Adenovirus Vector for Pancreatic Cancer

Overseen By Edward Greeno, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Masonic Cancer Center, University of Minnesota

Must not be taking: Immunosuppressants

Disqualifiers: HIV, Hepatitis B/C, Autoimmune, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for pancreatic cancer using a modified virus (adenovirus vector) injected directly into the tumor to determine the safe dosage. Researchers aim to find the dose that minimizes side effects while remaining effective. The trial involves different treatment levels to observe the body's reactions. Individuals with pancreatic cancer that hasn't spread beyond nearby lymph nodes and who can undergo certain medical procedures may be suitable candidates for this study. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial requires that at least 4 weeks have passed since your last dose of any prior therapy before receiving the study treatment. The protocol does not specify if you need to stop other current medications, so it's best to discuss this with the study team.

Is there any evidence suggesting that RGDCRAdCOX2F is likely to be safe for humans?

Research has shown that RGDCRAdCOX2F, a modified virus designed to target and destroy cancer cells, holds potential for treating pancreatic cancer. Early studies indicate that this treatment attacks cancer cells while sparing healthy ones, offering a significant safety advantage. However, this is an early-phase trial, meaning the treatment is still being tested to determine the safest dose and its tolerability. The goal is to keep serious side effects below 20% of participants. Prospective participants can be reassured that researchers focus on finding a dose that minimizes risk while maintaining effectiveness. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for pancreatic cancer?

Researchers are excited about RGDCRAdCOX2F because it offers a novel approach to treating pancreatic cancer. Unlike traditional treatments like chemotherapy and radiation, which target rapidly dividing cells broadly, RGDCRAdCOX2F uses an adenovirus vector specifically engineered to deliver a therapeutic gene directly to cancer cells. This targeted method potentially reduces damage to healthy cells, minimizing side effects. Additionally, by exploiting the COX-2 enzyme, which is overexpressed in many cancers, this treatment aims to selectively attack tumor cells, promising a more effective and precise therapy.

What evidence suggests that this treatment might be an effective treatment for pancreatic cancer?

Research has shown that RGDCRAdCOX2F uses a specially modified virus to target and destroy pancreatic cancer cells. In lab studies, this treatment effectively killed cancer cells while sparing healthy ones. Early results from similar treatments have also successfully eliminated cancer cells in all tested samples, suggesting that RGDCRAdCOX2F could be effective against pancreatic cancer. In this trial, participants will receive varying dosage levels of RGDCRAdCOX2F to assess its safety and effectiveness. The treatment aims to maintain side effects at a manageable level. ^{2 3 4 5 6}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with pancreatic adenocarcinoma that hasn't spread beyond the pancreas and regional lymph nodes. Participants can have had one prior treatment but must wait 4 weeks before joining. They need to handle an EGD procedure, as the tumor has to be reachable by endoscopic ultrasound. Those who can get pregnant or have partners who can must use two forms of birth control.

Inclusion Criteria

Participants with partners of childbearing potential must be willing to use at least two forms of effective birth control (one form must be a barrier method) for at least 1 month after Day 1

My heart and lungs are healthy based on recent exams.

My pancreatic cancer is confirmed and hasn't spread beyond the pancreas and nearby lymph nodes.

Exclusion Criteria

My cancer is not a common type of pancreatic, ampulla, bile duct, or duodenum cancer.

My tumor is near vital areas and could cause blockage or press on major vessels if it swells.

I have had a gastrojejunostomy surgery.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Single direct tumor injection of RGD modified conditionally replicative adenovirus (RGDCRAdCOX2F) to determine the maximum tolerated dose (MTD)

1 day

1 visit (in-person)

Dose Limiting Toxicity (DLT) Observation

Observation period to monitor for dose limiting toxicity, with a minimum of 28 days between cohorts

28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• RGDCRAdCOX2F

Trial Overview The study tests a single injection of RGDCRAdCOX2F, a modified virus designed to target pancreatic cancer cells. It's in Phase I to find the highest dose patients can take without serious side effects in more than 20% of cases.

How Is the Trial Designed?

Group I: Level: 3 RGDCRAdcox2F (RGD) Experimental Treatment 1 Intervention

Patients given 3x10\^12 vp/d of RGD. Enrollment begins at DL 1 in cohorts of 2 patients. A minimum of 28 days (DLT period) must separate the last patient treated in the current cohort and the 1st patient in the next cohort of 2 patients. A minimum of 21 days must separate the 1st and 2nd patient within a cohort.

Group II: Level: 2 RGDCRAdcox2F (RGD) Experimental Treatment 1 Intervention

Patients given 9x10\^11 vp/d of RGD. Enrollment begins at DL 1 in cohorts of 2 patients. A minimum of 28 days (DLT period) must separate the last patient treated in the current cohort and the 1st patient in the next cohort of 2 patients. A minimum of 21 days must separate the 1st and 2nd patient within a cohort.

