ProAgio for Advanced Pancreatic Cancer

Overseen By Zhi-Ren Liu

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: ProDa BioTech, LLC

Must not be taking: Steroids, Anticonvulsants

Disqualifiers: CNS tumors, Uncontrolled diseases, Pregnancy, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety of a new treatment, ProAgio, for individuals with advanced pancreatic cancer. Participants will receive ProAgio, either alone or with another drug, to observe tumor response. The trial targets those with pancreatic cancer who have unsuccessfully tried at least one other treatment. Individuals with recurring or advanced cancer, who face daily challenges due to their condition, might be suitable candidates. The trial includes different groups, with some requiring tumor biopsies (a small tissue sample) before and after treatment. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must be more than 14 days removed from your most recent standard or experimental drug treatment for your tumor.

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

Research shows that ProAgio is undergoing its first human trials to assess safety in treating advanced cancers, such as pancreatic cancer. These studies primarily aim to determine the safest dosage of ProAgio. As a Phase 1 trial, it marks the initial step in evaluating the drug's safety for humans, so specific safety information is not yet available. By gradually increasing the dose, researchers aim to identify the optimal amount with minimal side effects. As the trial progresses, more detailed information will emerge about ProAgio's tolerability. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for advanced pancreatic cancer, which typically include chemotherapy drugs like gemcitabine and nab-paclitaxel, ProAgio offers a novel approach by specifically targeting the abnormal blood vessels that feed tumors. This new mechanism of action disrupts the tumor's blood supply, potentially starving the cancer cells and inhibiting their growth. Researchers are excited about ProAgio because it represents a fresh strategy that may enhance treatment effectiveness, especially for patients who have limited options with current therapies. This innovative approach could provide a new avenue for managing a challenging and aggressive cancer type.

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

Research has shown that ProAgio holds potential for treating pancreatic cancer, particularly in animal studies. ProAgio targets and kills cancer cells by interacting with a protein called αvβ3 integrin, commonly found on tumor cells. Early studies in mice demonstrated that it can slow tumor growth and extend survival. Additionally, ProAgio may enhance the effects of gemcitabine, a standard chemotherapy drug for pancreatic cancer. In this trial, participants in the Standard Arm will receive ProAgio at the recommended phase 2 dose (RP2D) and may choose to receive concurrent gemcitabine starting with Cycle 2. While these results are promising, they stem from early research, and further studies in humans are necessary to confirm its effectiveness. ^{1 3 4 5 6}

Who Is on the Research Team?

Anish Thomas, MBBS, MD

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

This trial is for adults over 18 with advanced solid tumors, including pancreatic cancer, who've had at least one prior treatment. They must have a tumor that can be biopsied or measurable disease and good organ function. Participants need to use contraception and cannot join if they're pregnant, have significant uncontrolled diseases, active infections, recent surgery or radiation therapy, untreated brain metastases, certain blood pressure or heart rate conditions.

Inclusion Criteria

My cancer is confirmed and cannot be cured, according to a pathology lab.

Ability of subject to understand and the willingness to sign a written informed consent document

I can take care of myself but may not be able to do heavy physical work.

Exclusion Criteria

I have been diagnosed with a primary brain tumor.

I do not have any active or uncontrolled infections.

I have not had uncontrolled bleeding in the last 28 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants will receive ProAgio in escalating doses to determine the maximum tolerated dose (MTD)

Variable, until MTD is determined

Expansion Cohort

Participants with advanced nonendocrine pancreatic adenocarcinoma will receive ProAgio at the MTD, with optional co-administration of gemcitabine

Until disease progression or unacceptable toxicity

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• ProAgio

Trial Overview The study tests the safety of different dose levels of ProAgio in patients with various advanced solid tumors. It's a first-in-human Phase I trial where participants are given escalating doses to find out how much of this new drug can be safely administered.

How Is the Trial Designed?

Group I: Standard Arm Experimental Treatment 2 Interventions

Participants will receive ProAgio at the RP2D and may elect to receive concurrent gemcitabine beginning with the start of Cycle 2.

Group II: Expansion Biopsy Arm Experimental Treatment 1 Intervention

Pre- and post-treatment tumor biopsy is optional for participants enrolled in the standard arm, but mandatory for participants enrolled in the biopsy arm.

