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

Trial Summary

What is the purpose of this trial?

This trial is testing a special vaccine made from a patient's own immune cells to help fight breast cancer that has spread to the brain and spinal cord. The goal is to find the safest highest dose that can be given.

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.

What data supports the effectiveness of the treatment Dendritic Cell Vaccine for Breast Cancer?

Research shows that dendritic cell vaccines can trigger the body's immune system to attack breast cancer cells, with studies indicating they can induce a strong immune response and potentially improve survival in certain breast cancer patients. Additionally, similar vaccines have shown promising results in other cancers like melanoma, suggesting potential benefits for breast cancer treatment. ^{1 2 3 4 5}

Is the dendritic cell vaccine for breast cancer safe for humans?

The dendritic cell vaccine, tested under various conditions, has been generally well-tolerated in humans. Studies show it causes mild side effects like local inflammation that subsides quickly, with no severe organ or autoimmune toxicity observed. ^{1 2 5 6 7}

How is the Dendritic Cell Vaccine treatment for breast cancer different from other treatments?

The Dendritic Cell Vaccine (DCV) for breast cancer is unique because it uses the patient's own immune cells, called dendritic cells, which are trained to recognize and attack cancer cells, potentially leading to a more targeted and less toxic treatment compared to conventional therapies. ^{1 2 4 8 9}

Research Team

Peter Forsyth, MD

Principal Investigator

Moffitt Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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]

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]

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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

An autologous dendritic cell vaccine polarizes a Th-1 response which is tumoricidal to patient-derived breast cancer cells. [2020]

2. Netherlands 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. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Improved overall survival in dendritic cell vaccination-induced immunoreactive subgroup of advanced melanoma patients. [2018]

4. Germany pubmed.ncbi.nlm.nih.gov

Autologous dendritic cell vaccine for estrogen receptor (ER)/progestin receptor (PR) double-negative breast cancer. [2022]

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

Allogeneic breast cancer cell vaccines. [2020]

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

Active immunotherapy for cancer patients using tumor lysate pulsed dendritic cell vaccine: a safety study. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Vaccination with melanoma lysate-pulsed dendritic cells, of patients with advanced colorectal carcinoma: report from a phase I study. [2020]

8. England 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. [2021]

9. Korea (South) 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. [2021]