Clinical trial NCT06307548: Fluorescence Image Guided Surgery Followed by Intraoperative Photodynamic Therapy for Improving Local Tumor Control in Patients With Locally Advanced or Recurrent Colorectal Cancer
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Locally Advanced Colorectal Carcinoma
Recurrent Colorectal Carcinoma
Stage III Colorectal Cancer
Lead sponsor: Roswell Park Cancer Institute
Sponsor class: OTHER
Collaborators: name: National Center for Advancing Translational Sciences (NCATS)
First posted: 2024-03-13
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Accuracy of the fluorescence imaging (Phase I)
timeFrame: Up to 3 years
measure: Incidence of adverse events (Phase I)
timeFrame: Up to 30 days post-therapy
measure: Evidence of disease (Phase II)
timeFrame: At 12 weeks post treatment
measure: Changes in carcinoembryonic antigen (CEA) and circulating tumor deoxyribonucleic acid (ctDNA) (Phase II)
timeFrame: Within 4 weeks prior to surgical/PDT intervention and 4-6 weeks after treatment
Secondary outcomes:
measure: Changes in CEA and ctDNA (Phase I)
timeFrame: At 4 weeks prior to surgical/PDT intervention and 4-6 weeks after treatment
measure: Rate of recurrence (Phase I)
timeFrame: At approximately 3 months post treatment, and during long term followup will be part (every 3 to 6 months up to 3 years)
measure: Rate of local recurrence (Phase II)
timeFrame: Within 3 years post treatment during standard of care follow ups
measure: Disease free survival (Phase II)
timeFrame: Up to 3 years after treatment
measure: Correlation between disease free survival and changes in levels of CEA (Phase II)
timeFrame: At 4-6 weeks after treatment
measure: Correlation between disease free survival and changes in levels of ctDNA (Phase II)
timeFrame: At 4-6 weeks after treatment
Other outcomes:
Locations:
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
Study officials:
affiliation: Roswell Park Cancer Institute
name: Anthony S Dakwar
role: PRINCIPAL_INVESTIGATOR
References: