DCV for Breast Cancer

Recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must not be taking: Immunotherapy, High-dose methotrexate

Disqualifiers: Active infection, Organ transplantation, HIV, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 12 weeks

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness and safest dose of a Dendritic Cell Vaccine (DCV) for individuals with breast cancer that has spread to the fluid around the brain and spinal cord, known as Leptomeningeal Disease. Researchers administer the vaccine in increasing doses to determine the highest safe amount. This trial may suit individuals with triple-negative or HER2-positive breast cancer who have confirmed Leptomeningeal Disease and remain stable without needing immediate treatment for brain or spinal tumors. 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 therapy.

Will I have to stop taking my current medications?

The trial does not specify that you must stop taking your current medications. However, if your disease has progressed on your current treatment, you may continue with your systemic cancer therapies as per the investigator's discretion. You should not start a new anti-cancer agent until the 28-day safety period is completed.

Is there any evidence suggesting that the Dendritic Cell Vaccine is likely to be safe for humans?

A previous study showed that the dendritic cell vaccine (DCV) boosted the immune system in patients with HER2-expressing breast cancer. The treatment was generally safe for those patients. Another study combined DCV with chemotherapy and found it safe while enhancing the immune system's ability to fight cancer. These studies suggest that DCV is well-tolerated in patients with similar cancers. However, since the current study remains in the early stages, the full safety profile of DCV is not yet completely known. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for breast cancer, which typically include chemotherapy, targeted therapy, and hormonal therapy, the Dendritic Cell Vaccine (DCV) introduces a novel approach by using the body's immune system to fight cancer. This treatment is unique because it employs dendritic cells, a type of immune cell, that are loaded with HER2/3 peptides to specifically target cancer cells, potentially enhancing the immune response against the tumor. Additionally, the vaccine is administered intrathecally, meaning it's delivered directly into the spinal fluid, which is different from conventional methods and may allow for more direct access to cancer cells in certain areas. Researchers are excited about DCV because it represents a personalized immunotherapy that could offer a new avenue for patients who may not respond well to existing treatments.

What evidence suggests that the Dendritic Cell Vaccine might be an effective treatment for Breast Cancer with Leptomeningeal Disease?

Research has shown that dendritic cell vaccines (DCV) can help the body's immune system combat breast cancer. One study found that patients receiving DCV had a strong immune response, with some experiencing complete tumor disappearance. Another study discovered that DCV targeting the HER2 protein on cancer cells can reduce or eliminate these cancer markers. This trial will explore the effectiveness of DCV in treating breast cancer, particularly types involving HER2 proteins, using a dose escalation approach. Initial results appear promising, but further research is necessary to confirm these findings. ^{1 4 6 7 8}

Who Is on the Research Team?

Peter Forsyth, MD

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

This trial is for breast cancer patients with Leptomeningeal Disease who have malignant cells in their CSF or radiographic abnormalities of LMD. They must not be pregnant, agree to use effective contraception, and have a life expectancy of at least 8 weeks. Participants should have stable brain/spinal cord metastases if present, an ECOG performance scale ≤3, and adequate organ function.

Inclusion Criteria

My brain or spinal cord cancer is stable and doesn't need immediate treatment.

My organ functions are within normal ranges as required.

I have LMD confirmed by positive CSF test or specific radiographic signs.

Exclusion Criteria

ORGAN TRANSPLANTATION: Prior organ transplantation including allogenic stem-cell transplantation.

I have not received a live vaccine in the last 30 days.

Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

HER2/3 peptide-pulsed DC1 will be administered intrathecally weekly for 6 doses per cycle for a maximum of two cycles, with dose escalation to find the maximum tolerated dose

12 weeks

Weekly visits for 6 doses per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment, including progression-free survival and overall survival

Up to 12 months

What Are the Treatments Tested in This Trial?

Interventions

• Dendritic Cell Vaccine

Trial Overview The study is testing the safety and highest tolerable dose of Dendritic Cell Vaccine (DCV) in breast cancer patients with Leptomeningeal Disease. It involves administering DCV through a device that allows access to the cerebrospinal fluid.

