ALA + Radiation for Solid Cancers

Overseen By Anthony Olszanski, MD

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, others

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

Compensation: Varies

Number of Visits: Unknown

130 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the safest and most effective doses of a new cancer treatment that combines 5-aminolevulinic acid (ALA) with low-dose radiation. The focus is on treating solid tumors that have spread and no longer respond to standard treatments. Researchers seek to understand the effectiveness of this combination and its side effects. Suitable participants have advanced solid tumors visible on imaging scans like PET or MRI and have exhausted standard treatment options. As a Phase 1 trial, the research focuses on understanding the treatment's effects in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires that all previous cancer therapies, including radiotherapy, major surgery, and investigational therapies, must be stopped for at least 14 days before starting the trial treatment. However, the protocol does not specify about other non-cancer medications, so it's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that 5-aminolevulinic acid (5-ALA), combined with low-dose radiation, is being explored as a potential treatment for solid tumors. Studies have found that 5-ALA can increase the sensitivity of cancer cells to radiation. This suggests the treatment might be effective even with lower radiation doses, potentially reducing side effects.

Early research has not identified any serious side effects directly linked to 5-ALA, and patients have generally tolerated it well. The radiation doses in these studies are lower than those in typical cancer treatments, which may also enhance safety.

Although this combination remains under study, initial results appear promising for prospective trial participants. It suggests the treatment could be relatively safe, but further research is necessary to confirm this. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about combining 5-aminolevulinic acid (ALA) with low-dose radiation because it introduces a unique approach to treating solid cancers. Unlike conventional treatments like surgery, chemotherapy, or high-dose radiation, this combination leverages ALA's ability to make cancer cells more sensitive to light and radiation. This means that the treatment could potentially target cancer cells more precisely, minimizing damage to surrounding healthy tissue. The hope is that this method will enhance the effectiveness of radiation therapy while reducing side effects, offering a more targeted and potentially safer option for patients.

What evidence suggests that ALA and low dose radiation might be an effective treatment for solid cancers?

Research has shown that 5-aminolevulinic acid (ALA) can increase cancer cells' sensitivity to radiation. In this trial, participants will receive a combination of ALA and low-dose radiation, potentially improving the targeting and destruction of cancer cells. Studies have found that ALA often aids in brain surgeries by helping doctors see and remove tumors more clearly. Researchers are studying its potential to enhance the effects of radiation on solid tumors. Early results suggest that this combination could effectively treat various types of cancer. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

Adults with advanced solid tumors resistant to standard treatments or without available standard therapies can join this trial. They must be able to undergo PET/MRI imaging, have stable vital signs and organ function, and not have had recent cancer treatments. Women of childbearing potential and men must agree to use contraception.

Inclusion Criteria

I am a woman who cannot become pregnant or will use birth control during and after the trial.

I am willing to undergo MRI imaging.

I have not been treated with bleomycin before radiation to my chest.

Exclusion Criteria

Patients with implanted battery-controlled devices (including, but not limited to, pacemakers and implanted cardiovascular defibrillator (AICDs)) that may suffer interference from neutron contamination of high energy photon beams

Pregnant or breast-feeding patients

I have HIV/AIDS but haven't been tested for this study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive 3 doses of ALA and fractions of radiation therapy during a 21-day cycle to determine the maximum tolerated dose (MTD)

3 weeks

Multiple visits (in-person)

Expansion

Cohorts are expanded to refine safety assessment and assess preliminary efficacy

56 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• 5-aminolevulinic Acid
• Low dose radiation

Trial Overview The study is testing the safety and effectiveness of combining low dose radiation (RT) with a drug called ALA in escalating doses. It aims to find the highest dose patients can tolerate without severe side effects, then expand the trial for further safety evaluation and preliminary efficacy results.

How Is the Trial Designed?

Group I: ALA / Fractions of Radiotherapy Experimental Treatment 1 Intervention

Subjects will receive 3 doses of ALA and fractions of radiation therapy during the course of one 21day cycle. Only one cycle per patient is allowed.

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

Approved in United States as Levulan for:

• Actinic keratoses of the face and scalp
• Visualization of glioma during surgery

Approved in European Union as Ameluz for:

• Actinic keratoses of the face and scalp
• Field-directed treatment of actinic keratoses of mild-to-moderate severity on the face and scalp

Approved in Canada as 5-Aminolevulinic acid for:

• Actinic keratoses of the face and scalp
• Visualization of glioma during surgery

Who Is Running the Clinical Trial?

Fox Chase Cancer Center

Lead Sponsor

Trials

236

Recruited

39,300+

Published Research Related to This Trial

In a study involving 28 patients with locally advanced and recurrent squamous cancers, the novel alpha-emitter radiation therapy (DaRT) demonstrated a high complete response rate of 78.6% for treated lesions, indicating its efficacy in tumor reduction.

