5-ALA Photodynamic Therapy for Cancer

Overseen By Alex Martinez

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Fox Chase Cancer Center

Must not be taking: Steroids, Intravenous antibiotics

Disqualifiers: Symptomatic brain metastases, Active infections, HIV/AIDS, Recent cardiovascular events, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

130 Participants Needed

Trial Summary

What is the purpose of this trial?

RDT aims to take advantage of the relatively safer toxicity profiles of both lower dose radiation therapy and systemic ALA to treat non-superficial lesions in a manner similar to photodynamic therapy. The doses of radiation administered in this study will be lower than those typically used to treat cancer. However, with administration of ALA, which has been shown to be selectively concentrated in neoplastic cells, it is reasonable to expect responses in the target lesion(s) with relative sparing of nearby normal structures. A similar therapy is currently being used in a single institution in China. Members of the Fox Chase Cancer Center have visited the Chinese medical site multiple times and have gained first-hand experience with this therapy. Based on thus-far unpublished data, this treatment appears to be both safe and well-tolerated. There have been marked responses seen in some of these patients, but this therapy has not yet been investigated in a more formalized clinical trial setting, nor has it been used on Western patients. Thus, while these findings are encouraging, much work is necessary to determine the efficacy and role of this intervention.

Do I need to stop my current medications to join the trial?

The trial requires that all previous cancer therapies, including radiotherapy, major surgery, and investigational therapies, be stopped for at least 14 days before starting the trial treatment. However, the protocol does not specify if you need to stop other non-cancer medications.

What data supports the effectiveness of the treatment 5-ALA Photodynamic Therapy for Cancer?

Research shows that 5-ALA, when used in photodynamic therapy, can effectively target and kill cancer cells by accumulating a light-sensitive substance in tumors, which is then activated by light to destroy the cells. Studies have demonstrated its effectiveness in various cancer types, including stomach and bladder cancer, by significantly slowing tumor growth and improving treatment outcomes. ^{1 2 3 4 5}

Is 5-ALA photodynamic therapy generally safe for humans?

5-ALA photodynamic therapy is generally considered safe, but it can cause some side effects like nausea, vomiting, and temporary liver function changes. Some patients may experience low blood pressure during treatment, and there is a risk of skin sensitivity to light for a short period. ^{6 7 8 9 10}

What makes 5-ALA photodynamic therapy unique for cancer treatment?

5-ALA photodynamic therapy is unique because it uses a naturally occurring compound that is converted into a photosensitive product in cancer cells, allowing targeted treatment with light exposure. Unlike synthetic photosensitizers, 5-ALA is rapidly metabolized, reducing the risk of prolonged skin sensitivity to light. ^{2 7 11 12 13}

Eligibility Criteria

Adults with advanced solid tumors resistant to standard therapy or without available standard options can join. They must have finished previous cancer treatments at least 14 days prior and be in stable condition, with good organ function and blood pressure. Participants need the ability to undergo PET/MRI imaging, not have active infections requiring IV treatment, no HIV/AIDS-related illness, not be pregnant or breastfeeding, and agree to use effective contraception.

Inclusion Criteria

My kidney function tests are within the required range.

I must be able to undergo PET/MRI imaging to participate.

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

Exclusion Criteria

You have a known history of porphyria, a medical condition that affects how your body produces certain substances.

You have a serious medical or mental health condition, or abnormal lab results, that could make it risky for you to participate in the study or affect the study results.

I am currently being treated for a minor infection with pills.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive orally-administered 5-aminolevulinic acid (ALA) as a radiosensitizer prior to low-dose radiation therapy

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• 5-ALA

Trial Overview The trial is testing a combination of low-dose radiation therapy and systemic ALA (5-aminolevulinic acid) on non-superficial lesions. This approach aims for targeted responses while sparing healthy tissue. It's based on promising but unpublished Chinese data showing safety and marked responses in some patients.

Participant Groups

Group I: 5-ALA Experimental Treatment 1 Intervention

orally-administered 5-aminolevulinic acid (ALA) given as a radiosensitizer prior to low-dose radiation therapy (RT)

5-ALA is already approved in United States, European Union for the following indications:

Approved in United States as 5-aminolevulinic acid for:

• Actinic keratosis
• Visualization of malignant tissue during glioma surgery

Approved in European Union as 5-aminolevulinic acid for:

• Visualization of malignant tissue during glioma surgery

Who Is Running the Clinical Trial?

Fox Chase Cancer Center

Lead Sponsor

Trials

236

Recruited

39,300+

Findings from Research

5-Aminolevulinic acid is a highly specific photosensitizer that has been effectively used in diagnosing and treating urological cancers, particularly bladder cancer, through techniques like photodynamic diagnosis and therapy.

This compound works by exploiting the Warburg effect, a common characteristic of cancer cells, suggesting its potential application in treating a wide range of cancer types beyond urological cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current status of photodynamic technology for urothelial cancer. Inoue, K., Fukuhara, H., Yamamoto, S., et al.[2022]

5-Aminolevulinic acid (5-ALA) combined with photodynamic therapy (ALA-PDT) using violet and green LEDs was effective in treating peritoneally disseminated gastric cancer in a mouse model, showing significant necrotic areas in cancer nodules compared to controls.

The study found that violet and green LEDs generated more reactive oxygen species and had stronger anticancer effects than red LEDs, highlighting the importance of selecting the optimal light wavelength for effective treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

5-Aminolevulinic acid-mediated photodynamic therapy using light-emitting diodes of different wavelengths in a mouse model of peritoneally disseminated gastric cancer. Hino, H., Murayama, Y., Nakanishi, M., et al.[2013]

A systematic review of 77 studies on 5-aminolevulinic acid (5-ALA) photodynamic therapy (PDT) showed that it is particularly effective against stomach cancer, indicating a cancer-type sensitivity to this treatment.

The review suggests the need for a standardized experimental protocol for 5-ALA PDT to improve consistency and reliability in future research and clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic Review and Meta-Analysis of In Vitro Anti-Human Cancer Experiments Investigating the Use of 5-Aminolevulinic Acid (5-ALA) for Photodynamic Therapy. Shinoda, Y., Kato, D., Ando, R., et al.[2021]

A single illumination of nodular tumors with red light after systemic administration of 5-aminolevulinic acid (ALA) significantly slowed tumor growth, with a doubling time of 6.6 days compared to 1.7 days in untreated controls.

The most effective treatment involved illuminating the tumors twice, at both 1 and 2.5 hours after ALA administration, which resulted in a remarkable tumor doubling time of 18.9 days, likely due to the enhanced formation of protoporphyrin IX between illuminations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improvement of systemic 5-aminolevulinic acid-based photodynamic therapy in vivo using light fractionation with a 75-minute interval. de Bruijn, HS., van der Veen, N., Robinson, DJ., et al.[2013]

In a mouse model of Lewis lung carcinoma, the combination of 5-Aminolevulinic acid (ALA) and hyperthermotherapy (HT) significantly inhibited tumor growth compared to HT alone, with tumor size increases being only 1.3 and 1.1 times in the HT+ALA groups versus much larger increases in control and HT groups.

ALA administration led to the accumulation of protoporphyrin IX (PpIX) in tumors, enhancing the antitumor effect of HT, indicating that ALA can be an effective adjunct treatment in photodynamic therapy for tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor effect of combination of hyperthermotherapy and 5-aminolevulinic acid (ALA). Takahashi, K., Hasegawa, T., Ishii, T., et al.[2016]

A 68-year-old man experienced severe hypotension (blood pressure dropping to 47/32 mmHg) after receiving 5-aminolevulinic acid (5-ALA) for bladder tumor surgery, highlighting a significant adverse effect associated with this drug.

Standard treatments for hypotension, such as phenylephrine and ephedrine, were ineffective, necessitating the use of adrenaline to stabilize blood pressure, suggesting that anesthesiologists should be cautious and consider 5-ALA as a potential cause of hypotension during procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

5-Aminolevulinic acid-induced severe hypotension during transurethral resection of a bladder tumor: a case report. Yatabe, T., Marie, SL., Fukuhara, H., et al.[2020]

5-aminolaevulinic acid (ALA) shows promise as a photosensitizer for photodynamic therapy (PDT) in cancer, with significant localization in the perinuclear cytoplasm and nucleus of CPAE and PTK2 cells, indicating targeted areas for treatment.

