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

Trial Summary

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.

What data supports the effectiveness of the MUC1 Vaccine + Aromatase Inhibitor treatment for breast cancer?

The research highlights that aromatase inhibitors (AIs) are effective in treating postmenopausal women with hormone receptor-positive breast cancer, often used either alone or after tamoxifen, and have become a standard part of treatment. However, the specific effectiveness of the MUC1 Vaccine in combination with AIs for breast cancer is not directly addressed in the provided studies. ^{1 2 3 4 5}

What makes the MUC1 Vaccine + Aromatase Inhibitor treatment unique for breast cancer?

The MUC1 Vaccine + Aromatase Inhibitor treatment is unique because it combines a vaccine targeting the MUC1 protein, which is often overexpressed in cancer cells, with aromatase inhibitors that reduce estrogen levels, potentially enhancing the immune response against breast cancer cells. ^{2 6 7 8 9}

What is the purpose of this trial?

Post-menopausal women with biopsy-proven DCIS will be enrolled into two cohorts. One cohort will receive neoadjuvant therapy with an aromatase inhibitor alone for about 12 weeks prior to surgery at 12 weeks. The second cohort will receive neoadjuvant therapy with an aromatase inhibitor and MUC1 vaccination (MUC1 peptide + Hiltonol®) pre-operatively at baseline, and weeks 2 and 10, followed by surgery at about 12 weeks. Patients in the vaccine cohort will be offered an optional boost vaccine 6 months after surgery.

Research Team

Emilia J. Diego

Principal Investigator

UPMC Magee Women's Hospital

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Endocrine therapy for early breast cancer. [2015]

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

Initial versus sequential adjuvant aromatase inhibitor therapy: a review of the current data. [2018]

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

Advances in adjuvant endocrine therapy for postmenopausal women. [2013]

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

Hormonal therapy for postmenopausal breast cancer: the science of sequencing. [2013]

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

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

6. England pubmed.ncbi.nlm.nih.gov

Comparative clinical pharmacology and pharmacokinetic interactions of aromatase inhibitors. [2019]

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

Ovarian Function Recovery During Anastrozole in Breast Cancer Patients With Chemotherapy-Induced Ovarian Function Failure. [2022]

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

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

9. Germany pubmed.ncbi.nlm.nih.gov

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