Guadecitabine + Durvalumab for Liver and Pancreatic Cancer

Recruiting at 2 trial locations

Overseen By Ramona Lujan, RN

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Southern California

Must be taking: Antivirals

Must not be taking: Immunosuppressants, Hypomethylating agents

Disqualifiers: Autoimmune disease, Organ transplant, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 1

Duration: 28 days per cycle

55 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This phase Ib trial studies the side effects and best dose of guadecitabine and how well it works when given together with durvalumab in treating patients with liver, pancreatic, bile duct, or gallbladder cancer that has spread to other places in the body. Guadecitabine may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as durvalumab, may block tumor growth in different ways by targeting certain cells. Giving guadecitabine and durvalumab may work better in treating patients with liver, pancreatic, bile duct, or gallbladder cancer.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you cannot be on other investigational agents or certain immunosuppressive medications. It's best to discuss your specific medications with the trial team.

What is known about the safety of Guadecitabine and Durvalumab in humans?

Durvalumab, also known as Imfinzi or MEDI4736, has been studied in various cancers and generally shows a manageable safety profile, but it can cause side effects like liver injury, hepatitis (liver inflammation), nephritis (kidney inflammation), dermatitis (skin inflammation), and myocarditis (heart inflammation). Liver injury during treatment is linked to poorer survival, and myocarditis, although rare, can be severe. ^{1 2 3 4 5}

How is the drug combination of Guadecitabine and Durvalumab unique for liver and pancreatic cancer?

The combination of Guadecitabine and Durvalumab is unique because it combines a DNA methylation inhibitor (Guadecitabine) with an immune checkpoint inhibitor (Durvalumab), which may enhance the immune system's ability to fight cancer cells. This approach is novel for liver and pancreatic cancer, where standard treatments are limited. ^{1 2 3 6 7}

What data supports the effectiveness of the drug Durvalumab for liver and pancreatic cancer?

Durvalumab has shown effectiveness in treating various cancers, including advanced biliary tract cancer, where it improved survival rates when combined with other drugs. It is also approved for use in lung cancer and urothelial carcinoma, indicating its potential in treating different types of solid tumors. ^{1 2 3 6 7}

Who Is on the Research Team?

Anthony El-Khoueiry, MD

Principal Investigator

University of Southern California

Are You a Good Fit for This Trial?

This trial is for adults with advanced liver, pancreatic, bile duct, or gallbladder cancer that has spread. Participants must be able to follow the study plan and have certain blood counts and organ functions within specific ranges. They should not be pregnant or breastfeeding and must use contraception. People who've had certain other treatments or conditions like inflammatory bowel disease, another primary malignancy within 3 years, uncontrolled brain metastases, or a history of severe immune-related side effects from previous immunotherapy are excluded.

Inclusion Criteria

My hemoglobin level is at least 8.0 g/dL, or it has been maintained at this level for over a week after a transfusion.

Your liver enzymes (AST and ALT) should not be more than 2.5 times the normal limit, unless you have liver metastases or chronic liver disease (hepatitis), in which case they should not be more than 5 times the normal limit.

My kidney function, measured by creatinine clearance, is good.

Exclusion Criteria

You have a history of a weakened immune system from birth.

Patients may not be receiving any other investigational agents

Patients must not be nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive guadecitabine subcutaneously once daily on days 1-5 and durvalumab intravenously on day 8. Courses repeat every 28 days.

28 days per cycle

1 visit per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

Every 2 months

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab
• Guadecitabine

Trial Overview The trial is testing the combination of guadecitabine (which may block enzymes needed for tumor cell growth) with durvalumab (a monoclonal antibody targeting cancer cells). It aims to determine the best dose and assess how well these drugs work together against various types of advanced cancers when they have spread beyond their original location.

How Is the Trial Designed?

Group I: Treatment (guadecitabine, durvalumab) Experimental Treatment 2 Interventions

Patients receive guadecitabine SC QD on days 1-5 and durvalumab IV over 60 minutes on day 8. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Durvalumab is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as Imfinzi for:

• Locally advanced, unresectable non-small cell lung cancer (NSCLC)

Approved in United States as Imfinzi for:

• Extensive-stage small cell lung cancer (ES-SCLC)
• Limited-stage small cell lung cancer (LS-SCLC)
• Locally advanced or metastatic urothelial carcinoma

Approved in Japan as Imfinzi for:

• Not specified in provided sources

Who Is Running the Clinical Trial?

