Trial of ProAgio in Advanced/Metastatic Colorectal Cancer

NCT06867822 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: IRB-300014432 (UAB2479)T2024-020
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label Phase I/Ib dose-escalation, dose-expansion clinical trial of the safety, pharmacokinetics and clinical activity of ProAgio combined with 5-fluorouracil, irinotecan (FOLFIRI) and bevacizumab for untreated advanced/metastatic CRC. The study will use an Accelerated titration BOIN design in Phase I to determine the recommended RP2D of ProAgio with FOLFIRI + bevacizumab. The trial will estimate the RP2D of ProAgio when combined with FOLFIRI + bevacizumab, starting from 2 dose levels lower than the estimated RP2D of ProAgio alone. Accelerated titration BOIN design will enroll patients with the 4 combination dose levels. Subjects will be selected based on following criteria: previously untreated advanced/metastatic CRC, ECOG performance status (0-1), and adequate organ functions. Subjects with recent surgeries, history of recent thromboembolic events or significant cardiovascular disease will be excluded. Once the MTD and RP2D of ProAgio with FOLFIRI have been identified, an expansion cohort of 12 subjects with advanced/metastatic CRC will begin. The purpose of the expansion cohort is to confirm the safety of the regimen and provide preliminary data on the activity of ProAgio + FOLFIRI + bevacizumab.

Conditions

Advanced Colorectal Cancer; Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Change in NCI CTCAE scale version 5.0

  National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE.

  Baseline, up to 18 months

Secondary Outcomes (4)

• Evaluate the pharmacokinetics of ProAgio

  Baseline, up to 10 months

• Assessment of anti-tumor activity by measuring objective response rate (ORR)

  up to 12 weeks

• Progression free survival (PFS) - duration of time from start of treatment to time of progression or death, whichever occurs first.

  up to 18 months

• Overall survival (OS) - the length of time from start of treatment until death from any cause.

  up to 18 months

Study Arms (2)

Phase I: dose escalation ProAgio + FOLFIRI + bevacizumab dose levels tested for RP2D

EXPERIMENTAL

Dose level ProAgio mg/Kg FOLFIRI + bevacizumab 1. MTD-2 (6.4\*) FOLFIRI + bevacizumab 2. MTD-1 (10.7) FOLFIRI + bevacizumab 3. MTD (12.5) FOLFIRI + bevacizumab 4. MTD+1 (16\*) FOLFIRI + bevacizumab ProAgio will be administered via IV over 60 minutes on Day 1, 8, 15, and 21 every 4-week cycle. Bevacizumab 5 mg/kg, Irinotecan 180 mg/m2, 5-Flurouracil infusion 2400 mg/m2 will be administered via IV on Day 1, and 15 every 4-week cycle. The study will use an Accelerated titration BOIN design in Phase I to determine the recommended RP2D of ProAgio with FOLFIRI + bevacizumab. The trial will estimate the RP2D of ProAgio when combined with FOLFIRI + bevacizumab, starting from 2 dose levels lower than the estimated RP2D of ProAgio alone. Accelerated titration BOIN design will enroll patients with the 4 combination dose levels listed above, maximum of 15 subjects.

Drug: ProAgio; Drug: FOLFIRI; Drug: Bevacizumab

Phase Ib: dose expansion ProAgio + FOLFIRI + bevacizumab

EXPERIMENTAL

Once the MTD and RP2D of ProAgio with FOLFIRI have been identified, an expansion cohort of 12 subjects with advanced/metastatic CRC will begin. The purpose of the expansion cohort is to confirm the safety of the regimen and provide preliminary data on the activity of ProAgio + FOLFIRI + bevacizumab.

Drug: ProAgio; Drug: FOLFIRI; Drug: Bevacizumab

Interventions

ProAgio DRUG

ProAgio is a pegylated protein with a single pegylated site. The 12,131 Dalton protein is produced in E. coli and is composed of 105 amino acids with no disulfide bonds. The structure of the polyethylene glycol moiety is Methoxy PEG maleimide 30000.

Also known as: ACT50

Phase I: dose escalation ProAgio + FOLFIRI + bevacizumab dose levels tested for RP2D; Phase Ib: dose expansion ProAgio + FOLFIRI + bevacizumab

FOLFIRI DRUG

FOLFIRI is a combination of three drugs: (leucovorian, fluorouracil, and irinotecan) used to treat advanced metastatic colorectal cancer. FOLFIRI is commercially available will be administered using standard dosing regimen as per institutional guidelines.

Also known as: Irinatecan, 5-fluorouracil, folinic acid (leucovorin)

Phase I: dose escalation ProAgio + FOLFIRI + bevacizumab dose levels tested for RP2D; Phase Ib: dose expansion ProAgio + FOLFIRI + bevacizumab

Bevacizumab DRUG

Bevacizumab is a recombinant humanized monoclonal antibody that blocks angiogenesis by inhibiting vascular endothelial growth factor A (VEGF-A). Bevacizumab is commercially available and will be administered using standard dosing regimen as per institutional guidelines.