Group III: Level: 1 RGDCRAdcox2F (RGD) Experimental Treatment 1 Intervention

Patients given 3x10\^11 vp/d of RGD Enrollment begins at DL 1 in cohorts of 2 patients. A minimum of 28 days (DLT period) must separate the last patient treated in the current cohort and the 1st patient in the next cohort of 2 patients. A minimum of 21 days must separate the 1st and 2nd patient within a cohort.

Group IV: Level: -1 RGDCRAdcox2F (RGD) Experimental Treatment 1 Intervention

Patients given 3x10\^10 vp/d of RGD. Safety arm. Enrollment begins at DL 1 in cohorts of 2 patients. A minimum of 28 days (DLT period) must separate the last patient treated in the current cohort and the 1st patient in the next cohort of 2 patients. A minimum of 21 days must separate the 1st and 2nd patient within a cohort.

Who Is Running the Clinical Trial?

Masonic Cancer Center, University of Minnesota

Lead Sponsor

Trials

285

Recruited

15,700+

Published Research Related to This Trial

The study successfully created an adenoviral vector that specifically targets the EphA2 receptor, which is highly expressed on pancreatic cancer cells, demonstrating improved targeting in laboratory tests with human pancreatic cancer cell lines.

Despite the promising in vitro results showing enhanced specificity and transduction of EphA2R-expressing cells, the vector did not show increased targeting effectiveness in live mouse models, indicating a gap between laboratory success and in vivo application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ephrin A2 receptor targeting does not increase adenoviral pancreatic cancer transduction in vivo. van Geer, MA., Bakker, CT., Koizumi, N., et al.[2021]

The study evaluated adenoviral vectors for gene transfer in seven human pancreatic cancer cell lines, finding that the new Ad5/35GFP vector significantly improved transfection efficiency compared to the conventional Ad5GFP vector.

Transfection efficiency was not directly linked to the expression levels of the coxsackie and adenovirus receptor (CAR) or integrins, suggesting that the chimeric fiber proteins in Ad5/35GFP enhance gene delivery through mechanisms beyond just receptor binding.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adenovirus vectors with chimeric type 5 and 35 fiber proteins exhibit enhanced transfection of human pancreatic cancer cells. Toyoda, E., Doi, R., Kami, K., et al.[2012]

A novel treatment strategy using oncolytic adenoviral mutants combined with gemcitabine significantly enhances the effectiveness of cancer therapy in pancreatic adenocarcinoma, a highly resistant cancer, as shown in both cultured cells and xenograft models.

The adenoviral mutants selectively induce apoptosis in pancreatic cancer cells while sparing normal cells, suggesting that this combination therapy could allow for lower doses of gemcitabine, reducing toxicity while maintaining efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oncolytic adenoviral mutants with E1B19K gene deletions enhance gemcitabine-induced apoptosis in pancreatic carcinoma cells and anti-tumor efficacy in vivo. Leitner, S., Sweeney, K., Oberg, D., et al.[2022]

The modified oncolytic adenovirus Ad5/3-CXCR4-E1A was found to be more effective in infecting and destroying pancreatic cancer cells compared to an unmodified version, indicating its potential as a targeted therapy.

In a study involving 40 SCID mice with pancreatic tumor xenografts, treatment with Ad5/3-CXCR4-E1A resulted in significantly smaller tumors, improved body condition, and prolonged survival, suggesting its efficacy as a new therapeutic option for pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Virotherapy using a novel chimeric oncolytic adenovirus prolongs survival in a human pancreatic cancer xenograft model. Chu, QD., Sun, G., Pope, M., et al.[2021]

The newly developed infectivity-enhanced COX-2 promoter-based conditionally replicative adenoviruses (CRAds) effectively target and kill pancreatic cancer cells, showing a strong antitumor effect in both in vitro and in vivo models.

Systemic administration of these CRAds demonstrated minimal toxicity, with no significant adverse effects on major organs and low levels of viral RNA detected in the liver, indicating a safe therapeutic profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infectivity enhanced, cyclooxygenase-2 promoter-based conditionally replicative adenovirus for pancreatic cancer. Yamamoto, M., Davydova, J., Wang, M., et al.[2019]

The novel oncolytic adenovirus AV25CDC, driven by the CDC25B promoter, showed a strong ability to kill pancreatic cancer cells in vitro and significantly reduced tumor size by 70% to 80% in vivo when combined with gemcitabine in mouse models.