The treatment was associated with manageable acute toxicities, primarily local pain and mild skin ulceration, with no severe grade 3 or higher toxicities reported, suggesting a favorable safety profile for this innovative therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial Safety and Tumor Control Results From a "First-in-Human" Multicenter Prospective Trial Evaluating a Novel Alpha-Emitting Radionuclide for the Treatment of Locally Advanced Recurrent Squamous Cell Carcinomas of the Skin and Head and Neck. Popovtzer, A., Rosenfeld, E., Mizrachi, A., et al.[2020]

In a study involving mice with human colon cancer, administration of 5-aminolevulinic acid (5-ALA) before X-ray irradiation significantly reduced tumor volume compared to mice that did not receive 5-ALA, indicating its potential as a radiosensitizer.

The results showed that multiple irradiations combined with 5-ALA treatment effectively inhibited tumor growth, suggesting that 5-ALA enhances the effectiveness of radiation therapy in colon cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Radiosensitizing effect of 5-aminolevulinic acid (5-ALA ) in Colon cancer]. Kamada, Y., Murayama, Y., Harada, K., et al.[2015]

5-aminolaevulinic acid (Ameluz) has been authorized for use in the European Union to treat mild to moderate actinic keratosis on the face and scalp, based on its effectiveness in improving the complete response rate of lesions.

The treatment involves applying the gel to the lesions and surrounding area, followed by illumination with red light, which activates a compound that destroys the target cells; common side effects include local reactions at the application site.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The European Medicines Agency approval of 5-aminolaevulinic acid (Ameluz) for the treatment of actinic keratosis of mild to moderate intensity on the face and scalp: summary of the scientific assessment of the Committee for Medicinal Products for Human Use. Tzogani, K., Straube, M., Hoppe, U., et al.[2018]

5-aminolaevulinic acid (ALA) effectively induces porphyrin photosensitization for photodynamic therapy (PDT) in pancreatic cancer, with the highest sensitization achieved through intravenous administration of 200 mg/kg ALA.

PDT using laser light resulted in significant tumor necrosis and improved survival in treated Syrian golden hamsters compared to untreated controls, indicating potential for ALA-PDT in treating pancreatic tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Photodynamic therapy using 5-aminolaevulinic acid for experimental pancreatic cancer--prolonged animal survival. Regula, J., Ravi, B., Bedwell, J., et al.[2019]

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]

Low doses of alpha radiation (1.36 and 6.8 cGy) can stimulate the proliferation of human lung adenocarcinoma (A549) cells, while higher doses (13.6-54.4 cGy) are cytotoxic, indicating a dose-dependent response.

In vivo studies showed that A549 cells exposed to low doses of alpha radiation resulted in significantly larger tumor volumes in SCID mice, suggesting that low-dose alpha radiation may promote tumor growth rather than inhibit it.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytoproliferative effect of low dose alpha radiation in human lung cancer cells is associated with connexin 43, caveolin-1, and survivin pathway. Rajan, V., Pandey, BN.[2021]

In a Phase I study involving 27 patients with locally advanced pancreatic or biliary carcinoma, significant toxicities were observed, with 8 patients experiencing severe side effects such as nausea, vomiting, and myelosuppression, indicating that the treatment regimen may be poorly tolerated.

The study suggests that older patients (over 70 years) and those with a lower performance status are at higher risk for severe toxicities, leading to a recommendation to limit the dose of 5-fluorouracil to 350 mg/m2/day to improve safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of combined radiation therapy with 5-fluorouracil and low dose folinic acid in patients with locally advanced pancreatic or biliary carcinoma. Hsue, V., Wong, CS., Moore, M., et al.[2019]

Using a dual delivery strategy for α-particle emitters in prostate cancer treatment significantly improves tumor growth inhibition compared to using a single delivery method, as shown in a mouse model.

This approach allows for more uniform irradiation of tumors, effectively targeting both avascular and perivascular regions, which may enhance the efficacy of α-particle radiotherapies for established tumors that are difficult to treat.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two diverse carriers are better than one: A case study in α-particle therapy for prostate specific membrane antigen-expressing prostate cancers. Salerno, D., Howe, A., Bhatavdekar, O., et al.[2022]

5-Aminolevulinic acid (ALA) enhances the accumulation of protoporphyrin IX (PpIX) in tumor cells, which increases the generation of reactive oxygen species (ROS) when combined with X-ray irradiation, leading to improved tumor cell death.

In a study involving mouse B16-BL6 melanoma cells, local administration of 50 mg/kg ALA before fractionated radiation therapy significantly improved tumor suppression, suggesting that ALA could enhance the effectiveness of cancer radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

5-Aminolevulinic acid enhances cancer radiotherapy in a mouse tumor model. Takahashi, J., Misawa, M., Murakami, M., et al.[2021]

The FAR therapy, a combination of 5-fluorouracil, vitamin A, and external radiation, was successfully administered to 95 patients with T2N0 glottic carcinoma, with 98% completing the treatment course.

