DPX-Survivac + Hormone/Radiation/Cyclophosphamide for Breast Cancer

Recruiting at 1 trial location

Overseen By Tracy Kelly

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: Providence Health & Services

Must be taking: Aromatase inhibitors

Must not be taking: Tamoxifen, Chemotherapy

Disqualifiers: HIV, Hepatitis B, Hepatitis C, 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)

Compensation: Varies

Number of Visits: 11

6 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a cancer vaccine combined with radiation or low-dose chemotherapy, plus hormone therapy, in women with certain types of breast cancer. The goal is to boost the immune system, reduce tumor recurrence, and slow tumor growth.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must be at least 28 days post systemic steroids before enrolling. You will also need to take letrozole daily during the trial.

What data supports the effectiveness of the drug letrozole in the treatment of breast cancer?

Letrozole has been shown to improve disease-free survival in postmenopausal women with hormone receptor-positive early breast cancer, and it was found to be more effective than tamoxifen in treating advanced breast cancer, leading to longer time before disease progression. ^{1 2 3 4 5}

Is letrozole safe for use in breast cancer treatment?

Letrozole is generally considered safe for use in breast cancer treatment, but it may cause side effects like bone fractures, osteoporosis (weakening of bones), and a higher risk of heart attack compared to tamoxifen. It is important to discuss these potential risks with your doctor. ^{1 2 3 6 7}

What makes the DPX-Survivac treatment unique for breast cancer?

DPX-Survivac is unique because it combines an innovative cancer vaccine (DPX-Survivac) with hormone therapy (Letrozole) and other treatments, potentially enhancing the immune system's ability to target cancer cells, which is different from traditional chemotherapy or hormone therapy alone. ^{2 5 8 9 10}

Research Team

Sasha Stanton, MD

Principal Investigator

Providence Health & Services

Eligibility Criteria

This trial is for post-menopausal women with resectable, non-metastatic breast cancer that's hormone receptor positive and HER2 negative. Participants should have a tumor larger than 1 cm, be at least 18 years old with good performance status, and have adequate organ function. They must not have had previous breast cancer treatments or certain other conditions.

Inclusion Criteria

I can have an MRI as per my doctor's assessment.

I understand the study details and am willing to sign the consent form.

Your recent blood tests should show that you have enough white blood cells, hemoglobin, neutrophils, lymphocytes, and platelets. Your kidney and liver function should also be within normal limits.

Exclusion Criteria

I cannot take aromatase inhibitors for my condition.

I have had breast cancer or used tamoxifen or aromatase inhibitors before.

You have used experimental immune therapy in the past.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive neoadjuvant therapy with Letrozole, DPX-Survivac, and either radiation or cyclophosphamide

6 weeks

Weekly visits for treatment administration

Surgery

Standard of care surgery is performed

2-3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Visits at Week 11 and 6 months post-surgery

Treatment Details

Interventions

• Cyclophosphamide
• DPX-Survivac
• Letrozole
• XRT 10Gy x2

Trial Overview The study tests the safety of neoadjuvant aromatase inhibitor therapy combined with DPX-Survivac alone, DPX-Survivac plus radiation (10Gy x2), or DPX-Survivac with cyclophosphamide (50mg). Each participant will also take letrozole (2.5mg daily) during the six-week pre-surgery treatment phase.

Participant Groups

Group I: Arm C: DPX-Survivac, Letrozole, cyclophosphamide Experimental Treatment 3 Interventions

Letrozole 2.5 mg po daily, cyclophosphamide 50 mg po BID, DPX-Survivac 0.25 mL SC week 2 and Week 5

Group II: Arm B: DPX-Survivac, Letrozole, Radiation Experimental Treatment 3 Interventions

Letrozole 2.5 mg po daily, XRT 10 Gy x 2, DPX-Survivac 0.25 mL SC week 2 and Week 5

Group III: Arm A: DPX-Survivac, Letrozole Experimental Treatment 2 Interventions

Letrozole 2.5 mg po daily, DPX-Survivac 0.25 mL SC week 2 and Week 5

DPX-Survivac is already approved in United States, European Union, Canada for the following indications:

Approved in United States as DPX-Survivac for:

• None approved yet; under investigation for various cancers including ovarian cancer and diffuse large B-cell lymphoma

Approved in European Union as DPX-Survivac for:

• None approved yet; under investigation for various cancers including ovarian cancer and diffuse large B-cell lymphoma

Approved in Canada as DPX-Survivac for:

• None approved yet; under investigation for various cancers including ovarian cancer and diffuse large B-cell lymphoma

Who Is Running the Clinical Trial?