University of Southern California

Lead Sponsor

Trials

956

Recruited

1,609,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Van Andel Research Institute

Collaborator

Trials

28

Recruited

5,200+

Published Research Related to This Trial

Durvalumab, a PD-L1 inhibitor, has been shown to be safe for patients with various solid tumors, with common side effects including pruritus and fatigue, based on a meta-analysis of 17 studies involving 1,529 patients.

Higher levels of PD-L1 expression in tumors are linked to better treatment responses to durvalumab, indicating that PD-L1 could serve as a useful biomarker for predicting the drug's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. Yang, H., Shen, K., Zhu, C., et al.[2022]

Durvalumab is an FDA-approved monoclonal antibody that enhances T-cell responses against cancer by blocking the PD-L1 pathway, specifically for patients with advanced urothelial carcinoma who have progressed after platinum-based chemotherapy.

The drug is currently being tested in phase III trials for various cancers, including lung and head and neck cancers, indicating its potential broad application in oncology beyond urothelial carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab: First Global Approval. Syed, YY.[2022]

In a study of 112 patients receiving durvalumab for cancer treatment, 19% experienced liver injury, which was linked to higher rates of tumor progression and mortality, indicating that liver injury may be a significant concern in this patient population.

Among the liver injury cases, 29% were classified as probable drug-induced liver injury (DILI) related to durvalumab, but these cases were generally mild and self-limited, suggesting that while monitoring for liver injury is important, severe complications are rare.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liver injury during durvalumab-based immunotherapy is associated with poorer patient survival: A retrospective analysis. Swanson, LA., Kassab, I., Tsung, I., et al.[2023]

In a study of 442 patients with unresectable stage III non-small cell lung cancer (NSCLC) who received platinum-based chemoradiotherapy, 50.3% were found eligible for durvalumab consolidation immunotherapy (CIT) according to PACIFIC trial criteria.

Despite only half of the patients meeting eligibility criteria, 85.6% of those eligible received CIT within a year of the drug's approval, with the main reasons for ineligibility being disease progression and low PD-L1 tumor proportion scores.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Consolidation Immunotherapy After Platinum-Based Chemoradiotherapy in Patients With Unresectable Stage III Non-Small Cell Lung Cancer-Cross-Sectional Study of Eligibility and Administration Rates. Eichkorn, T., Bozorgmehr, F., Regnery, S., et al.[2022]

In the phase 3 TOPAZ-1 trial, the combination of durvalumab with gemcitabine and cisplatin significantly improved overall survival and progression-free survival in adults with advanced biliary tract cancer, compared to the placebo group.

Durvalumab's benefits were consistent across various patient factors, including tumor location and PD-L1 expression levels, and the treatment was found to be manageable in terms of tolerability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab: A Review in Advanced Biliary Tract Cancer. Fung, S., Syed, YY.[2023]

Durvalumab, a PD-L1 blocking antibody, has shown clinical efficacy and a manageable safety profile in treating advanced non-small-cell lung cancer, especially in patients with ≥25% PD-L1 expression.

The drug is being evaluated in various treatment settings, including as a monotherapy and in combination with other therapies, showing promising results particularly after chemoradiation, although lower response rates were noted in patients with EGFR and ALK mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab in non-small-cell lung cancer patients: current developments. Mezquita, L., Planchard, D.[2018]

A 67-year-old male with lung squamous cell carcinoma developed myocarditis after receiving durvalumab, a PD-L1 inhibitor, highlighting the potential for serious cardiac side effects from this treatment.

The patient's myocarditis led to a significant decrease in heart function but improved rapidly with glucocorticoid therapy, suggesting that timely intervention can effectively manage this rare but severe adverse event.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case Report: Acute Myocarditis Due to PD-L1 Inhibitor Durvalumab Monotherapy in a Patient With Lung Squamous Cell Carcinoma. Zhou, B., Li, M., Chen, T., et al.[2022]

Citations

1. New Zealand pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Durvalumab: First Global Approval. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Liver injury during durvalumab-based immunotherapy is associated with poorer patient survival: A retrospective analysis. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Consolidation Immunotherapy After Platinum-Based Chemoradiotherapy in Patients With Unresectable Stage III Non-Small Cell Lung Cancer-Cross-Sectional Study of Eligibility and Administration Rates. [2022]

5. France pubmed.ncbi.nlm.nih.gov

Durvalumab: A Review in Advanced Biliary Tract Cancer. [2023]

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

Durvalumab in non-small-cell lung cancer patients: current developments. [2018]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Case Report: Acute Myocarditis Due to PD-L1 Inhibitor Durvalumab Monotherapy in a Patient With Lung Squamous Cell Carcinoma. [2022]