Fluorescence-Guided Surgery and Photodynamic Therapy for Colorectal Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Roswell Park Cancer Institute

Disqualifiers: Pregnancy, Porphyria, Liver dysfunction, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 1 day

21 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to improve surgery outcomes for colorectal cancer that has spread nearby or returned after treatment. The approach uses aminolevulinic acid (also known as Levulan or Levulan Kerastick) to make cancer cells glow under a specific light, aiding surgeons in spotting and removing them more effectively. After surgery, light therapy targets any remaining cancer cells. Individuals with locally advanced or recurrent colorectal cancer preparing for surgery might be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative approach.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What prior data suggests that this method is safe for colorectal cancer patients?

Research has shown that aminolevulinic acid, used in special surgeries and light-based treatments, has been studied for its safety in treating colorectal cancer. Studies have found that this treatment can help doctors see and remove cancer more effectively. However, some side effects have been reported. High doses of aminolevulinic acid can cause nausea, liver problems, and a stuffy nose.

This treatment has been used in other cancer therapies, providing some evidence of its safety. Since this trial is in the early stages, researchers are closely monitoring the treatment for side effects in participants. More information on its safety will be collected as the study progresses. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment for colorectal cancer?

Researchers are excited about this treatment because it offers a novel approach to tackling colorectal cancer. Unlike traditional treatments that may rely solely on surgery or chemotherapy, this method uses aminolevulinic acid to enhance fluorescence-guided surgery and photodynamic therapy (PDT). This combination allows surgeons to see cancer tissues more clearly and target them precisely, potentially improving surgical outcomes and reducing recurrence. Additionally, the intraoperative PDT targets cancer cells with light-activated compounds, which is a unique mechanism compared to standard treatments. This approach could lead to more effective and less invasive treatment for patients.

What evidence suggests that fluorescence-guided surgery and photodynamic therapy could be effective for colorectal cancer?

Research has shown that using aminolevulinic acid in a special type of surgery can help doctors see and remove more of the tumor. In this trial, participants will receive aminolevulinic acid before surgery to potentially enhance tumor visibility and removal. Additionally, the trial will explore using aminolevulinic acid in photodynamic therapy (PDT) to potentially kill leftover cancer cells by activating a drug inside them with light. Early results from previous studies indicated that this combination could improve outcomes for patients with advanced or returning colorectal cancer. These findings offer promise for patients seeking new treatment options. ^{4 6 7 8 9}

Who Is on the Research Team?

Anthony S Dakwar

Principal Investigator

Roswell Park Cancer Institute

Are You a Good Fit for This Trial?

This trial is for patients with colorectal cancer that has spread to nearby areas or returned after treatment. Participants should be suitable for surgery and photodynamic therapy, but specific inclusion and exclusion criteria are not provided.

Inclusion Criteria

I can take care of myself but may not be able to do heavy physical work.

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

Amenable to diagnostic CT and MR imaging

Exclusion Criteria

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

Pregnant or nursing female participants

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive aminolevulinic acid orally 2 to 4 hours prior to surgery, followed by image-guided fluorescence and intraoperative photodynamic therapy

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including CT or MRI scans and blood sample collection

3 years

Visits every 3 to 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Aminolevulinic Acid

Trial Overview The study tests a two-step treatment: first, surgeons use a special drug (aminolevulinic acid) that makes cancer cells glow under blue light during surgery; then they apply red laser light to kill any remaining cancer cells using photodynamic therapy.

How Is the Trial Designed?

Group I: Treatment (aminolevulinic, fluorescence-guided surgery, PDT) Experimental Treatment 7 Interventions

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.

Aminolevulinic Acid is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Levulan Kerastick for:

• Actinic keratosis
• Moderate to severe acne vulgaris

Approved in European Union as Levulan for:

• Actinic keratosis
• Moderate to severe acne vulgaris

Approved in Canada as Levulan Kerastick for:

• Actinic keratosis

Who Is Running the Clinical Trial?

Roswell Park Cancer Institute

Lead Sponsor

Trials

427

Recruited

40,500+

National Center for Advancing Translational Sciences (NCATS)

Collaborator

Trials

394

Recruited

404,000+

Published Research Related to This Trial

Photodynamic therapy (PDT) using aminolevulinic acid (ALA) has become a highly effective treatment for actinic keratoses, with the FDA approving Levulan Kerastick as the preferred topical solution.

Levulan is well tolerated by patients and provides excellent cosmetic outcomes with only minor side effects, making it a safe option for treating skin tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aminolevulinic acid (Levulan) in photodynamic therapy of actinic keratoses. Lang, K., Schulte, KW., Ruzicka, T., et al.[2017]

In a study involving 36 patients, topical application of 20% aminolevulinic acid (ALA) followed by exposure to blue light resulted in an 88% complete clearance of actinic keratoses (AKs) after 8 weeks, demonstrating high efficacy.

The treatment was conducted in a multicenter, randomized, vehicle-controlled design, confirming that photodynamic therapy with ALA and blue light is a safe and effective option for managing multiple AKs on the face and scalp.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Photodynamic therapy of actinic keratoses with topical aminolevulinic acid hydrochloride and fluorescent blue light. Jeffes, EW., McCullough, JL., Weinstein, GD., et al.[2013]

Delta aminolevulinic acid (5ALA) is an FDA-approved fluorescent agent that enhances the visualization of tumors during surgery, particularly effective for glioma surgery, and shows promise in other surgical fields such as dermatology and urology.