How Is the Trial Designed?

Group I: Dendritic Cell (DC) Vaccine dose escalation Experimental Treatment 1 Intervention

HER2/3 peptide-pulsed DC1 will be administered intrathecally (IT) weekly for 6 doses /cycle for a maximum of two cycles, and then re-staged. If there are sufficient DC1s this may be continued weekly thereafter. There are 1 safety cohort (1 million DCV cells) and 3 escalating doses (2 million, 10 million and 50 million DCV cells) possible.

Dendritic Cell Vaccine is already approved in United States, European Union for the following indications:

Approved in United States as Sipuleucel-T for:

• Metastatic castration-resistant prostate cancer

Approved in European Union as Autologous dendritic cell vaccine for:

• Pancreatic cancer (Orphan Drug status)
• Mesothelioma (Orphan Drug status)

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Published Research Related to This Trial

An autologous dendritic cell (DC) vaccine developed for breast cancer showed promising in vitro efficacy, eliciting a strong cytotoxic T-lymphocyte response against autologous breast cancer cells in 12 female patients with early-stage disease.

The matured DCs demonstrated significant upregulation of activation markers and produced high levels of the cytokine IL12-p70, indicating their potential effectiveness in stimulating the immune response, and they maintained viability and safety after cryopreservation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An autologous dendritic cell vaccine polarizes a Th-1 response which is tumoricidal to patient-derived breast cancer cells. Tomasicchio, M., Semple, L., Esmail, A., et al.[2020]

The study involved breast cancer patients who received dendritic cell vaccines made from their own tumor lysates, showing no serious adverse effects and a strong immune response with increased Th1 cytokine secretion and NK cells.

Patients who received the DC vaccine had a significantly longer 3-year progression-free survival rate (76.9%) compared to those who did not receive the vaccine (31.0%), indicating its potential effectiveness in delaying disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous dendritic cell vaccine for estrogen receptor (ER)/progestin receptor (PR) double-negative breast cancer. Qi, CJ., Ning, YL., Han, YS., et al.[2022]

The autologous tumour lysate dendritic cell vaccine (ADC) did not show a significant improvement in progression-free survival (PFS) or overall survival (OS) compared to best supportive care (BSC) in patients with metastatic colorectal cancer, with median PFS of 2.7 months for ADC versus 2.3 months for BSC.

Despite the lack of clinical benefit, ADC successfully induced a tumour-specific T-cell response in 84% of patients, suggesting potential for immune activation, but the study concluded that ADC alone is not effective enough to warrant further phase III trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II randomised trial of autologous tumour lysate dendritic cell plus best supportive care compared with best supportive care in pre-treated advanced colorectal cancer patients. Caballero-Baños, M., Benitez-Ribas, D., Tabera, J., et al.[2021]

The study demonstrates that fusing autologous dendritic cells (DCs) with allogeneic MCF-7 breast cancer cells can effectively stimulate T lymphocyte responses, which are crucial for targeting and killing breast cancer cells.

This approach addresses the challenge of obtaining sufficient autologous tumor cells for patients with metastatic cancer, potentially enhancing the feasibility and effectiveness of dendritic cell/tumor cell fusion vaccines in immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dendritic cells fused with allogeneic breast cancer cell line induce tumor antigen-specific CTL responses against autologous breast cancer cells. Zhang, Y., Ma, B., Zhou, Y., et al.[2022]

Dendritic cells (DCs) loaded with tumor antigens from UV-irradiated breast cancer cells can effectively generate specific cytotoxic T lymphocyte (CTL) responses against breast cancer, indicating a promising approach for immunotherapy.

The study demonstrated that using allogeneic tumor antigens from the MCF-7 breast cancer cell line allows for the production of potent CTLs without the need for labor-intensive processes to obtain autologous tumor cells, making this method practical for clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alpha-Type 1 Polarized Dendritic Cells Loaded with Apoptotic Allogeneic Breast Cancer Cells Can Induce Potent Cytotoxic T Lymphocytes against Breast Cancer. Park, MH., Yang, DH., Kim, MH., et al.[2021]

The study evaluated a dendritic cell vaccine using tumor lysate in 18 patients with advanced cancers, demonstrating that the treatment was well-tolerated with minimal side effects, primarily mild local inflammation.

Out of the patients, 22% showed objective clinical responses, indicating that this immunotherapy could effectively stimulate the immune system against cancer, particularly correlated with delayed type hypersensitivity responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Active immunotherapy for cancer patients using tumor lysate pulsed dendritic cell vaccine: a safety study. Ovali, E., Dikmen, T., Sonmez, M., et al.[2020]

In a phase I trial involving six patients with advanced colorectal cancer, a vaccine using autologous dendritic cells pulsed with melanoma cell lysate was found to be safe and well tolerated, with no observed adverse effects.

The study demonstrated that the DC-based cancer vaccine, administered intradermally in five doses over ten weeks, did not cause any toxicity, suggesting a promising approach for immunotherapy in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaccination with melanoma lysate-pulsed dendritic cells, of patients with advanced colorectal carcinoma: report from a phase I study. Burgdorf, SK., Fischer, A., Claesson, MH., et al.[2020]

Allogeneic tumor cell vaccines, which use modified tumor cells from donors, have shown promising immunological and clinical effects in patients with stage IV breast cancer, indicating their potential as a safe and effective treatment option.

These vaccines are associated with low toxicity and practical advantages over autologous vaccines, making them a compelling area for further research in cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic breast cancer cell vaccines. Dols, A., Meijer, SL., Smith, JW., et al.[2020]

In a study involving 21 advanced melanoma patients, vaccination with dendritic cells (DC) pulsed with autologous tumor antigens showed promising results, particularly with matured DC (mDC), leading to a 30.7% overall response rate and various degrees of tumor response.

The treatment was well tolerated with no major toxicities reported, and positive immune responses correlated with longer overall survival, highlighting the potential of this therapeutic approach in improving outcomes for melanoma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved overall survival in dendritic cell vaccination-induced immunoreactive subgroup of advanced melanoma patients. Ridolfi, R., Petrini, M., Fiammenghi, L., et al.[2018]

Citations

1. moffitt.org moffitt.org/newsroom/news-releases/moffitt-study-finds-vaccine-may-improve-breast-cancer-treatment-outcomes/

Moffitt Study Finds Vaccine May Improve Breast Cancer ... The results showed that patients receiving the vaccine had significant immune activity, with complete tumor disappearance observed in a notable ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8716407/

Phase I Clinical Trial of an Autologous Dendritic Cell ... The outlook for patients with HER2-positive breast cancer significantly improved in 1998 with FDA approval of trastuzumab and subsequent ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04348747

NCT04348747 | Dendritic Cell Vaccines Against Her2/Her3 ... This phase IIa trial studies how well dendritic cell vaccines against Her2/Her3 and pembrolizumab work for the treatment of triple negative breast cancer or ...

4. nature.com nature.com/articles/s41523-025-00742-x

A pilot study incorporating HER2-directed dendritic cells ... Type 1 dendritic cell vaccines targeting HER2 (HER2-DC1) reinvigorates antitumor immunity which correlates with neoadjuvant therapy response.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3330145/

HER-2 Pulsed Dendritic Cell Vaccine Can Eliminate ... Results suggest vaccination against HER-2/neu is safe, well-tolerated and induces decline and or eradication of HER-2/neu expression. These findings warrant ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0753332223004730

Dendritic cell vaccines in breast cancer The results showed that autologous DCs combined with chemotherapy could restore T cell reactivity in BC patients and was safe, which makes DC a potential tumor ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT01431196

Trial With Autologous Dendritic Cell Vaccination in Patients ... The hypothesis is that the reinforcement of the immune system with the autologous dendritic cell vaccination against HER2 negative BC could increase pathologic ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34976830/

Phase I Clinical Trial of an Autologous Dendritic Cell ... Conclusions: The AdHER2 DC vaccine showed evidence of immunogenicity and preliminary clinical benefit in patients with HER2-expressing cancers, ...