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

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial evaluates the safety of a new treatment called DPX-Survivac, combined with other therapies, for women with certain types of breast cancer. Participants will receive various combinations of the treatment, including with radiation or another drug, to assess how each affects the cancer before surgery. Eligible women have breast cancer that is hormone receptor-positive and HER2-negative and have not previously received treatments like chemotherapy or hormone therapy. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

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

Research shows that using DPX-Survivac with letrozole is safe and well-tolerated for patients with early-stage HR+ breast cancer. Letrozole, a common breast cancer treatment, can sometimes cause side effects like bone weakness. DPX-Survivac, also known as MVP-S, has been found safe and can trigger an immune response in other cancer studies.

Studies suggest that DPX-Survivac remains safe when used with radiation. Adding radiation aims to enhance treatment effectiveness without increasing safety risks. Similarly, when combined with cyclophosphamide, DPX-Survivac remains safe and beneficial, as seen in other cancer studies.

This trial is in an early phase, focusing on safety assessment. The results so far are promising, but more research is needed to confirm these findings. Participation in the study contributes to this important research. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike standard breast cancer treatments that often target hormone receptors or use chemotherapy, DPX-Survivac is unique because it employs a vaccine-based approach to stimulate the immune system to attack cancer cells. Researchers are excited about this treatment because it targets survivin, a protein that helps cancer cells evade death, making it a promising method to eliminate cancer cells more effectively. Additionally, when combined with letrozole, radiation, or cyclophosphamide, this approach could provide a more comprehensive attack on the cancer by leveraging both hormonal and immune pathways. This multi-faceted strategy might offer enhanced efficacy compared to current treatment options alone.

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

Research has shown that combining DPX-Survivac with letrozole may help treat hormone receptor-positive breast cancer. Studies have found this combination safe and effective in helping the immune system attack cancer cells. Letrozole alone is known to slow breast cancer by 43%. In this trial, participants in different arms will receive additional treatments: Arm B includes radiation, and Arm C includes cyclophosphamide, alongside DPX-Survivac and letrozole. These additional treatments are generally well-tolerated and might offer extra benefits. This method uses the body's immune system, similar to successful treatments for other cancers, such as ovarian cancer. Overall, early evidence suggests this combination could effectively manage breast cancer. ^{1 3 4 6 7}

Who Is on the Research Team?

Sasha Stanton, MD

Principal Investigator

Providence Health & Services

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04895761

NCT04895761 | Neoadjuvant DPX-Survivac Aromatase ... The study seeks to establish the safety of neoadjuvant aromatase inhibitor with: DPX-Survivac, DPX-Survivac plus radiation, or DPX-Survivac with ...

2. providence.elsevierpure.com providence.elsevierpure.com/en/publications/646neoadjuvant-immunotherapy-combining-maveropepimut-s-mvp-s-with

646 Neoadjuvant immunotherapy combining ... Conclusions Combining MVP-S and letrozole is safe and well tolerated to date as neoadjuvant therapy in HR+ early-stage breast cancer. This ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.TPS1119

Neoadjuvant survivin-targeted immunotherapy ... Previous clinical trials have shown that MVP-S is well-tolerated, immunogenic, and could lead to clinical response in several cancer indications.

4. withpower.com withpower.com/trial/phase-1-breast-neoplasms-5-2021-e36d4

DPX-Survivac + Hormone/Radiation/Cyclophosphamide ... 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 ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10390884/

Maveropepimut-S, a DPX-Based Immune-Educating ... Maveropepimut-S with intermittent low-dose cyclophosphamide is well-tolerated, with clinical benefit for patients with recurrent ovarian cancer.

6. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.2022.40.16_suppl.TPS1119

Breast Cancer—Metastatic Maveropepimut-S (MVP-S, previously named DPX-Survivac) leverages the non-aqueous, lipid-based DPX delivery platform to educate a specific ...

7. jitc.bmj.com jitc.bmj.com/content/10/Suppl_2/A677

Abstract Conclusions Combining MVP-S and letrozole is safe and well tolerated to date as neoadjuvant therapy in HR+ early-stage breast cancer. This ...