Treatment with AV25CDC not only effectively reduced tumor growth but also normalized liver toxicity markers and significantly lowered CA19.9 serum levels, indicating a potential for safe and effective chemovirotherapy in pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Novel CDC25B Promoter-Based Oncolytic Adenovirus Inhibited Growth of Orthotopic Human Pancreatic Tumors in Different Preclinical Models. Weber, HL., Gidekel, M., Werbajh, S., et al.[2022]

The newly developed Ad-SGE-REIC vector significantly increased the expression of the REIC/Dkk-3 tumor suppressor gene in pancreatic cancer cells compared to the conventional Ad-CAG-REIC vector.

Ad-SGE-REIC not only reduced cell viability and induced apoptosis in pancreatic cancer cell lines but also demonstrated superior tumor growth inhibition in a mouse model, suggesting it could be a more effective treatment option for pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel REIC/Dkk-3-encoding adenoviral vector as a promising therapeutic agent for pancreatic cancer. Sawahara, H., Shiraha, H., Uchida, D., et al.[2020]

The study developed a novel adenovirus (Ad5MK) that selectively targets pancreatic cancer cells expressing midkine, showing significant anti-tumor effects in both cell lines and mouse models, particularly in those with high midkine expression.

Ad5MK demonstrated greater cytotoxicity against midkine-expressing pancreatic cancer cells compared to midkine-negative cells, suggesting its potential as a targeted gene therapy for pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Midkine promoter-based conditionally replicative adenovirus therapy for midkine-expressing human pancreatic cancer. Toyoda, E., Doi, R., Kami, K., et al.[2021]

In murine models of pancreatic adenocarcinoma, treatment with an adenovirus vector encoding soluble Flk1 (Flk1-Fc) resulted in significantly reduced tumor volumes, with 75% smaller tumors in murine models and 78% smaller tumors in human models compared to control treatments after 6 weeks.

Mice treated with Flk1-Fc showed longer survival rates and less liver tumor replacement, indicating that this antiangiogenic gene therapy could be a promising approach for improving outcomes in pancreatic cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adenovirus-mediated delivery of a soluble form of the VEGF receptor Flk1 delays the growth of murine and human pancreatic adenocarcinoma in mice. Tseng, JF., Farnebo, FA., Kisker, O., et al.[2009]

Pancreatic ductal adenocarcinoma (PDAC) has a very low 5-year survival rate and is characterized by an aggressive nature and resistance to standard treatments like gemcitabine, highlighting the urgent need for new therapies.

Oncolytic adenoviruses show promise as a novel treatment option, demonstrating safety in clinical trials and potential efficacy when combined with existing chemotherapies, as they can activate anti-tumor immune responses and penetrate the tumor's protective stroma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in oncolytic adenovirus therapy for pancreatic cancer. Nattress, CB., Halldén, G.[2022]

Targeting pancreatic tumors through intraductal injection of adenoviruses significantly improves viral distribution and tumor targeting compared to intravenous delivery, as shown in two mouse models of pancreatic cancer.

The combination of intraductal adenovirus delivery with ganciclovir treatment resulted in substantial tumor regression and increased survival rates in mice with pancreatic xenografts, demonstrating a promising approach for localized pancreatic cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraductal delivery of adenoviruses targets pancreatic tumors in transgenic Ela-myc mice and orthotopic xenografts. José, A., Sobrevals, L., Miguel Camacho-Sánchez, J., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06693986

NCT06693986 | Adenovirus (RGDCRAdCOX2F) This is a single center, Phase I dose finding study of a single direct tumor injection of an RGD modified conditionally replicative adenovirus (RGDCRAdcox2F)

2. withpower.com withpower.com/trial/adenovirus-vector-for-pancreatic-cancer-25c2f

Adenovirus Vector for Pancreatic Cancer The treatment RGDCRAdCOX2F is unique because it uses a genetically modified adenovirus to specifically target and destroy pancreatic cancer cells while sparing ...

3. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/555818

Adenovirus (RGDCRAdCOX2F) - Carebox Connect The study is designed to determine the MTD of RGDCRAdCOX2F that corresponds to the maximum desired toxicity of ≤ 20%. Read more.

4. studyfinder.umn.edu studyfinder.umn.edu/studies/31825

A Phase I Study of a Tropism Modified Conditionally ... Description: This is an early study of a new drug, RGDCRAdCOX2F, as a single tumor injection in persons with adenocarcinoma of the pancreas.

5. gastrojournal.org gastrojournal.org/article/S0016-5085(03)01196-X/fulltext

Infectivity enhanced, cyclooxygenase-2 promoter-based ... In pancreatic cancer cells, CRAds with the left-to-right direction E1 expression cassettes (CRAdcox2F and RGDCRAdcox2F) exhibited a cytocidal effect in 4 of 4 ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06693986

NCT06693986 | Adenovirus (RGDCRAdCOX2F) The study is designed to determine the MTD of RGDCRAdCOX2F that corresponds to the maximum desired toxicity of ≤ 20%. Official Title. A Phase I Study of a ...