycles. Cycles repeat every 21 days for up to an additional 4 cycles (cycles 5-8) in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo surgery on study, as well as US or MRI, blood sample collection, and breast biopsies throughout the study.

Group II: Arm A (Standard chemotherapy + immunotherapy) Active Control 11 Interventions

Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle, paclitaxel IV on days 1, 8, and 15 of each cycle, and carboplatin IV on days 1, 8, and 15 of each cycle. Cycles repeat every 21 days for up to 4 cycles (cycles 1-4) in the absence of disease progression or unacceptable toxicity. Then, patients receive pembrolizumab IV over 30 minutes, cyclophosphamide IV, and doxorubicin IV or epirubicin IV on day 1 of subsequent cycles. Cycles repeat every 21 days for up to an additional 4 cycles (cycles 5-8) in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo surgery on study, as well as US or MRI, blood sample collection, and breast biopsies throughout the study.

Who Is Running the Clinical Trial?

Vandana Abramson

Lead Sponsor

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(24)00737-X/fulltext

Darolutamide or capecitabine in triple-negative, androgen ... Median overall survival was 17·7 months (95% CI 11·1–not reached) in the darolutamide group and 18·1 months (95% CI: 11·3–not reached) in the ...

2. annalsofoncology.org annalsofoncology.org/article/S0923-7534(22)02103-2/fulltext

213MO Primary endpoint analysis of a randomized phase II ... A clinical benefit was observed in D arm in 13 of 53 evaluable pts (CBR at 16 weeks 24.5%; 95% CI: 12.9%-36.1%) including 2 PR and 1 CR and in C arm in 11 of 23 ...

3. ascopubs.org ascopubs.org/doi/10.1200/OP.2024.20.10_suppl.399

US real-world utilization and outcomes of darolutamide ... PSA response, OS & MFS rates were numerically higher for DARO vs ENZA & APA. TEAEs occurred in 25% of pts on DARO, 28% on ENZA & 30% on APA.

4. targetedonc.com targetedonc.com/view/darolutamide-continues-to-show-strong-efficacy-in-nmcrpc-after-3-years-regardless-of-prior-therapy

Darolutamide Continues to Show Strong Efficacy in ... In all darolutamide-treated patients, the 3-year survival rate was 82.6%. In comparison, patients given placebo had a 3-year survival rate of ...

5. pharmacytimes.com pharmacytimes.com/view/darolutamide-plus-adt-shows-strong-efficacy-and-quality-of-life-benefits-in-mhspc-without-need-for-docetaxel

Darolutamide Plus ADT Shows Strong Efficacy and Quality ... Darolutamide combined with ADT significantly and clinically improved tumor control, delaying time to CRPC (castration-resistant disease) and ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e17108

Real world outcomes of darolutamide efficacy and safety in ... Adverse events led to dose reductions in 4.5% (n=6) of nmHSPC and 1.8% (n=1) of mHSPC patients. Surgical data for 51.1% (n=68) of nmHSPC ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S095980492300360X

Efficacy and safety outcomes of darolutamide in patients ... Darolutamide significantly improved median metastasis-free survival by nearly 2 years and reduced the risk of death by 31% versus placebo, with a favourable ...

8. onclive.com onclive.com/view/darolutamide-demonstrates-long-term-safety-in-nmcrpc

Darolutamide Demonstrates Long-term Safety in nmCRPC At the final analysis, darolutamide significantly reduced the risk of death by 31% compared with placebo. Patients who still had no evidence of ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10911916/

Efficacy and Safety of Darolutamide in Combination With ... In the ARASENS trial, darolutamide in combination with androgen-deprivation therapy (ADT) and docetaxel significantly reduced the risk of death.