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Trial of ProAgio in Advanced/Metastatic Colorectal Cancer

ConditionsAdvanced Colorectal CancerMetastatic Colorectal Cancer
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age19+
SponsorUniversity of Alabama at Birmingham

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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

Trial design

Design model

Single group

Treatments tested in this trial

  • 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.

  • 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.

  • 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.

Treatment groups

27 Participants
are divided into 2 treatment groups
Group A: Phase I: dose escalation ProAgio + FOLFIRI + bevacizumab dose levels tested for RP2DExperimental treatment 3 interventions
Group B: Phase Ib: dose expansion ProAgio + FOLFIRI + bevacizumabExperimental treatment 3 interventions

Trial outcomes

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.

Time frame
Baseline, up to 18 months

Secondary outcomes

1

Evaluate the pharmacokinetics of ProAgio

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

Time frame
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.

Time frame
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.

Time frame
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.

Time frame
up to 18 months

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University of Alabama at Birmingham

Lead sponsor

The V Foundation

Collaborator

Source ClinicalTrials.gov
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