Fluorescence Image Guided Surgery Followed by Intraoperative Photodynamic Therapy for Improving Local Tumor Control in Patients With Locally Advanced or Recurrent Colorectal Cancer

NCT06307548 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: I-3670923NCI-2024-01256UL1TR001412
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial studies the side effects and how well fluorescence image guided surgery followed by intraoperative photodynamic therapy for improving local tumor control in patients with colorectal cancer that has spread to nearby tissue or lymph nodes (locally advanced) or that has come back after a period of improvement (recurrent). Fluorescence image guided surgery uses a drug named aminolevulinic acid hydrochloride. Aminolevulinic acid hydrochloride is a photosensitizing agent, meaning that is activated by light and, is converted to another drug in cancer cells more than in normal cells. The converted drug emits fluorescence red light when activated with low power blue light. It is used to assist the surgeon to see cancer cells and small cancerous tissue that may have been missed during routine surgery. In addition to emitting fluorescence light, the converted drug in the cancer cells and tissue can be activated with red laser light to kill cancer cells. This procedure is called photodynamic therapy (PDT). Performing fluorescence image guided surgery followed by intraoperative photodynamic therapy after the surgical removal of the colorectal tumor before the surgical site will be closed may be effective and improve outcomes in patients with locally advanced or recurrent colorectal cancer.

Conditions

Recurrent Colorectal Carcinoma; Stage III Colorectal Cancer; Locally Advanced Colorectal Carcinoma

Outcome Measures

Primary Outcomes (4)

• Accuracy of the fluorescence imaging (Phase I)

  Will be determined by histopathology by examining the number of true positive fluorescence cases out of the total positive fluorescence biopsies collected in the study. This will be determined by reviewing the pathology reports. The proportion of surgical cases exhibiting a positive fluorescence signal by utilizing a simple proportion along with a 95% confidence interval.

  Up to 3 years

• Incidence of adverse events (Phase I)

  Will be measured by recording Gleolan administration and intraoperative photodynamic therapy (PDT) treatment related adverse events that are ≥ grade 3 with attribution of 'probable', or 'definite', according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0, that do not resolve within 7 days.

  Up to 30 days post-therapy

• Evidence of disease (Phase II)

  Will be assessed by standard-of-care computed tomography (CT) and/or magnetic resonance imaging (MRI). The recurrence proportion and exact 95% confidence interval will be calculated.

  At 12 weeks post treatment

• Changes in carcinoembryonic antigen (CEA) and circulating tumor deoxyribonucleic acid (ctDNA) (Phase II)

  Will be evaluated by collecting peripheral blood samples. The mean and a 95% confidence interval will be calculated around the mean change from baseline.

  Within 4 weeks prior to surgical/PDT intervention and 4-6 weeks after treatment

Secondary Outcomes (6)

• Changes in CEA and ctDNA (Phase I)

  At 4 weeks prior to surgical/PDT intervention and 4-6 weeks after treatment

• Rate of recurrence (Phase I)

  At approximately 3 months post treatment, and during long term followup will be part (every 3 to 6 months up to 3 years)

• Rate of local recurrence (Phase II)

  Within 3 years post treatment during standard of care follow ups

• Disease free survival (Phase II)

  Up to 3 years after treatment

• Correlation between disease free survival and changes in levels of CEA (Phase II)

  At 4-6 weeks after treatment

Study Arms (1)

Treatment (aminolevulinic, fluorescence-guided surgery, PDT)

EXPERIMENTAL

Patients receive aminolevulinic acid PO 2 to 4 hours prior to SOC surgery. Patients then undergo image-guided fluorescence 5-10 minutes post surgery, and intraoperative PDT 15-45 minutes post surgery. Patients also undergo CT or MRI during screening and on follow up. Patients also undergo blood sample collection throughout the trial.

Drug: Aminolevulinic Acid; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Fluorescence-Guided Surgery; Procedure: Magnetic Resonance Imaging; Drug: Photodynamic Therapy; Procedure: Surgical Procedure

Interventions

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, CT, CT Scan, tomography

Treatment (aminolevulinic, fluorescence-guided surgery, PDT)

Fluorescence-Guided Surgery PROCEDURE

Undergo fluorescence-guided surgery

Also known as: Fluorescence-Guided Surgical Procedure

Treatment (aminolevulinic, fluorescence-guided surgery, PDT)

Surgical Procedure PROCEDURE

Undergo surgery

Also known as: Operation, Surgery, Surgery Type, Surgery, NOS, Surgical, Surgical Intervention, Surgical Interventions, Surgical Procedures, Type of Surgery

Treatment (aminolevulinic, fluorescence-guided surgery, PDT)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (aminolevulinic, fluorescence-guided surgery, PDT)

Photodynamic Therapy DRUG

Undergo PDT

Also known as: PDT, Photoradiation Therapy

Treatment (aminolevulinic, fluorescence-guided surgery, PDT)

Aminolevulinic Acid DRUG

Given PO

Also known as: 5-ALA, 5-Aminolaevulinic Acid, 5-Aminolevulinic Acid, Amino-Levulinic Acid, Delta Aminolevulinic Acid, Delta-Aminolevulinic Acid

Treatment (aminolevulinic, fluorescence-guided surgery, PDT)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (aminolevulinic, fluorescence-guided surgery, PDT)

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years of age
• Patients with locally advanced or recurrent colorectal cancer undergoing surgery
• Amenable to diagnostic CT and MR imaging
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 3
• Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
• Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure

You may not qualify if:

• Pregnant or nursing female participants
• Any condition which in the Investigator's opinion deems the participant an unsuitable candidate to receive the fluorescence-guided surgery with intraoperative PDT
• Patients with porphyria, or with known hypersensitivity to porphyrins or porphyrin-like compounds
• Patients who are not cleared to undergo surgery
• Patients with any acute hepatitis or chronic liver dysfunction with baseline elevated liver function tests (i.e. Aspartate transaminase (AST)/alanine transaminase (ALT) ≥ 2.5 x upper limit of normal \[ULN\]) will be excluded from the study
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Patients unwilling or unable to follow protocol requirements
• Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug and/or procedure

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead
• National Center for Advancing Translational Sciences (NCATS): collaborator

Study Sites (1)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Aminolevulinic Acid; Specimen Handling; Magnetic Resonance Spectroscopy; Photochemotherapy; 1-phenyl-3,3-dimethyltriazene; Phototherapy; Surgical Procedures, Operative

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)

Levulinic Acids; Keto Acids; Carboxylic Acids; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical; Combined Modality Therapy; Therapeutics; Drug Therapy

Study Officials

• Anthony S Dakwar

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2024
• First Posted: March 13, 2024
• Study Start: July 30, 2024
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: May 6, 2026

Record last verified: 2026-05

Locations

US (1)