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

Recurrent Colorectal Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06307548
• Other study ID #: I-3670923
• Secondary ID: NCI-2024-01256I-
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: June 1, 2024
• Est. completion date: June 1, 2027

Study information

• Verified date: May 2024
• Source: Roswell Park Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

PRIMARY OBJECTIVES:

• To test the accuracy of image-guided fluorescence to detect residual disease. (Phase I)

• 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)

• To determine the potential efficacy of intraoperative PDT (after image-guided fluorescence surgery). (Phase II)

SECONDARY OBJECTIVES:

• To assess the relationship between disease free survival and changes in levels of carcinoembryonic antigen (CEA) and circulating tumor DNA (ctDNA). (Phase II)

• 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 21
• Est. completion date: June 1, 2027
• Est. primary completion date: June 1, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Colorectal Neoplasms
• Locally Advanced Colorectal Carcinoma
• Recurrence
• Recurrent Colorectal Carcinoma
• Stage III Colorectal Cancer

Intervention

Drug:
• Aminolevulinic Acid
Given PO

Procedure:
• Biospecimen Collection
Undergo blood sample collection
• Computed Tomography
Undergo CT
• Fluorescence-Guided Surgery
Undergo fluorescence-guided surgery
• Magnetic Resonance Imaging
Undergo MRI

Drug:
• Photodynamic Therapy
Undergo PDT

Procedure:
• Surgical Procedure
Undergo surgery

Locations

Country	Name	City	State
United States	Roswell Park Cancer Institute	Buffalo	New York

Sponsors (2)

Lead Sponsor	Collaborator
Roswell Park Cancer Institute	National Center for Advancing Translational Sciences (NCATS)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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