Subcellular phototoxicity studies revealed that the nucleus and perinuclear regions are the most sensitive to ALA-induced damage, while the peripheral cytoplasm showed minimal sensitivity, suggesting a strategic approach for maximizing therapeutic effects while minimizing damage to healthy cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcellular phototoxicity of 5-aminolaevulinic acid (ALA). Liang, H., Shin, DS., Lee, YE., et al.[2019]

Aminolevulinic acid (ALA) at doses up to 60 mg/kg has minimal side effects in patients undergoing abdominal surgery, with only nausea and vomiting reported in 20% of cases and transient abnormal liver functions in nearly a quarter of patients.

The study found that protoporphyrin IX (PpIX) concentrations were significantly higher in tumors compared to other tissues, indicating that ALA can effectively enhance photosensitization for photodynamic therapy in treating gastrointestinal adenocarcinomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Side effects and photosensitization of human tissues after aminolevulinic acid. Webber, J., Kessel, D., Fromm, D.[2016]

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]

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]

The combination of 5-aminolevulinic acid (5-ALA) with 5% α-bisabolol significantly enhances the retention of 5-ALA in porcine buccal mucosa, achieving six times higher retention compared to 5-ALA alone after 4 hours, which is crucial for effective photodynamic therapy (PDT).

Histopathological analysis indicated that α-bisabolol alters the tissue morphology, likely contributing to improved retention of 5-ALA, suggesting that it could be a valuable adjuvant in PDT formulations for oral cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

α-Bisabolol improves 5-aminolevulinic acid retention in buccal tissues: Potential application in the photodynamic therapy of oral cancer. Quintanilha, NP., Dos Santos Miranda Costa, I., Freiman de Souza Ramos, M., et al.[2019]

5-Aminolaevulinic acid (ALA) is an effective photosensitiser used in photodynamic therapy (PDT) for treating cancer and pre-malignant conditions, offering a significant advantage due to its rapid metabolism that reduces skin sensitivity after treatment.

ALA has a wide range of clinical applications in PDT and photodiagnosis, making it a versatile therapeutic option compared to synthetic photosensitisers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of 5-aminolaevulinic acid as a photosensitiser in photodynamic therapy and photodiagnosis. Kelty, CJ., Brown, NJ., Reed, MW., et al.[2019]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Current status of photodynamic technology for urothelial cancer. [2022]

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

5-Aminolevulinic acid-mediated photodynamic therapy using light-emitting diodes of different wavelengths in a mouse model of peritoneally disseminated gastric cancer. [2013]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Systematic Review and Meta-Analysis of In Vitro Anti-Human Cancer Experiments Investigating the Use of 5-Aminolevulinic Acid (5-ALA) for Photodynamic Therapy. [2021]

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

Improvement of systemic 5-aminolevulinic acid-based photodynamic therapy in vivo using light fractionation with a 75-minute interval. [2013]

5. Greece pubmed.ncbi.nlm.nih.gov

Antitumor effect of combination of hyperthermotherapy and 5-aminolevulinic acid (ALA). [2016]

6. Germany pubmed.ncbi.nlm.nih.gov

5-Aminolevulinic acid-induced severe hypotension during transurethral resection of a bladder tumor: a case report. [2020]

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

Subcellular phototoxicity of 5-aminolaevulinic acid (ALA). [2019]

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

Side effects and photosensitization of human tissues after aminolevulinic acid. [2016]

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

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

10. 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]

11. Switzerland pubmed.ncbi.nlm.nih.gov

α-Bisabolol improves 5-aminolevulinic acid retention in buccal tissues: Potential application in the photodynamic therapy of oral cancer. [2019]

12. England pubmed.ncbi.nlm.nih.gov

The use of 5-aminolaevulinic acid as a photosensitiser in photodynamic therapy and photodiagnosis. [2019]

13. 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]