5ALA has demonstrated high sensitivity in labeling malignant tissues, allowing surgeons to identify cancerous areas that may not be visible with standard lighting, with minimal side effects reported, such as potential skin irritation from sun exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delta-Aminolevulinic Acid-Mediated Photodiagnoses in Surgical Oncology: A Historical Review of Clinical Trials. Georges, JF., Valeri, A., Wang, H., et al.[2020]

5-Aminolevulinic acid (ALA) is a unique photodynamic therapy agent that acts as a precursor to the photosensitizer protoporphyrin IX (PpIX), which can effectively treat various skin conditions like basal cell carcinoma and actinic keratoses when applied topically and exposed to light.

ALA has also shown promise in internal applications for selective endometrial ablation and as a fluorescence marker for cancer detection in clinical studies, indicating its versatility in both treatment and diagnostic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Photodynamic therapy (PDT) and photodiagnosis (PD) using endogenous photosensitization induced by 5-aminolevulinic acid (ALA): mechanisms and clinical results. Kennedy, JC., Marcus, SL., Pottier, RH.[2016]

In a feasibility study involving 23 patients with 27 colorectal lesions, endoscopic fluorescence imaging (EFI) after oral administration of 5-aminolevulinic acid (5-ALA) showed high visibility of superficial colorectal tumors, particularly with increasing dysplasia severity.

The study found that 5-ALA was safe to use, with no significant adverse events reported, suggesting it could be a promising technique for real-time imaging of colorectal tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating the efficacy and safety of a novel endoscopic fluorescence imaging modality using oral 5-aminolevulinic acid for colorectal tumors. Tsuruki, ES., Saito, Y., Abe, S., et al.[2020]

Photodynamic therapy using 5-aminolevulinic acid and light activation has shown significant improvement in severe cystic acne, including reduced lesion count and enhanced skin texture.

The treatment also effectively smoothed scar edges in a patient with class 4 facial cystic acne, indicating its potential as a therapeutic option for severe acne and associated scarring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cystic acne improved by photodynamic therapy with short-contact 5-aminolevulinic acid and sequential combination of intense pulsed light and blue light activation. Melnick, S.[2022]

Aminolevulinic acid hydrochloride (ALA) is increasingly recognized as a key drug in photodynamic therapy (PDT) for treating various epithelial tumors, particularly in dermatology for actinic keratoses and superficial basal cell carcinomas.

ALA not only serves as an effective treatment but also aids in the diagnosis of neoplastic tissues through its fluorescence properties, making it valuable across multiple medical fields including gastroenterology and pulmonology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aminolevulinic acid: pharmacological profile and clinical indication. Lang, K., Lehmann, P., Bolsen, K., et al.[2019]

The self-adhesive 5-ALA patch used in photodynamic therapy (PDT) for actinic keratosis (AK) showed good efficacy, with complete response in 3 out of 10 patients and partial response in 7 patients after a single treatment session.

The treatment was well-tolerated overall, with local adverse events reported in only 4 patients, indicating that the 5-ALA patch is a safe and convenient option for PDT in AK management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Photodynamic Therapy with 5-Aminolevulinic Acid Patch for the Treatment of Actinic Keratosis. Kiss, N., Farkas, K., Tosti, G., et al.[2022]

In a study of 33 patients with malignant gliomas, 'strong' fluorescence from 5-aminolevulinic acid indicated solid tumors with high cell density, while 'weak' fluorescence suggested infiltrating tumors with lower cell density, demonstrating the utility of fluorescence in guiding surgical resections.

The study found that macroscopic fluorescence was more effective than MRI contrast enhancement in detecting residual tumors, with a 100% positive predictive value for strongly fluorescing tissue and a 95% value for weakly fluorescing tissue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

5-Aminolevulinic acid-derived tumor fluorescence: the diagnostic accuracy of visible fluorescence qualities as corroborated by spectrometry and histology and postoperative imaging. Stummer, W., Tonn, JC., Goetz, C., et al.[2022]

The study found that esterified derivatives of 5-aminolevulinic acid (ALA), such as ALA-hexylester, ALA-methylester, and ALA-benzylester, achieved similar or higher fluorescence intensities in rat colonic tissue compared to ALA, but at significantly lower concentrations, indicating improved uptake and distribution.

Peak fluorescence for all compounds occurred at specific time points after application, with ALA esters requiring 13-18 times lower concentrations to achieve comparable fluorescence levels, suggesting they may enhance the effectiveness of photodynamic diagnosis and therapy for detecting malignant lesions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protoporphyrin IX distribution following local application of 5-aminolevulinic acid and its esterified derivatives in the tissue layers of the normal rat colon. Endlicher, E., Rümmele, P., Hausmann, F., et al.[2018]

5-Aminolaevulinic acid (ALA) is a safe and effective agent for photodynamic therapy (PDT) in treating gastrointestinal tumors, with a favorable safety profile as it only causes skin photosensitivity for 1-2 days.

In a study of 26 patients, ALA showed better tumor selectivity in the colon at higher doses (60 mg/kg), leading to significant tumor necrosis after treatment with red light, indicating its potential for larger lesions with further optimization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sensitization and photodynamic therapy (PDT) of gastrointestinal tumors with 5-aminolaevulinic acid (ALA) induced protoporphyrin IX (PPIX). A pilot study. Mĺkvy, P., Messmann, H., Regula, J., et al.[2016]

Topical administration of 5-aminolevulinic acid (5-ALA) in varying concentrations showed promising results for photodynamic therapy (PDT) in treating gut cancer in a mouse model, indicating its potential as a localized treatment option.

While topical application achieved satisfactory fluorescence levels in gut tissues, systemic administration resulted in higher fluorescence intensity, suggesting that while 5-ALA can be used topically, systemic delivery may enhance its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical versus Systemic 5-Aminolevulinic Acid Administration for Photodynamic Therapy of the Colon in B10.RBP Mice. Gil, M., Woszczynski, M., Regula, J., et al.[2019]

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