Vaccine + Sargramostim for Pancreatic Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Corticosteroids, Investigational agents

Disqualifiers: Brain metastases, Uncontrolled illness, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 71 days

18 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I trial studies the side effects and best dose of vaccine therapy when given together with sargramostim in treating patients with locally advanced or metastatic pancreatic cancer that cannot be removed by surgery. Vaccines made from a gene-modified virus may help the body build an effective immune response to kill tumor cells. Colony-stimulating factors, such as sargramostim, may increase the number of immune cells found in bone marrow or peripheral blood. Giving vaccine therapy directly into the tumor together with sargramostim may cause a stronger immune response and kill more tumor cells.

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 cannot have had chemotherapy or radiotherapy within 4 weeks before starting the study. Also, you cannot be on systemic corticosteroid therapy within 28 days of registration.

What data supports the effectiveness of the treatment Vaccine + Sargramostim for Pancreatic Cancer?

While there is no direct evidence of effectiveness for this specific treatment combination, similar vaccine approaches have shown promise. For example, a personalized mRNA vaccine led to immune responses and delayed disease recurrence in some pancreatic cancer patients, suggesting potential for vaccine-based therapies. ^{1 2 3 4 5}

How does the treatment Vaccine + Sargramostim for Pancreatic Cancer differ from other treatments?

This treatment is unique because it combines a vaccine with Sargramostim, which is a growth factor that stimulates the immune system, potentially enhancing the body's ability to fight pancreatic cancer. Unlike standard treatments, this approach aims to break the tumor's immune evasion by boosting T-cell responses, which are crucial for targeting and destroying cancer cells. ^{1 3 5 6 7}

Research Team

Elizabeth Poplin, MD

Principal Investigator

Rutgers Cancer Institute of New Jersey

Eligibility Criteria

This trial is for patients with advanced pancreatic cancer that can't be surgically removed. They should have a life expectancy of at least 6 months, good physical function, and adequate organ function. Participants must not have other serious illnesses or conditions that could interfere with the study, no recent chemotherapy or radiotherapy, no brain metastases, and they must agree to use contraception.

Inclusion Criteria

My pancreatic cancer cannot be surgically removed, but it can be treated with an ultrasound-guided injection.

I will use birth control during and for four months after the study.

Patients (in the opinion of the principal investigator) should be able to complete a full 3-month course of vaccination preferably with an anticipated survival of 6 months or longer

Exclusion Criteria

I am currently experiencing symptoms of pancreatitis with high amylase or lipase levels.

I do not have HIV, hepatitis B, or hepatitis C.

I can avoid close contact with high-risk individuals for 3 weeks after getting the PANVAC-V vaccine.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive falimarev vaccine intratumorally and inalimarev vaccine subcutaneously, along with sargramostim, with a dose-escalation study design

71 days

Multiple visits for vaccine administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

Every 3 months

Long-term monitoring

Participants are monitored for T cell proliferation and cytokine production

Up to 4 years

Treatment Details

Interventions

• Falimarev
• Inalimarev
• Sargramostim

Trial Overview The trial is testing vaccine therapy using gene-modified viruses alongside sargramostim (a substance boosting white blood cells) to see if this combination prompts the body's immune system to destroy cancer cells more effectively. The vaccines are injected directly into the tumor.

Participant Groups

Group I: Treatment (vaccine therapy, sargramostim) Experimental Treatment 4 Interventions

Patients receive falimarev vaccine intratumorally using endoscopic ultrasound guidance on day 1. Patients also receive inalimarev vaccine SC on day 1 and sargramostim SC on days 1-4. Patients then receive falimarev vaccine SC on days 15 and 29 and sargramostim SC on days 15-18 and 29-32 in the absence of unacceptable toxicity. Beginning on day 43, patients with stable or improving pancreatic cancer receive falimarev vaccine SC and sargramostim SC (given on the day of and for 3 days after each falimarev vaccination) monthly in the absence of disease progression or unacceptable toxicity. Beginning on day 71, patients with no irreversible or dose limiting toxicity, receive falimarev vaccine SC and sargramostim SC (given on the day of and for 3 days after each falimarev vaccination) monthly in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

Pancreatic tumors are highly resistant to chemotherapy and are often diagnosed at advanced stages, leading to limited treatment options for patients.

