ProAgio + Chemotherapy for Pancreatic Cancer

Overseen By Damon R Michaels

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: ProDa BioTech, LLC

Must be taking: Gemcitabine, Nab paclitaxel

Must not be taking: Hematopoietic growth factors

Disqualifiers: Peripheral neuropathy, CNS lesions, others

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

Compensation: Varies

Number of Visits: 8

46 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a new treatment called ProAgio, combined with chemotherapy drugs, to combat metastatic pancreatic cancer. The trial includes different groups to test various drug combinations. Participants must have a diagnosis of stage IV pancreatic cancer and must not have received gemcitabine and nab-paclitaxel treatment. The focus is to determine if this new combination can better manage the cancer. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive it.

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, certain medications like hematopoietic growth factors must be stopped 2 weeks before starting the trial, unless they were started earlier and are stable.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that ProAgio is generally safe for people. Studies have found it to be well-tolerated at various doses. For example, one study demonstrated a strong safety record for ProAgio, with very few serious side effects. A rare case involved high blood sugar in a participant with diabetes who required insulin. Overall, ProAgio appears to be a promising treatment with manageable safety concerns. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for pancreatic cancer, which typically involve chemotherapy drugs like gemcitabine and nab-paclitaxel, the investigational drug ProAgio offers a novel approach. ProAgio is unique because it targets a specific protein involved in the tumor's microenvironment, potentially disrupting cancer growth and spread more effectively. Researchers are particularly excited because ProAgio, when combined with existing chemotherapy agents, could enhance their effectiveness, offering new hope for better treatment outcomes in pancreatic cancer.

What evidence suggests that this trial's treatments could be effective for pancreatic cancer?

This trial will evaluate ProAgio in combination with chemotherapy for pancreatic cancer. Studies have shown that ProAgio yields promising results in treating this disease. In animal studies, ProAgio extended the lifespan of mice with pancreatic cancer. In humans, five participants with pancreatic cancer who took ProAgio experienced stable disease, meaning their cancer did not worsen. ProAgio also demonstrated tumor-fighting capabilities in several pancreatic cancer tests. It enhanced the effectiveness of gemcitabine, a common chemotherapy drug. This evidence suggests ProAgio might be a useful treatment for pancreatic cancer. Participants in this trial may receive ProAgio alone or in combination with gemcitabine and nab-paclitaxel, depending on the treatment arm. ^{1 2 3 6 7}

Who Is on the Research Team?

Mehmet Akce, MD

Principal Investigator

The University of Alabama at Birmingham

Are You a Good Fit for This Trial?

This trial is for adults with stage IV pancreatic ductal adenocarcinoma who haven't been treated before. They must have good liver, kidney, and blood health as shown by specific medical tests. Participants need a tumor that can be safely biopsied and should not have had certain other cancer treatments recently.

Inclusion Criteria

Written informed consent must be obtained prior to any screening procedures

Normal ECG defined as specific QTcF values

My diagnosis is stage IV pancreatic cancer.

Exclusion Criteria

I have no other cancer besides the one being treated in this study, with some exceptions.

I have a brain lesion that hasn't been treated, but it meets certain conditions.

Received an investigational drug or used an invasive investigational medical device within a defined timeframe

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

ProAgio combined with gemcitabine and nab paclitaxel is administered to study participants by intravenous injections on days 1, 8, 15, 22 every 4-week Cycle to determine the recommended RP2D.

16 weeks

4 visits per cycle (in-person)

Dose Expansion

An expansion cohort of 12 subjects will confirm the safety of the regimen and provide preliminary data on the activity of both ProAgio monotherapy and ProAgio + GnP.

16 weeks

4 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with response evaluated every 2 months using RECIST criteria.

8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ProAgio

Trial Overview The trial is testing different doses of ProAgio combined with chemotherapy drugs gemcitabine and nab paclitaxel in patients. It's to see how safe it is, how the body processes it, and if it works against metastatic pancreatic cancer.

How Is the Trial Designed?

Group I: Standard Arm Experimental Treatment 2 Interventions

In cycle 1 of dose expansion phase of the study, half of patients (n=6) will be administered ProAgio only on day 1, 8, 15, 22 every 4-week Cycle, and half of patients (n=6) will be administered gemcitabine and nab paclitaxel are administered day 1, 8, 15 every 4-week cycle. In the atezolizumab containing cohort atezolizumab will be administered day 1 of cycle 1, and then will be repeated every 3 weeks. Other Names: ACT50, G-nP: Gemcitabine and nab-Paclitaxel, atezolizumab

Group II: Dose Escalation Experimental Treatment 2 Interventions

ProAgio Dose Levels (DL) 1,2,3,4 ProAgio combined with gemcitabine, and nab paclitaxel is administered to study participants by intravenous injections on days 1, 8, 15, 21 every 4-week Cycle, gemcitabine and nab paclitaxel on day 1, 8, 15 every 4-week cycle during the study. Other Names: ACT50, G-nP: Gemcitabine, nab-Paclitaxel

Who Is Running the Clinical Trial?