Group III: Dose Escalation Experimental Treatment 3 Interventions

Participants will receive ProAgio in escalating doses.

Who Is Running the Clinical Trial?

ProDa BioTech, LLC

Lead Sponsor

Trials

3

Recruited

140+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 126 patients who underwent radical pancreatic surgery, those with adenocarcinoma had significantly worse survival rates compared to other types of tumors, highlighting the aggressive nature of this cancer.

Key factors affecting survival included tumor differentiation and nodal status, with a positive resection margin (R1) also linked to poorer outcomes, indicating the importance of complete tumor removal for better prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of surgery for pancreatic cancer: a 12-year review of patient outcome. Badger, SA., Brant, JL., Jones, C., et al.[2021]

The introduction of multidisciplinary team (MDT) meetings has not significantly changed the management of pancreatic body carcinoma, but there is a noted increase in the prevalence of more advanced disease at diagnosis, with 65.2% of patients diagnosed post-MDT presenting with stage IV tumors.

Chemotherapy was found to provide a significant survival benefit for patients, with a hazard ratio of 0.39, indicating that those receiving chemotherapy had a lower risk of death compared to those who did not, despite no overall increase in survival rates after the introduction of MDT meetings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carcinoma of the body of pancreas in evolution: an aggressive disease affecting younger patients? Dickinson, KJ., Gomez, D., Lowe, A., et al.[2007]

Over 80% of pancreatic cancer cases are diagnosed at an advanced stage, whether localized, locally advanced, or metastatic, leading to poor outcomes.

Despite advancements in cancer treatment and molecular analysis over the past 20 years, the mortality rate for advanced pancreatic cancer remains largely unchanged, highlighting the need for improved therapeutic strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advanced pancreatic cancer: The standard of care and new opportunities. Mohammad, AA.[2020]

Combined modality treatment for locally advanced pancreatic cancer, which includes both local and systemic therapies, shows better outcomes than using irradiation alone or just providing symptomatic treatment.

The prognosis for patients with this type of cancer remains poor, with median survival still only 3-5 months, highlighting the need for effective treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multimodality treatment of locally advanced pancreatic cancer. Wagener, DJ., de Mulder, PH., Wils, JA.[2019]

Over the past 12 years, outcomes for patients with advanced pancreatic cancer have improved significantly due to advancements in systemic therapies, including new strategies like switch maintenance and targeted agents for specific genetic variants.

While immunotherapy has not yet shown strong results in treating advanced pancreatic cancer, ongoing research into novel combinations and better patient selection may enhance its effectiveness in the future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advancements in Systemic Therapy for Pancreatic Cancer. Brown, TJ., Reiss, KA., O'Hara, MH.[2023]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.e16336

Phase I study of ProAgio, an αvβ3 integrin cytotoxin, in ... Phase I study of ProAgio, an αvβ3 integrin cytotoxin, in patients with previously treated advanced pancreatic cancer and other solid tumors.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05085548

NCT05085548 | ProAgio in Previously Treated Advanced ... It has demonstrated efficacy at treating pancreatic cancer and prolonging survival in mice. ProAgio is being developed for intravenous (IV) administration.

3. reporter.nih.gov reporter.nih.gov/search/9Fx59YKZTEWcjf0FahzQ0A/project-details/10996727

ProAgio in Pancreatic Cancer - NIH RePORTER Our preliminary data shows ProAgio has anti-tumor activity in multiple PDAC models and enhances the effect of gemcitabine. Histologic analyses showed ProAgio ...

4. withpower.com withpower.com/trial/phase-1-neoplasms-9-2021-ae124

ProAgio for Advanced Pancreatic Cancer The prognosis for patients with this type of cancer remains poor, with median survival still only 3-5 months, highlighting the need for effective treatment ...

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-00569

ProAgio in Previously Treated Advanced Pancreatic ... The study is a first-in-human, Phase I study to assess the safety of ProAgio in participants with advanced solid tumor malignancies including pancreatic cancer.

6. clinicalstudies.info.nih.gov clinicalstudies.info.nih.gov/protocoldetails.aspx?id=000194-C&&query=3

NIH Clinical Center: Search the Studies Researchers want to see if a new drug can help. Objective: To find the safest dose of ProAgio to treat advanced pancreatic and other types of cancer.