MUC1 Vaccine + Aromatase Inhibitor for Breast Cancer

Overseen By Lucia Borrasso, BS

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: Finn, Olivera, PhD

Must be taking: Aromatase inhibitors

Must not be taking: Steroids, Immunomodulators

Disqualifiers: Invasive cancer, Autoimmune disease, others

Stay on Your Current Meds You can continue your current medications while participating

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach for treating ductal carcinoma in situ (DCIS) in post-menopausal women. Researchers aim to determine if combining a MUC1 vaccine (a type of immunotherapy) with an aromatase inhibitor (a drug that lowers estrogen) before surgery is more effective than using the drug alone. Participants will be divided into two groups: one will receive only the aromatase inhibitor, while the other will receive both the inhibitor and the vaccine. Women who have undergone menopause, have DCIS confirmed by biopsy, and are planning surgery may be suitable for this trial. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

If you are currently on hormone replacement therapy, selective estrogen receptor modulator therapy, or aromatase inhibitor therapy, you will need to stop these medications for 30 days before starting the trial. Other medications, like steroids or immunomodulators, may also need to be stopped, but the protocol does not specify all medications.

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

Research has shown that the MUC1 vaccine, which targets a protein called mucin-1 found in many breast cancer patients, has been tested alongside other treatments. Studies have found that this vaccine is generally safe when combined with standard cancer therapies, with no major safety issues reported.

Aromatase inhibitors, common treatments for breast cancer, have FDA approval for other uses. They are usually well-tolerated, with generally manageable side effects.

Overall, both treatments are considered safe and usually well-tolerated, but individual experiences can vary. Discussing potential risks and benefits with healthcare providers is crucial before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the MUC1 peptide vaccine with adjuvant Hiltonol for breast cancer because it introduces a novel approach to treatment by targeting the MUC1 protein, which is often overexpressed in breast cancer cells. Unlike standard treatments like aromatase inhibitors that focus on reducing estrogen levels, this vaccine aims to boost the immune system to specifically attack cancer cells. This immune-based approach could potentially enhance treatment efficacy and offer a new line of defense against breast cancer, complementing existing therapies.

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

Research shows that the MUC1 vaccine, one of the treatments studied in this trial, has shown promising results when combined with other treatments. For instance, women who received the MUC1-targeting vaccine tecemotide with chemotherapy experienced better outcomes. Their chance of remaining free from disease recurrence was 81.9%, compared to 65.0% for those who did not receive the vaccine. Additionally, the vaccine increased the chance of staying free from invasive disease to 71.3%, compared to 59.8% for those who did not receive it. However, another study found that while the vaccine was safe, it did not significantly enhance treatment effects when used alone. This trial will evaluate the MUC1 vaccine in combination with an aromatase inhibitor, which may offer additional benefits. These findings suggest that the MUC1 vaccine could be beneficial, especially when combined with other therapies. ^{1 3 4 6 7}

Who Is on the Research Team?

Emilia J. Diego

Principal Investigator

UPMC Magee Women's Hospital

Are You a Good Fit for This Trial?

This trial is for post-menopausal women who have been diagnosed with a type of breast cancer known as Ductal Carcinoma In Situ (DCIS). The key eligibility criteria are not provided, but typically participants would need to meet certain health standards and agree to the treatment schedule.

Inclusion Criteria

AST and ALT <= 2.5X ULN

Total bilirubin <=1.5X the ULN; <=2x ULN for patients with Gilbert's disease

I have DCIS that might be starting to spread, based on a biopsy.

Exclusion Criteria

I haven't had a second cancer in the last 5 years, except for certain skin or cervical cancers.

I am on hormone therapy but can stop it for 30 days before the study's first test.

I do not have active hepatitis B or C, or if I have antibodies, my virus levels are undetectable.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Therapy

Participants receive neoadjuvant therapy with an aromatase inhibitor alone or with MUC1 vaccination prior to surgery

12 weeks

3 visits (in-person) for the vaccine cohort at baseline, week 2, and week 10

Surgery

Participants undergo surgery after completing neoadjuvant therapy

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 1 year

Regular follow-up visits as per study protocol

Optional Boost Vaccine

Participants in the vaccine cohort may receive an optional boost vaccine 6 months after surgery

1 week

What Are the Treatments Tested in This Trial?