ProDa BioTech, LLC

Lead Sponsor

Trials

3

Recruited

140+

University of Alabama at Birmingham

Collaborator

Trials

1,677

Recruited

2,458,000+

Georgia State University

Collaborator

Trials

71

Recruited

33,600+

Published Research Related to This Trial

Chemotherapy for advanced pancreatic cancer shows low overall activity but can provide a slight survival benefit and improve quality of life for some patients, as indicated by a systematic review of eight small randomized trials.

While gemcitabine is an approved treatment in some countries, there is no standard chemotherapy regimen established, and conclusive evidence for the use of adjuvant chemotherapy remains lacking due to the small number of patients in relevant trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy in the treatment of cancer of the pancreas. Glimelius, B.[2022]

In a phase 3 trial involving 368 patients with completely resected pancreatic cancer, adjuvant treatment with gemcitabine for 6 months significantly improved both disease-free survival (13.4 months vs. 6.7 months) and overall survival (20.7% vs. 10.4% at 5 years) compared to observation alone.

The study demonstrated that gemcitabine not only prolongs the time before cancer recurrence but also enhances overall survival rates, providing strong evidence for its use in patients after surgical removal of pancreatic tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. Oettle, H., Neuhaus, P., Hochhaus, A., et al.[2022]

Neoadjuvant chemotherapy, given before surgery, is safe and effective for patients with resectable pancreatic cancer, potentially improving their nutritional status and leading to a median survival of 26.5 months, as shown in a recent phase II trial.

The NEOPAC phase III trial will compare the efficacy of neoadjuvant chemotherapy followed by surgery against surgery followed by adjuvant chemotherapy, with a primary focus on progression-free survival in 310 patients, aiming to provide valuable insights into treatment outcomes for pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant gemcitabine versus NEOadjuvant gemcitabine/oxaliplatin plus adjuvant gemcitabine in resectable pancreatic cancer: a randomized multicenter phase III study (NEOPAC study). Heinrich, S., Pestalozzi, B., Lesurtel, M., et al.[2022]

In a study of 49 patients with locally advanced or metastatic pancreatic ductal adenocarcinoma (PDA) treated with FOLFIRINOX, the overall response rate was 41%, with a median overall survival of 18.4 months for locally advanced cases and 12.2 months for metastatic cases, indicating significant efficacy of the treatment.

The treatment was associated with notable toxicities, including neutropenia (29%) and fatigue (18%), but careful patient selection and monitoring of biomarkers like CA 19-9 can help improve outcomes and manage risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FOLFIRINOX for locally advanced or metastatic pancreatic ductal adenocarcinoma: the Royal Marsden experience. Moorcraft, SY., Khan, K., Peckitt, C., et al.[2022]

Pancreatic adenocarcinoma is often diagnosed at advanced stages, with 80% of cases being inoperable or metastatic, leading to a low 1-year survival rate of 20-50% depending on treatment and patient condition.

Adjuvant chemotherapy after surgery can significantly improve survival rates, potentially doubling the chances of survival, while new evidence-based treatment options are being integrated into clinical practice to enhance patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Current standards in the treatment of pancreatic cancer]. Pelzer, U., Riess, H.[2015]

Citations

1. 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.

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

Phase I study of ProAgio, an αvβ3 integrin cytotoxin, in ... Five participants with pancreatic cancer receiving weekly dosing of ProAgio had stable disease, 2 of which had interval stabilization in CA 19-9 ...

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 What is the purpose of this trial? This trial tests a new drug called ProAgio for safety and effectiveness in patients with advanced pancreatic cancer.

5. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05085548/proagio-in-previously-treated-advanced-pancreatic-cancer-and-other-solid-tumor-malignancies

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. aacrjournals.org aacrjournals.org/mct/article/22/12_Supplement/B047/730522/Abstract-B047-Phase-I-trial-of-v-3-integrin

Abstract B047: Phase I trial of αvβ3 integrin cytotoxin ProAgio ... A serious adverse event of grade 3 hyperglycemia was observed in 1 participant with insulin-dependent diabetes within 24 hours of ProAgio ...

7. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/446215

ProAgio in Pancreatic Ductal Adenocarcinoma (PDAC) This is an open-label Phase I/Ib dose-escalation, dose-expansion clinical trial of the safety, pharmacokinetics and clinical activity of ProAgio combined ...