Providence Health & Services

Lead Sponsor

Trials

131

Recruited

827,000+

Findings from Research

Letrozole has been fully approved by the FDA for treating postmenopausal women with hormone receptor-positive early breast cancer, showing a significant improvement in disease-free survival compared to tamoxifen, with a hazard ratio of 0.87 in the adjuvant trial.

While letrozole is effective, it is associated with a higher risk of bone fractures and myocardial infarction compared to tamoxifen, which has its own risks such as endometrial cancer and thromboembolic events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Approval summary: letrozole (Femara® tablets) for adjuvant and extended adjuvant postmenopausal breast cancer treatment: conversion of accelerated to full approval. Cohen, MH., Johnson, JR., Justice, R., et al.[2021]

In a phase II study involving 33 women with recurrent estrogen receptor-positive ovarian cancer, letrozole showed a clinical benefit in 26% of patients, with one achieving a partial response and seven having stable disease.

Letrozole was well-tolerated, with no severe toxicities reported, and the most common side effects were mild, such as fatigue and sweating, indicating a favorable safety profile for this treatment in a challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of letrozole in the treatment of recurrent platinum- and taxane-resistant high-grade cancer of the ovary or peritoneum. Ramirez, PT., Schmeler, KM., Milam, MR., et al.[2018]

Letrozole is an effective treatment for postmenopausal women with early-stage or advanced hormone-sensitive breast cancer, showing a 43% reduction in disease recurrences when used as extended adjuvant therapy beyond standard tamoxifen treatment.

In advanced breast cancer, letrozole outperformed tamoxifen in terms of time to disease progression (9.4 months vs. 6.0 months) and has a similar tolerability profile, making it a recommended first-line therapy according to treatment guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letrozole: a review of its use in postmenopausal women with breast cancer. Simpson, D., Curran, MP., Perry, CM.[2018]

In a study of 337 postmenopausal women with ER and/or PgR positive breast cancer, letrozole demonstrated a significantly higher overall objective response rate (55%) compared to tamoxifen (36%) after four months of treatment.

Letrozole also showed superior results in secondary endpoints, including ultrasound response (35% vs. 25%) and mammographic response (34% vs. 16%), while both treatments were well tolerated, indicating letrozole's effectiveness as a preoperative therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative treatment of postmenopausal breast cancer patients with letrozole: A randomized double-blind multicenter study. Eiermann, W., Paepke, S., Appfelstaedt, J., et al.[2022]

In the BIG 1-98 trial, letrozole demonstrated a 19% reduction in the risk of disease-free survival events compared to tamoxifen, indicating its superior efficacy as an adjuvant therapy for early breast cancer.

Letrozole significantly reduced the risk of distant metastases (hazard ratio 0.73), establishing it as a standard treatment option for postmenopausal women with hormone-sensitive breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The evolving role of letrozole in the adjuvant setting: first results from the large, phase III, randomized trial BIG 1-98. Monnier, A.[2022]

References

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

Approval summary: letrozole (Femara® tablets) for adjuvant and extended adjuvant postmenopausal breast cancer treatment: conversion of accelerated to full approval. [2021]

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

Superiority of letrozole to tamoxifen in the first-line treatment of advanced breast cancer: evidence from metastatic subgroups and a test of functional ability. [2018]

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

Efficacy of letrozole in the treatment of recurrent platinum- and taxane-resistant high-grade cancer of the ovary or peritoneum. [2018]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Letrozole: a review of its use in postmenopausal women with breast cancer. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Preoperative treatment of postmenopausal breast cancer patients with letrozole: A randomized double-blind multicenter study. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

The evolving role of letrozole in the adjuvant setting: first results from the large, phase III, randomized trial BIG 1-98. [2022]

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

L-BLP25 vaccine plus letrozole for breast cancer: Is translation possible? [2021]

8. England pubmed.ncbi.nlm.nih.gov

Sensitization to doxorubicin resistance in breast cancer cell lines by tamoxifen and megestrol acetate. [2019]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Preoperative concurrent chemo- and endocrine therapies for women with large operable breast cancer expressing steroid hormone receptors. [2018]

10. England pubmed.ncbi.nlm.nih.gov

FemZone trial: a randomized phase II trial comparing neoadjuvant letrozole and zoledronic acid with letrozole in primary breast cancer patients. [2022]