Interventions

• MUC1 Peptide Vaccine

Trial Overview The study is testing two approaches in treating DCIS. One group will receive an aromatase inhibitor alone, while the other will get both an aromatase inhibitor and a new MUC1 peptide vaccine combined with Hiltonol® before surgery. There's also an optional booster shot of the vaccine six months after surgery.

How Is the Trial Designed?

Group I: MUC1 vaccine + adjuvant Hiltonol + Aromatase Inhibitor Experimental Treatment 3 Interventions

MUC1 peptide vaccine with poly-ICLC adjuvant Hiltonol administered subcutaneously (SQ) Anastrozole 1 mg, letrozole 2.5 mg, or exemestane 25 mg by mouth daily

Group II: Aromatase Inhibitor Active Control 1 Intervention

Anastrozole 1 mg, letrozole 2.5 mg, or exemestane 25 mg by mouth daily

MUC1 Peptide Vaccine is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Tecemotide for:

• Non-small cell lung cancer

Approved in United States as Stimuvax for:

• Non-small cell lung cancer

Approved in Canada as BLP25 for:

• Non-small cell lung cancer

Who Is Running the Clinical Trial?

Finn, Olivera, PhD

Lead Sponsor

Trials

1

Recruited

50+

A Glimmer of Hope Foundation

Collaborator

Trials

1

Recruited

50+

Breast Cancer Research Foundation

Collaborator

Trials

79

Recruited

40,500+

Published Research Related to This Trial

Third-generation aromatase inhibitors (AIs) like anastrozole, letrozole, and exemestane have emerged as effective alternatives to tamoxifen for treating postmenopausal breast cancer, particularly in hormone receptor-positive cases, as shown in the ATAC trial with over five years of follow-up.

Fulvestrant, a new type of estrogen receptor antagonist with no partial agonist activity, represents a promising option in breast cancer treatment, and the review discusses future sequencing strategies for using AIs earlier in treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New developments in the treatment of postmenopausal breast cancer. Howell, A.[2018]

Aromatase inhibitors (AIs) have become a standard treatment for postmenopausal women with hormone receptor-positive breast cancer, showing improved outcomes compared to the traditional 5-year tamoxifen regimen.

Despite the effectiveness of AIs, many patients still experience recurrences, particularly more than 5 years after diagnosis, indicating a need for personalized treatment strategies and novel approaches for high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in adjuvant endocrine therapy for postmenopausal women. Lin, NU., Winer, EP.[2013]

Endocrine therapies, including tamoxifen, aromatase inhibitors, and selective estrogen receptor modulators, are effective in treating ER-positive breast cancer in postmenopausal women, helping to prolong treatment benefits and delay tumor recurrence.

Current evidence suggests that while combining different endocrine therapies may not be more effective than using aromatase inhibitors alone, sequential use of aromatase inhibitors after tamoxifen can provide additional benefits, highlighting the need for further clinical trials to optimize treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hormonal therapy for postmenopausal breast cancer: the science of sequencing. Miller, WR., Bartlett, JM., Canney, P., et al.[2013]

In a study of 329 postmenopausal women with chemotherapy-induced ovarian function failure, the rate of ovarian function recovery during treatment with aromatase inhibitors (AIs) was found to be 12.4% over 30 months, indicating a notable risk of recovery even in older patients.

Women who experienced ovarian function recovery had significantly higher estradiol levels during AI treatment compared to those who did not, suggesting that higher estradiol levels may impact the efficacy of AIs in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ovarian Function Recovery During Anastrozole in Breast Cancer Patients With Chemotherapy-Induced Ovarian Function Failure. van Hellemond, IEG., Vriens, IJH., Peer, PGM., et al.[2022]

Aromatase inhibitors (AIs) like anastrozole and letrozole show a significant disease-free survival benefit over tamoxifen when used as upfront therapy, especially in patients with node-positive breast cancer.