Also known as: Avastin

Phase I: dose escalation ProAgio + FOLFIRI + bevacizumab dose levels tested for RP2D; Phase Ib: dose expansion ProAgio + FOLFIRI + bevacizumab

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be ≥18 years of age at the time of consent.
• Histologic or cytologic diagnosis of colorectal adenocarcinoma (CRC)
• Patients with advanced or metastatic CRC
• Performance status, ECOG: 0, 1
• For dose escalation phase: patients with CRC where FOLFIRI+ bevacizumab is considered appropriate standard therapy (previously treated with FOLFOX based regimen in advanced/metastatic CRC is allowed). For dose expansion phase: patients must not have received 5FU-based therapy previously for metastatic disease. Patients who received FOLFOX/CAPOX regimens in the neoadjuvant/adjuvant setting are allowed if recurrence free survival is at least 1 year or longer since completion of adjuvant therapy.
• Presence of a metastatic lesion that can be safely biopsied for correlative assays (Only for FOUR patients enrolling on the dose expansion phase).
• Patient must meet the following laboratory values at the screening visit:
• Absolute Neutrophil Count ≥1.5 x 109/L
• Platelets ≥100 x 109/L
• Hemoglobin (Hgb) ≥9 g/dL
• Creatinine Clearance ≥60 mL/min using Cockcroft-Gault formula
• Total bilirubin ≤1.5 x ULN
• Aspartate transaminase (AST) ≤2.5 x ULN, except for subjects with liver metastasis, who may only be included if AST ≤5.0 x ULN
• Alanine transaminase (ALT) ≤2.5 x ULN, except for subjects with liver metastasis, who may only be included if ALT ≤5.0 x ULN
• Urine dipstick reading for proteinuria \< 2+. Participants having ≥ 2+ proteinuria on urine dipstick testing at baseline will undergo a 24-hour urine collection for quantitative assessment of proteinuria and must demonstrate \< 1 g of protein in 24 hours. Participants with urine protein ≥ 1 g per 24 hours will be ineligible

You may not qualify if:

• Prior exposure to FOLFIRI chemotherapy
• Clinically significant peripheral neuropathy (\>=Grade 3 per CTCAE 5.0)
• Any untreated central nervous system (CNS) lesion. However, subjects are eligible if: a) all known CNS lesions have been treated with radiotherapy or surgery and b) patient remained without evidence of CNS disease progression ≥4 weeks after treatment.
• Allogenic bone marrow or solid organ transplant
• Known history or current interstitial lung disease or non-infectious pneumonitis
• Prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen, per treating physician discretion.
• Known additional malignancy that is progressing or requires active treatment, with the exception of patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or antitumor assessment of the investigational regimen.
• Subject has known dihydropyrimidine dehydrogenase (DPD) deficiency. (NOTE: DPD testing is not mandatory as part of the trial and can be performed at the discretion of treating provider per local requirements)
• Subject has known immediate or delayed hypersensitivity, intolerance or contraindication to any component of study treatment
• Infection with human immunodeficiency virus (HIV)-1 or HIV-2. (Exception:
• Participants with well-controlled HIV \[ie, CD4 \> 350/mm3 and undetectable viral load\] are eligible.)
• Active hepatitis, including the following:
• Acute or chronic hepatitis B (Exception: Participants who are hepatitis B surface antigen \[HbsAg\] positive are eligible if they have hepatitis B virus (HBV) DNA less than 500 IU/mL or 2,500 copies/mL). Note: Participants with detectable HbsAg or detectable HBV DNA should be managed per institutional or local standards. Participants beginning antiviral agents at screening should be treated for \> 2 weeks prior to expected date of C1D1.
• Infection with hepatitis C (Exceptions: \[i\] Participants who have no history of curative viral treatment and are documented to be viral load negative are eligible; \[ii\] Participants who have completed curative viral therapy ≥ 12 weeks prior to expected date of C1D1, and viral load is negative are eligible.)
• Severe chronic or active infections requiring systemic parenteral antibacterial, antifungal or antiviral therapy; or any other potentially life-threatening viral or bacterial infection (participants on oral antibiotics must complete the planned course of treatment prior to expected date of C1D1).

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• The V Foundation: collaborator

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

IFL protocol; Fluorouracil; Leucovorin; Bevacizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Midun Malla, MD

CONTACT

(205) 934-2992; midhunmalla@uabmc.edu

Margaret Thomas, MPH

CONTACT

margaretannthomas@uabmc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: March 4, 2025
• First Posted: March 10, 2025
• Study Start: July 17, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2028
• Last Updated: August 24, 2025

Record last verified: 2025-08

Locations

US (1)