This approach achieved a high local control rate of 91% and a 5-year disease-specific survival rate of 97%, while preserving laryngeal function in 91% of patients, indicating its efficacy and safety for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

"FAR" chemoradiotherapy improves laryngeal preservation rates in patients with T2N0 glottic carcinoma. Kumamoto, Y., Masuda, M., Kuratomi, Y., et al.[2013]

The combination of 5-fluorouracil (5-FU) and vitamin A significantly enhances the drug's ability to inhibit RNA formation and increases cellular sensitivity to radiation, making it more effective than 5-FU alone.

In a clinical study involving 275 patients with various head and neck cancers treated with the FAR therapy (5-FU, vitamin A, and cobalt-60 radiation) from 1972 to 1977, the treatment demonstrated highly effective synergism, suggesting a promising approach for cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synergistic combination therapy of 5-fluorouracil, vitamin A, and cobalt-60 radiation for head and neck tumors--antitumor combination therapy with vitamin A. Komiyama, S., Kudoh, S., Yanagita, T., et al.[2019]

Cisplatin, when used as a radiosensitizer in conjunction with radiation therapy for advanced squamous cell carcinoma of the head and neck, has shown to significantly improve treatment outcomes, including higher response rates and prolonged survival.

The mechanism of action for cisplatin's effectiveness includes its ability to enhance DNA damage in tumor cells and inhibit their repair, which leads to better control of the disease when combined with radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiosensitization of advanced squamous cell carcinoma of the head and neck with cisplatin during concomitant radiation therapy. Sharma, VM., Wilson, WR.[2019]

The study found that the prodrug 5'-deoxy-5-fluorouridine (5'-DFUR) combined with radiotherapy produced more than additive antitumor effects against colon cancer in mice, especially with fractionated doses, compared to the standard chemotherapy drug 5-fluorouracil (5-FU) which only showed additive effects.

5'-DFUR demonstrated a better safety profile, causing less damage to normal tissues compared to 5-FU, which resulted in significant toxicity; this suggests that 5'-DFUR may be a more effective and safer option for cancer treatment in combination with radiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative antitumor activity of 5-fluorouracil and 5'-deoxy-5-fluorouridine in combination with radiation therapy in mice bearing colon 26 adenocarcinoma. Ishikawa, T., Tanaka, Y., Ishitsuka, H., et al.[2019]

The study found that (213)Bi immunoconjugates can effectively kill both hypoxic and normoxic CAL33 tumor cells, demonstrating their potential as a treatment for tumors that are resistant to conventional therapies due to low oxygen levels.

Unlike traditional photon radiation, which is less effective on hypoxic cells, the α-particle emitting (213)Bi showed consistent efficacy regardless of the oxygenation status of the tumor cells, making it a promising strategy for targeting hypoxic tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alpha-particle emitting 213Bi-anti-EGFR immunoconjugates eradicate tumor cells independent of oxygenation. Wulbrand, C., Seidl, C., Gaertner, FC., et al.[2021]

The study demonstrated that Diffusing Alpha-emitters Radiation Therapy (DART) effectively retards tumor growth and can lead to tumor eradication in solid squamous cell carcinoma (SCC) tumors in mice, using alpha-emitting radioisotopes from (224)Ra.

DART showed enhanced efficacy when applied to smaller tumors or when using multiple DART wires, suggesting a promising approach for cancer treatment that could be combined with other therapies like chemotherapy or immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Growth retardation and destruction of experimental squamous cell carcinoma by interstitial radioactive wires releasing diffusing alpha-emitting atoms. Cooks, T., Arazi, L., Schmidt, M., et al.[2016]

Citations

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5-Aminolevulinic acid as an emerging radiosensitizer for ... 5‑Aminolevulinic acid (5-ALA) is a keto-carbon amino acid frequently used in glioma surgery for fluorescence-guided resection.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04381806

Phase I Study in Advanced Malignancies With 5-ALA 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 ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0969806X25004025

Application of 5-aminolevulinic acid in cancer radio ... This systematic review aims to provide an overview of the current evidence on RDT using 5-aminolevulinic acid (5-ALA) for the treatment of various cancers.

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5-Aminolevulinic acid as an emerging radiosensitizer for ... 5-Aminolevulinic acid as an emerging radiosensitizer for radiodynamic therapy in solid tumors: a systematic review of available data and clinical potential.

5. withpower.com withpower.com/trial/phase-1-neoplasms-6-2020-14c66

ALA + Radiation for Solid Cancers Trial Overview The study is testing the safety and effectiveness of combining low dose radiation (RT) with a drug called ALA in escalating doses. It aims to ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0303846720307733

5-Aminolevulinic acid radiodynamic therapy for treatment ... RDT uses ionizing radiation to activate radiosensitizers to destroy neoplasms. · 5-ALA enhances the host immune response when combined with ionizing radiation.

7. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2020-06075

Low-dose Radiation and Aminolevulinic Acid for the ... This trial may help doctors learn more about the use of aminolevulinic acid with radiation therapy for the treatment of advanced or metastatic solid tumors.