Both upfront AI therapy and sequential switching from tamoxifen to AI are considered cost-effective, with similar safety profiles, but upfront AI therapy may be particularly advantageous for higher-risk patients to reduce early relapse rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial versus sequential adjuvant aromatase inhibitor therapy: a review of the current data. Ellis, MJ., Rigden, CE.[2018]

Adjuvant tamoxifen therapy has significantly reduced mortality rates in women with estrogen receptor-positive early breast cancer, indicating its effectiveness as a treatment.

The future of breast cancer treatment may involve aromatase inhibitors, but individual patient characteristics and tumor profiles will need to be considered to optimize therapy, suggesting a move towards personalized treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endocrine therapy for early breast cancer. Hussain, SA., Williams, S., Stevens, A., et al.[2015]

Adjuvant endocrine therapy, particularly with tamoxifen and aromatase inhibitors, has significantly improved survival rates in early-stage, estrogen receptor-positive breast cancer, with large trials supporting both 'up-front' and 'switch' treatment strategies.

Extended adjuvant therapy is being explored for women at ongoing risk of recurrence beyond 5 years, but the optimal duration of treatment remains debated, highlighting the need for personalized approaches based on individual risk and potential toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Controversies in adjuvant endocrine therapy for breast cancer. Johnston, SR.[2020]

Letrozole is more effective than anastrozole in inhibiting aromatase at clinically used doses, leading to greater suppression of estrogen levels, which is crucial for treating early breast cancer.

All three aromatase inhibitors (anastrozole, letrozole, exemestane) show high specificity and effectiveness in reducing estrogen production, but exemestane has a minor androgenic effect that affects sex hormone binding globulin levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative clinical pharmacology and pharmacokinetic interactions of aromatase inhibitors. Boeddinghaus, IM., Dowsett, M.[2019]

Third-generation aromatase inhibitors like letrozole, anastrozole, and exemestane effectively reduce estrogen levels in post-menopausal patients to 5%-10% of baseline, which is significantly lower than the 20%-30% reduction achieved by earlier drugs like 4-hydroxyandrostenedione.

Ongoing studies are evaluating the effectiveness of these newer aromatase inhibitors in various treatment sequences for breast cancer, while also addressing concerns about their potential cardiovascular and bone-related side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aromatase inhibitors and their use in the adjuvant setting. Coombes, RC.[2019]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.587

Addition of the MUC-1 vaccine tecemotide to neoadjuvant ... Women who had received chemotherapy + tecemotide had a particularly good outcome with a DRFS of 81.9% vs 65.0% (HR 0.50, 95% CI 0.31 – 0.83, p= ...

2. aacrjournals.org aacrjournals.org/clincancerres/article/31/12_Supplement/PS3-03/754032

Vaccination with MUC-1-targeting tecemotide improves ... Participants who had received chemotherapy + tecemotide had a particularly favorable outcome with an IDFS of 71.3% vs 59.8% (HR 0.69, 95% CI ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4514140/

Tecemotide: An antigen-specific cancer immunotherapy Although no antitumor responses were observed, median survival time was 5.4 months in patients receiving 20 μg compared to 14.6 months in patients treated with ...

4. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT00640861?draw=2&rank=1

Vaccine Therapy in Treating Patients With Previously ... To describe the impact of immunization on clinical outcomes in patients with MUC1-positive breast cancer in terms of disease-free survival and overall survival.

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0959804920301593

Efficacy and safety of the therapeutic cancer vaccine ... Largest vaccine trial in preoperative treatment of early breast cancer. · MUC-1–based tecemotide vaccine is safe but did not show an improved treatment effect ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32325419/

Efficacy and safety of the therapeutic cancer vaccine ... The glycoprotein mucin-1 (MUC-1) is overexpressed in more than 90% of BC patients, and is targeted by the cancer vaccine tecemotide.

7. ascopubs.org ascopubs.org/doi/pdf/10.1200/JCO.2024.42.16_suppl.587

Addition of the MUC-1 vaccine tecemotide to neoadjuvant ... Conclusions: The MUC-1 vaccine tecemotide, when added to standard neoadjuvant systemic therapy, markedly improved DRFS and OS. Despite the exploratory nature ...