What side effects are associated with this type of intervention?

Common treatments for pancreatic cancer, such as those involving PDE5 inhibition (tadalafil), PD-1 inhibition (pembrolizumab), CTLA-4 inhibition (ipilimumab), and Listeria-based immunotherapy (CRS-207), have a range of side effects. PDE5 inhibitors can cause headaches, flushing, and dyspepsia. PD-1 inhibitors like pembrolizumab often lead to fatigue, skin reactions, and endocrine disorders. CTLA-4 inhibitors such as ipilimumab are associated with immune-related adverse events including colitis, hepatitis, and dermatitis. Listeria-based immunotherapy can cause flu-like symptoms, including fever, chills, and myalgia. These side effects vary in severity and frequency, and patients should discuss them with their healthcare provider to manage and mitigate risks effectively.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of pancreatic cancer, though not all are directly related to the mechanisms being studied in the trial with Tadalafil, Pembrolizumab, Ipilimumab, and CRS-207. Pembrolizumab, a PD-1 inhibitor, is approved for tumors with high microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR). Ipilimumab, a CTLA-4 inhibitor, has shown efficacy in other cancers but is not specifically approved for pancreatic cancer. There are no FDA-approved treatments involving PDE5 inhibitors or Listeria-based immunotherapy for pancreatic cancer at this time.

What other types of research exist?

Promising novel alternatives for pancreatic cancer treatment in 2024 may include: 1) KRAS inhibitors, targeting common mutations in pancreatic cancer; 2) CAR-T cell therapy, which involves engineering a patient's T cells to target cancer cells; 3) Bispecific T-cell engagers (BiTEs), which direct T cells to cancer cells; 4) Oncolytic virus therapy, using viruses to selectively infect and kill cancer cells; 5) Tumor Treating Fields (TTFields), a non-invasive treatment using electric fields to disrupt cancer cell division.

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Virus Therapy

Combination Immunotherapy for Pancreatic Cancer

Phase 2

Waitlist Available

Led By Katherine Bever, MD

Research Sponsored by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Radiographic disease progression

Histologically or cytologically proven adenocarcinoma of the pancreas

Must not have

Use more than 4 g/day of acetaminophen

Surgery within the last 28 days

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 4 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a combination of four treatments on patients with advanced pancreatic cancer who did not respond to previous chemotherapy. The treatments include a drug to improve blood flow, two therapies to help the immune system fight cancer, and a vaccine to boost the immune response against cancer cells.

Who is the study for?

Adults over 18 with metastatic pancreatic cancer that's worsened after chemotherapy can join this trial. They must understand and agree to the study, have at least one measurable tumor, be in good physical condition (ECOG 0 or 1), use birth control, and have proper organ function. Exclusions include allergies to penicillin/sulfa, brain metastases, recent treatments or surgeries, uncontrolled illnesses, certain drug uses, severe hypersensitivities, significant heart disease or infections like HIV.

What is being tested?

The trial is testing a combination of drugs: Tadalafil plus immunotherapies Pembrolizumab and Ipilimumab along with CRS-207 vaccine therapy on those with advanced pancreatic cancer who've had prior chemo. It aims to assess safety and how well these work together against the cancer.

What are the potential side effects?

Possible side effects may include allergic reactions; immune-related issues affecting organs; fatigue; skin problems; hormonal changes; flu-like symptoms from CRS-207; headaches or muscle pain from Tadalafil. Each person might experience different side effects.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My cancer has worsened as shown by imaging tests.

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My cancer is a type of pancreatic cancer confirmed by lab tests.

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My cancer has spread and I've received treatment for it.

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I have at least one tumor that can be measured.

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I am fully active or have some restrictions but can still care for myself.

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I am 18 years old or older.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I use more than 4 grams of acetaminophen daily.

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I had surgery within the last 4 weeks.

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I have poor vein access for IVs.

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I have been diagnosed with HIV, Hepatitis B, or Hepatitis C.

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I have a wound, ulcer, or bone fracture that hasn't healed.

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I am not taking any strong or moderate drugs that affect liver enzymes.

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I have a serious fluid buildup in the lining of my lungs.

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I do not have any unmanaged ongoing illnesses.

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I have received a transplant from a donor.

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I am not taking any medication that stimulates guanylate cyclase.

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I have fluid buildup in my abdomen confirmed by tests.

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I have a serious heart condition.

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I have taken steroids in the past two weeks.

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I expect to need more cancer treatments while in this study.

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I have had a condition where my eye's optic nerve was damaged due to lack of blood flow.

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I use organic nitrates for my condition.

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I haven't had cancer treatment in the last 2 weeks.

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I have or had cancer spread to my brain.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 4 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~4 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 4 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Objective response rate (irORR) using immune Response Evaluation Criteria for Solid Tumors (iRECIST)

Secondary study objectives

Number of participants experiencing grade 3 or above drug-related toxicities

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Arm A - Tadalafil, Pembrolizumab, Ipilimumab, CRS-207Experimental Treatment4 Interventions

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Ipilimumab

2015

Completed Phase 3

~3070

Pembrolizumab

2017

Completed Phase 3

~2810

CRS-207

2015

Completed Phase 2

~600

Tadalafil

2014

Completed Phase 4

~3280

0 / 24Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for pancreatic cancer include various mechanisms of action that target the disease in different ways. Tadalafil, a PDE5 inhibitor, works by enhancing immune response through modulation of myeloid-derived suppressor cells. Pembrolizumab, a PD-1 inhibitor, blocks the PD-1 pathway, thereby preventing cancer cells from evading immune detection. Ipilimumab, a CTLA-4 inhibitor, enhances T-cell activation and proliferation, boosting the immune system's ability to attack cancer cells. CRS-207, a Listeria-based immunotherapy, uses a modified bacterium to stimulate a robust immune response against tumor cells. These mechanisms are crucial for pancreatic cancer patients as they offer targeted approaches to enhance the body's immune response against a typically aggressive and hard-to-treat cancer.