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Advanced Colorectal CancerPhase 1NCT06867822

Trial of ProAgio in Advanced/Metastatic Colorectal Cancer

A Phase 1 study testing ProAgio, FOLFIRI and Bevacizumab in people with Advanced Colorectal Cancer and Metastatic Colorectal Cancer, run by University of Alabama at Birmingham at 1 site in United States.

Suspended

Paused. Enrolment is on hold for now and may resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 19 years and older
What is being tested?
ProAgio, FOLFIRI and Bevacizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
27 participants
Where
1 siteUnited States
Study dates
17 Jul 2025to Jul 2028
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 19 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
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  • 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
  • Blood pressure <=160/100 mm Hg
  • Presence of measurable disease by RECIST 1.1 criteria within 28 days prior to the first dose of study treatment.
  • Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0- 1 (Appendix A-Performance Status Criteria).
  • Normal ECG defined as the following: QTcF at screening <450 ms (male subjects), <460 ms (female subjects)
  • Before enrollment, a woman must be either:
  • Not of childbearing potential: postmenopausal (>45 years of age with amenorrhea for at least 12 months or any age with amenorrhea for at least 6 months and a serum follicle stimulating hormone (FSH) level >40 IU/mL); permanently sterilized (eg, tubal occlusion, hysterectomy, bilateral salpingectomy); or otherwise be incapable of pregnancy.
  • Of childbearing potential and practicing (during the study and for 6 months after receiving the last dose of study agent for women and 3 months after receiving the last dose of study agent for men)) a highly effective method of birth control consistent with local regulations regarding the use of birth control methods for subjects participating in clinical studies: e.g., established use of oral, injected or implanted hormonal methods of contraception; placement of an intrauterine device (IUD) or intrauterine system (IUS); barrier methods; true abstinence (when this is in line with the preferred and usual lifestyle of the subject).
  • Note: If the childbearing potential changes after start of the study (eg, woman who is not heterosexually active becomes active) a woman must begin a highly effective method of birth control, as described above.
  • A woman of childbearing potential must have a negative serum (β-human chorionic gonadotropin [β-hCG]) or urine pregnancy test at screening.
  • During the study and for 6 months after receiving the last dose of study agent, a woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction.
  • A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control e.g., either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, and all men must also not donate sperm during the study and for 3 months after receiving the last dose of study drug.
  • Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written informed consent and privacy language as per HIPAA must be obtained from the subject or legally authorized representative (if applicable) prior to any study- related procedures
  • Sign an informed consent document indicating that they understand the purpose of and procedures required for the study, are willing to participate in the study, and are willing and able to adhere to the prohibitions and restrictions specified in this protocol. Informed consent must be obtained before performing any study specific procedures.
  • As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study
  • Subject agrees not to participate in another interventional study while receiving study drug in present study

Who cannot join

  • 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.
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  • 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).
  • Received an investigational drug (including investigational vaccines) or used an invasive investigational medical device within 14 days or 5 half-lives before enrollment or is currently enrolled in the treatment stage of an investigational study.
  • A woman who is pregnant or breast-feeding, or a woman who is planning to become pregnant or a man who plans to father a child while enrolled in this study or within 150 days after the last dose of study agent.
  • Subject has had a major surgical procedure ≤ 28 days prior to randomization. Subject without complete recovery from a major surgical procedure ≤ 14 days prior to randomization
  • Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
  • Subject has psychiatric illness or social situations such as incarceration that would preclude study compliance, per investigator judgment
  • Patients with a history of perforation, fistula, life-threatening gastrointestinal bleeding, proteinuria (>1 gm/24 hours), wound healing issues
  • Subject has significant cardiovascular disease, including any of the following:
  • Congestive heart failure (defined as New York Heart Association [NYHA] Class III or IV), myocardial infarction, unstable angina, coronary angioplasty, coronary stenting, coronary artery bypass graft, cerebrovascular accident (CVA), or hypertensive crisis within 6 months prior to randomization;
  • History of clinically significant ventricular arrhythmias (i.e., sustained ventricular tachycardia, ventricular fibrillation, or Torsades de Pointes);
  • History or family history of congenital long QT syndrome
  • Cardiac arrhythmias requiring anti-arrhythmic medications (Subjects with rate controlled atrial fibrillation for > 1 month prior to randomization are eligible.)
  • Deep venous thrombosis/pulmonary embolism (within last 6 months) unless adequately treated with therapeutic anticoagulation.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294

Other trials in United States

About this study

Official title: A Phase I/Ib Trial of ProAgio, an Anti-avb3 Integrin Cytotoxin, in Combination With 5-fluorouracil , Irinotecan and Bevacizumab for Advanced/Metastatic Colorectal Cancer (ProAgio in CRC)

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.

Being tested
ProAgio, FOLFIRI, Bevacizumab
Medical subject headings
Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ProAgioDrug

    Also called ACT50

    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.

  • FOLFIRIDrug

    Also called Irinatecan, 5-fluorouracil, folinic acid (leucovorin)

    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.

  • BevacizumabDrug

    Also called Avastin

    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.

Study groups in NCT06867822
Study groupRoleWhat they receive
Phase I: dose escalation ProAgio + FOLFIRI + bevacizumab dose levels tested for RP2DExperimentalDose 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.
Receives: Drug: ProAgio; Drug: FOLFIRI; Drug: Bevacizumab
Phase Ib: dose expansion ProAgio + FOLFIRI + bevacizumabExperimentalOnce 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.
Receives: Drug: ProAgio; Drug: FOLFIRI; Drug: Bevacizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline, up to 18 months

Secondary outcomes (4)

  1. Evaluate the pharmacokinetics of ProAgio

    Assessed by measurement of serum levels of ProAgio over time following IV infusion.

    Measured: Baseline, up to 10 months

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

    The proportion of participants with partial response or complete response. RECIST 1.1 will be used to assess ORR.

    Measured: up to 12 weeks

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

    Determined from date of 1st dose of study drug to disease progression and/or death from any cause.

    Measured: up to 18 months

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

    Determined from date of 1st dose of study drug to death from any cause.

    Measured: up to 18 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Mar 2025
  2. Study start17 Jul 2025
  3. Primary completionJul 2027 (estimated)
  4. Study completionJul 2028 (estimated)

Why it stopped: temporary suspended

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
27 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06867822
Sponsor's protocol ID
IRB-300014432 (UAB2479)
Other IDs
T2024-020
Status last verified
Sep 2026
First submitted
4 Mar 2025
Last updated
2 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ProAgio, FOLFIRI and Bevacizumab in people with Advanced Colorectal Cancer and Metastatic Colorectal Cancer, run by University of Alabama at Birmingham at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 30 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: paused, as of the sponsor's last update on 2 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in NCI CTCAE scale version 5.0 (time frame: Baseline, up to 18 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06867822.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2026.

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