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

Image Guided Surgery Followed by Intraoperative Photodynamic Therapy for Improving Local Tumor Control in Patients With Loco-Regionally Advanced or Recurrent Colorectal Cancer Undergoing Surgery - Phase I/II

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Recurrent Colorectal Carcinoma; Locally Advanced Colorectal Carcinoma; Stage III Colorectal Cancer
• Intervention / Treatment: Procedure: Magnetic Resonance Imaging; Procedure: Computed Tomography; Procedure: Biospecimen Collection; Procedure: Surgical Procedure; Drug: Photodynamic Therapy; Drug: Aminolevulinic Acid; Procedure: Fluorescence-Guided Surgery

Detailed Description

PRIMARY OBJECTIVES:

I. To test the accuracy of image-guided fluorescence to detect residual disease. (Phase I) II. To determine the safety of intraoperative PDT after fluorescence-guided surgery in patients with loco-regionally advanced or recurrent colorectal cancer undergoing surgery. (Phase I) III. To determine the potential efficacy of intraoperative PDT (after image-guided fluorescence surgery). (Phase II)

SECONDARY OBJECTIVES:

I. To assess the potential efficacy of intraoperative PDT (after image-guided fluorescence surgery). (PHASE I) II. To assess the relationship between disease free survival and changes in levels of carcinoembryonic antigen (CEA) and circulating tumor DNA (ctDNA). (Phase II) III. To assess rate of recurrence by using standard-of-care computed tomography (CT) and/or magnetic resonance imaging (MRI). (Phase II)

OUTLINE:

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

After completion of study treatment, patients are followed up at 3 months, 24 weeks, and every 3 to 6 months for 3 years.

• Study Type: Interventional
• Enrollment (Estimated): 21
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
      • Contact: Anthony S. Dakwar; Phone Number: 716-845-5807; Email: Anthony.Dakwar@RoswellPark.org
      • Principal Investigator: Anthony S. Dakwar

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (aminolevulinic, fluorescence-guided surgery, PDT); 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.

Procedure: Magnetic Resonance Imaging; Undergo MRI; Other Names: MRI; Magnetic Resonance; Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR; MR Imaging; MRI Scan; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging; sMRI; Magnetic resonance imaging (procedure); MRIs; Structural MRI; Procedure: Computed Tomography; Undergo CT; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Procedure: Surgical Procedure; Undergo surgery; Other Names: Operation; Surgery; Surgery Type; Surgical; Surgical Intervention; Surgical Interventions; Surgical Procedures; Type of Surgery; Surgery, NOS; Drug: Photodynamic Therapy; Undergo PDT; Other Names: PDT; Photoradiation Therapy; Drug: Aminolevulinic Acid; Given PO; Other Names: 5-ALA; 5-Aminolevulinic Acid; 5-Aminolaevulinic Acid; Amino-Levulinic Acid; Delta Aminolevulinic Acid; Delta-Aminolevulinic Acid; Procedure: Fluorescence-Guided Surgery; Undergo fluorescence-guided surgery; Other Names: Fluorescence-Guided Surgical Procedure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in CEA and ctDNA (Phase I)	Will be evaluated by collecting peripheral blood samples. The mean and a 95% confidence interval will be calculated around the mean change from baseline.	At 4 weeks prior to surgical/PDT intervention and 4-6 weeks after treatment
Rate of recurrence (Phase I)	Will be evaluated with standard-of-care CT and/or MRI to detect evidence of disease. The recurrence proportion and exact 95% confidence interval will be calculated.	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)	Will be assessed by standard-of-care CT and/or MRI. The recurrence proportion and exact 95% confidence interval will be calculated.	Within 3 years post treatment during standard of care follow ups
Disease free survival (Phase II)	Will be detected via standard-of-care CT and/or MRI during the long-term follow-up that will be part of standard of care. The recurrence proportion and exact 95% confidence interval will be calculated.	Up to 3 years after treatment
Correlation between disease free survival and changes in levels of CEA (Phase II)	Monitoring of CEA levels in correlation with disease free survival	At 4-6 weeks after treatment
Correlation between disease free survival and changes in levels of ctDNA (Phase II)	Monitoring of ctDNA levels in correlation with disease free survival	At 4-6 weeks after treatment

Collaborators and Investigators

• Sponsor: Roswell Park Cancer Institute
• Collaborators: National Center for Advancing Translational Sciences (NCATS)
• Investigators: Principal Investigator: Anthony S Dakwar, Roswell Park Cancer Institute

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2024
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: February 27, 2024
• First Submitted That Met QC Criteria: March 5, 2024
• First Posted (Actual): March 13, 2024

Study Record Updates

• Last Update Posted (Actual): April 24, 2024
• Last Update Submitted That Met QC Criteria: April 22, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Disease Attributes; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Carcinoma; Colorectal Neoplasms; Recurrence; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Photosensitizing Agents; Dermatologic Agents; Aminolevulinic Acid; Levulinic acid
• Other Study ID Numbers: I-3670923 (Other Identifier: Roswell Park Cancer Institute); UL1TR001412 (U.S. NIH Grant/Contract); NCI-2024-01256 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes