Fluorescence-Guided Surgery and Photodynamic Therapy for Colorectal Cancer
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Roswell Park Cancer Institute
Disqualifiers: Pregnancy, Porphyria, Liver dysfunction, others
No Placebo Group
Approved in 3 Jurisdictions
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.
12345Is 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.
16789How 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.
13101112Eligibility 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
+3 more
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
+5 more
Trial 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
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: Treatment (aminolevulinic, fluorescence-guided surgery, PDT)Experimental Treatment7 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Roswell Park Cancer InstituteBuffalo, NY
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Who Is Running the Clinical Trial?
Roswell Park Cancer InstituteLead Sponsor
National Center for Advancing Translational Sciences (NCATS)Collaborator
References
Sensitization and photodynamic therapy (PDT) of gastrointestinal tumors with 5-aminolaevulinic acid (ALA) induced protoporphyrin IX (PPIX). A pilot study. [2016]5-Aminolaevulinic acid (ALA) is a promising agent for photodynamic therapy (PDT) sensitization as it can be given orally and only causes skin photosensitivity for 1-2 days. In fluorescence and photodynamic studies 26 patients with benign and malignant gastrointestinal tumors were given 30-60 mg ALA orally (single or divided doses) and biopsies were taken of tumor and normal tissue at 1-24 hours for fluorescence microscopy. With 30 mg/kg, highest protoporphyrin IX (PPIX) levels were seen in esophagus, duodenum and less in colon, but without tumor selectivity. Better tumor selectivity was seen in colon after 60 mg/kg (5:1). Six patients had transient rises in transaminases and five mild nausea. Sixteen patients were later treated (after further ALA) with red light (628 nm, bare or diffuser fibre, 50-100 J at 50 mW at each site). All but two showed subsequent necrosis, but only 0.5-1.5 mm of depth. PDT with ALA is simple, safe and promising for tumors in the gastrointestinal tract. Modification of treatment parameters may make it suitable for larger lesions.
Photodynamic therapy (PDT) and photodiagnosis (PD) using endogenous photosensitization induced by 5-aminolevulinic acid (ALA): mechanisms and clinical results. [2016]5-Aminolevulinic acid (ALA), when added to many tissues, results in the accumulation of sufficient quantities of the endogenous photosensitizer protoporphyrin IX (PpIX) via the heme biosynthetic pathway, to produce a photodynamic effect when exposed to activating light. Therefore, ALA is the only photodynamic therapy (PDT) agent in current clinical development that is a biochemical precursor of a photosensitizer. Topical ALA application, followed by exposure to activating light (ALA PDT), has been reported effective for the treatment of a variety of dermatologic diseases including cutaneous superficial and nodular basal cell carcinoma, Bowen's disease, and actinic (solar) keratoses. Local internal application of ALA has also been used for selective endometrial ablation in animal model systems and in human clinical studies has shown selective formation of PpIX within the endometrium. PpIX induced by ALA application has also been used as a fluorescence detection marker for photodiagnosis (PD) of cancer and dysplastic conditions of the urinary bladder and other organs. Systemic, oral administration of ALA has been used for ALA PDT of superficial head and neck cancer, various gastrointestinal cancers, and the condition known as Barrett's esophagus. The current state of knowledge of the mechanisms of endogenous topical and systemic photosensitization using ALA, the results of published clinical trials, and possible methods of increasing the efficacy of endogenous photosensitization for ALA PDT are reviewed in this paper.
Topical versus Systemic 5-Aminolevulinic Acid Administration for Photodynamic Therapy of the Colon in B10.RBP Mice. [2019]5-aminolevulinic acid (5-ALA) is an interesting photosensitizing substance for photodynamic therapy (PDT), successfully applied topically for urological malignancy. In gastroenetrology it has proven efficacy for treatment of some GI neoplasms after systemic administration. This study was aimed at investigating the possibility of topical 5-ALA administration also for the PDT of gut cancer in a mice model. 5-ALA solution at different concentrations (5%, 1.5%, and 0.5%) was instilled in the colon of mice, which was later removed and examined by fluorescence microscopy. The results of fluorescence studies were compared with those obtained in a control group treated with 5-ALA given systemically. Satisfactory epithelial fluorescence levels and good selectivity between gut layers was obtained after intracolonic 5-ALA instillation. However, mean fluorescence intensity was higher after systemic drug application. Our results suggest that 5-ALA may probably be used topically for the PDT of some gut neoplasms. © 1999 Society of Photo-Optical Instrumentation Engineers.
Aminolevulinic acid: pharmacological profile and clinical indication. [2019]The role of aminolevulinic acid hydrochloride (ALA) in photodynamic therapy (PDT) of in situ neoplasias and tumours of epithelial tumours is steadily increasing and it has been shown to be the drug with most clinical use in PDT. In dermatology, topical PDT with ALA is already postulated to be the treatment of choice for actinic keratoses and superficial basal cell carcinomas. In gastroenterology, pulmonology, uro- and nephrology, neurology and gynaecology ALA has an important role as a photosensitiser not only in the diagnosis of neoplastic tissue but as therapy; first experiences have been made with PDT in these organs. Besides the therapeutic efficacy of this technique, the fluorescence of ALA-induced porphyrins can be effectively used to detect and delineate epithelial and endothelial neoplasms. In dermatology, other indications for ALA-treatment are non-tumoural applications, especially psoriasis, viral-induced diseases, or acne vulgaris. ALA is an effective compound in the diagnosis or therapy of various epithelial and endothelial neoplastic lesions.
Evaluating the efficacy and safety of a novel endoscopic fluorescence imaging modality using oral 5-aminolevulinic acid for colorectal tumors. [2020]Five-aminolevulinic acid (5-ALA) is being increasingly used for photodynamic diagnosis and therapy of various types of tumors including brain, urologic, and other neoplasias. The use of 5-ALA to treat Barrett's carcinomas has been documented, but its clinical effectiveness for diagnosis of gastrointestinal tumors, particularly early cancers, remains unknown.
Aminolevulinic acid (Levulan) in photodynamic therapy of actinic keratoses. [2017]The role of photodynamic therapy (PDT) in the treatment of in situ neoplasias and tumors of the skin is steadily increasing. Its principles of photodynamic action include an intratumoral enriched photosensitizer and light activation. Aminolevulinic acid (ALA) has demonstrated highest efficacy in topical PDT, and has become the most clinically useful. For actinic (solar) keratoses, topical ALA-PDT using Levulan Kerastick (20% topical solution, DUSA Pharmaceuticals) is already postulated to be the treatment of choice. In December 1999, the US FDA approved this topical product for the treatment of actinic keratoses. Levulan is well tolerated and leads to excellent cosmetic results with only minor side effects.
Photodynamic Therapy with 5-Aminolevulinic Acid Patch for the Treatment of Actinic Keratosis. [2022]Photodynamic therapy (PDT) using 5-aminolevulinic acid (5-ALA) is an emerging treatment option in the care of actinic keratosis (AK). A self-adhesive 5-ALA patch was recently developed that allows a precise PDT procedure. Here, we review the current literature and report the findings of our case series that observed the outcomes and safety of 5-ALA patch PDT. Ten patients with a total of 40 AKs were treated with a single session of conventional or daylight PDT using 5-ALA patch at the Department of Dermatology and Venereology, Sapienza University of Rome or at the European Institute of Oncology, Milan, Italy. Complete response was observed in three patients, while partial response was seen in seven patients. Overall tolerability was good or excellent, with local adverse events observed in four patients. This is the first case series reported where the 5-ALA patch was applied using daylight PDT, and its efficacy and tolerability in the treatment of AK were demonstrated. In conclusion, the self-adhesive 5-ALA patch is a convenient application of PDT that provides a well-tolerated and effective treatment option with satisfactory cosmetic outcomes.
Photodynamic therapy of actinic keratoses with topical aminolevulinic acid hydrochloride and fluorescent blue light. [2013]Aminolevulinic acid hydrochloride (ALA, Levulan) applied topically to actinic keratoses (AKs) leads to accumulation of the photosensitizer protoporphyrin IX, which, when activated by exposure to light, eradicates AKs.
Cystic acne improved by photodynamic therapy with short-contact 5-aminolevulinic acid and sequential combination of intense pulsed light and blue light activation. [2022]Photodynamic therapy with short-contact 5-aminolevulinic acid (Levulan Kerastick, Dusa Pharmaceuticals, Inc.) and activation by intense pulsed light in an initial treatment and blue light in 3 subsequent treatments has resulted in significant improvement in severity of acne, reduction in the number of lesions, improvement in skin texture, and smoothing of scar edges in an Asian patient with severe (class 4) facial cystic acne and scarring.
Delta-Aminolevulinic Acid-Mediated Photodiagnoses in Surgical Oncology: A Historical Review of Clinical Trials. [2020]Fluorescence imaging is an emerging clinical technique for real-time intraoperative visualization of tumors and their boundaries. Though multiple fluorescent contrast agents are available in the basic sciences, few fluorescence agents are available for clinical use. Of the clinical fluorophores, delta aminolevulinic acid (5ALA) is unique for generating visible wavelength tumor-specific fluorescence. In 2017, 5ALA was FDA-approved for glioma surgery in the United States. Additionally, clinical studies suggest this agent may have utility in surgical subspecialties outside of neurosurgery. Data from dermatology, OB/GYN, urology, cardiothoracic surgery, and gastrointestinal surgery show 5ALA is helpful for intraoperative visualization of malignant tissues in multiple organ systems. This review summarizes data from English-language 5ALA clinical trials across surgical subspecialties. Imaging systems, routes of administration, dosing, efficacy, and related side effects are reviewed. We found that modified surgical microscopes and endoscopes are the preferred imaging devices. Systemic dosing across surgical specialties range between 5 and 30 mg/kg bodyweight. Multiple studies discussed potential for skin irritation with sun exposure, however this side effect is infrequently reported. Overall, 5ALA has shown high sensitivity for labeling malignant tissues and providing a means to visualize malignant tissue not apparent with standard operative light sources.
Protoporphyrin IX distribution following local application of 5-aminolevulinic acid and its esterified derivatives in the tissue layers of the normal rat colon. [2018]Photodynamic diagnosis and especially therapy after sensitization with 5-aminolevulinic acid (ALA) is hampered by limitations of uptake and distribution of ALA due to its hydrophilic nature. Chemical modification of ALA into its more lipophilic esters seems to be promising to overcome these problems. The aim of the present study was to investigate the comparative kinetics of protoporphyrin IX (PPIX) fluorescence in rat colonic tissue after topical application of ALA and its esterified derivatives, ALA-hexylester (h-ALA), ALA-methylester (m-ALA) and ALA-benzylester (b-ALA). Fluorescence intensity induced by PPIX in normal colonic tissue was quantified using fluorescence microscopy at 1, 2, 4, 6 and 8 h after sensitization. Mucosa exhibited higher fluorescence levels compared to the underlying submucosa or smooth muscle. Peak fluorescence intensities were seen 4 h after local sensitization with 86.0 mol ml(-1) ALA (513 +/- 0.57 counts per pixel), 6.6 mol ml(-1) m-ALA (508 +/- 35.50) and 4.8 mol ml(-1) h-ALA (532 +/- 128.80), and 6 h after sensitization with 4.6 mol ml(-1) b-ALA (468 +/- 190.27). A 13-18 times lower concentration of ALA esters was required for fluorescence intensities reached with ALA alone. A similar degree of the fluorescence ratio between mucosa and muscularis (5-6:1) was detected for ALA and its derivatives. The time point of the maximum value of this ratio was consistent with peak fluorescence levels for ALA and each ALA-ester. The clinical feasibility and the advantages of topical ALA ester-based fluorescence for detection of malignant and premalignant lesions need further investigations.
5-Aminolevulinic acid-derived tumor fluorescence: the diagnostic accuracy of visible fluorescence qualities as corroborated by spectrometry and histology and postoperative imaging. [2022]5-Aminolevulinic acid is used for fluorescence-guided resections. During resection, different macroscopic fluorescence qualities ("strong," "weak") can be distinguished that help guide resections.