Despite decades of research into vaccine therapies for pancreatic cancer, recent reviews indicate that none have successfully improved clinical outcomes, highlighting the ongoing challenges in developing effective treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trials of vaccines for pancreatic ductal adenocarcinoma: Is there any hope of an improved prognosis? Mizuguchi, T., Torigoe, T., Satomi, F., et al.[2023]

In a study of 7 patients with advanced pancreatic ductal adenocarcinoma (PDA) receiving a WT1-targeting dendritic cell vaccine combined with chemotherapy, those who responded well (super-responders) had significantly lower levels of plasma matrix metalloproteinase-9 and systemic inflammatory markers compared to non-responders.

Lower cytoplasmic expression of WT1 in PDA cells was also associated with better overall survival, suggesting that both low inflammatory responses and low WT1 expression may serve as predictive markers for patient outcomes in this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predicted Markers of Overall Survival in Pancreatic Cancer Patients Receiving Dendritic Cell Vaccinations Targeting WT1. Ito, Z., Kan, S., Bito, T., et al.[2019]

The dendritic cell (DC) vaccine modified with tumor lysate and Interleukin-18 (IL-18) significantly enhanced immune responses in a mouse model of pancreatic carcinoma, leading to higher levels of IL-18 and IFN-gamma compared to other treatment groups.

Mice treated with the DC-IL18-Lysate vaccine remained tumor-free for at least 50 days and had a median survival of over 62 days, which was significantly longer than other groups, indicating its potential efficacy as a therapeutic vaccine against pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The immunotherapeutic effect of dendritic cells vaccine modified with interleukin-18 gene and tumor cell lysate on mice with pancreatic carcinoma. Tang, ZH., Qiu, WH., Wu, GS., et al.[2019]

The Rotterdam PancrEAtic Cancer Vaccination-2 trial is investigating the safety and tolerability of a combination treatment using dendritic cell vaccines and an anti-CD40 agonistic antibody in patients with advanced pancreatic cancer, with a focus on those who have not responded to standard chemotherapy.

This phase I trial will include 12 to 18 patients and aims to assess treatment-induced immune responses and tumor-specific effects, potentially offering a new immunotherapy approach for a disease with limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tumour-specific immunological responses of combined dendritic cell vaccination and anti-CD40 agonistic antibody treatment for patients with metastatic pancreatic cancer: protocol for a phase I, open-label, single-arm, dose-escalation study (REACtiVe-2 trial). Lau, SP., van 't Land, FR., van der Burg, SH., et al.[2023]

References

1. Japan pubmed.ncbi.nlm.nih.gov

Trials of vaccines for pancreatic ductal adenocarcinoma: Is there any hope of an improved prognosis? [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Predicted Markers of Overall Survival in Pancreatic Cancer Patients Receiving Dendritic Cell Vaccinations Targeting WT1. [2019]

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

The immunotherapeutic effect of dendritic cells vaccine modified with interleukin-18 gene and tumor cell lysate on mice with pancreatic carcinoma. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Safety and tumour-specific immunological responses of combined dendritic cell vaccination and anti-CD40 agonistic antibody treatment for patients with metastatic pancreatic cancer: protocol for a phase I, open-label, single-arm, dose-escalation study (REACtiVe-2 trial). [2023]

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

Personalized mRNA Vaccine Immunogenic against PDAC. [2023]

6. Germany pubmed.ncbi.nlm.nih.gov

Gastrin vaccine improves response to immune checkpoint antibody in murine pancreatic cancer by altering the tumor microenvironment. [2020]

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

An ISCOM vaccine combined with a TLR9 agonist breaks immune evasion mediated by regulatory T cells in an orthotopic model of pancreatic carcinoma. [2020]