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

Trial Summary

What is the purpose of this trial?

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.

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 data supports the effectiveness of the treatment Aminolevulinic Acid, Levulan, Levulan Kerastick, Aminolevulinic Acid, ALA for colorectal cancer?

Research shows that 5-aminolevulinic acid (5-ALA) is effective in photodynamic therapy (PDT) for various gastrointestinal tumors, including colorectal cancer, by inducing a photosensitizer that helps target cancer cells when exposed to light. Studies have demonstrated its potential in treating tumors with minimal side effects, making it a promising option for colorectal cancer treatment. ^{1 2 3 4 5}

Is Aminolevulinic Acid (ALA) safe for use in humans?

Aminolevulinic Acid (ALA), used in photodynamic therapy, is generally well-tolerated with minor side effects, such as skin photosensitivity for 1-2 days and occasional mild nausea. It has been safely used for conditions like actinic keratosis and cystic acne, showing good tolerability and cosmetic outcomes. ^{1 6 7 8 9}

How does the drug Aminolevulinic Acid differ from other treatments for colorectal cancer?

Aminolevulinic Acid is unique because it is used in fluorescence-guided surgery and photodynamic therapy, where it helps visualize and target cancerous tissues by making them glow under specific light. This approach allows for more precise removal of tumors compared to traditional methods. ^{1 3 10 11 12}

Research Team

Anthony S Dakwar

Principal Investigator

Roswell Park Cancer Institute

Eligibility Criteria

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.

I am 18 years old or older.

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

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 (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]

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 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]

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]

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]

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]

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]

References

1. Slovakia 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. [2016]

2. United States pubmed.ncbi.nlm.nih.gov

Photodynamic therapy (PDT) and photodiagnosis (PD) using endogenous photosensitization induced by 5-aminolevulinic acid (ALA): mechanisms and clinical results. [2016]

3. United States pubmed.ncbi.nlm.nih.gov

Topical versus Systemic 5-Aminolevulinic Acid Administration for Photodynamic Therapy of the Colon in B10.RBP Mice. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Aminolevulinic acid: pharmacological profile and clinical indication. [2019]

5. Germany 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. [2020]

6. Canada pubmed.ncbi.nlm.nih.gov

Aminolevulinic acid (Levulan) in photodynamic therapy of actinic keratoses. [2017]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Photodynamic Therapy with 5-Aminolevulinic Acid Patch for the Treatment of Actinic Keratosis. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Photodynamic therapy of actinic keratoses with topical aminolevulinic acid hydrochloride and fluorescent blue light. [2013]

9. United States 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. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Delta-Aminolevulinic Acid-Mediated Photodiagnoses in Surgical Oncology: A Historical Review of Clinical Trials. [2020]

11. England 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. [2018]

12. United States 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. [2022]