Using 5-ALA and low-dose radiation to treat advanced solid tumors

A Phase I Dose Finding Study Of Low-dose Radiation With Sensitization Using 5-aminolevulinic Acid In Advanced Malignancies

This study is testing if a new treatment using 5-ALA and lower doses of radiation can help people with advanced solid tumors that haven't responded to regular therapies.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 130 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Fox Chase Cancer Center (Academic / other)
• Drugs / interventions: radiation
• Locations: 1 site (Philadelphia, Pennsylvania)
• Trial ID: NCT04381806 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the use of 5-ALA in combination with lower doses of radiation therapy to treat advanced solid tumors. The approach aims to selectively target cancerous lesions while minimizing damage to surrounding healthy tissues, similar to photodynamic therapy. Patients with advanced malignancies that are resistant to standard treatments will be evaluated for their response to this novel therapy. The study is based on preliminary data suggesting safety and tolerability, with some patients showing marked responses to treatment.

Who should consider this trial

Good fit: Ideal candidates are patients with histologically confirmed advanced solid tumors that are resistant to standard therapies and who can undergo PET or MRI imaging.

Not a fit: Patients with non-solid tumors or those who are unable to undergo PET/MRI imaging will not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a safer and more effective option for patients with advanced solid tumors that have not responded to conventional therapies.

How similar studies have performed: Similar approaches have shown promise in other settings, but this specific combination of therapies has not been formally tested in a clinical trial before.

Eligibility criteria

Inclusion Criteria

1. Diagnosis:

   a. Patients must have a histologically and/or cytologically confirmed primary solid tumors b. Lesion(s) of interest (target or non-target) must be evaluable by PET or MRI c. Radiographic or clinical evidence of advanced/metastatic disease that is: i. Resistant to standard therapy or for which no standard therapy is available.
2. Patient must be a candidate for, and be willing to undergo, PET/MRI imaging

   1. Patients who refuse MRI imaging are not eligible
   2. Patients who cannot undergo PET/MRI imaging will be deemed screen failures. Rescreening X1 (once) is permissible if the investigator feels that appropriate premedications may allow successful imaging.
3. All previous therapies for cancer, including radiotherapy, major surgery, and/or investigational therapies, must be discontinued for ≥ 14 days (≥ 28 days for mitomycin C or nitrosoureas ) before the treatment date, and all acute effects of any prior therapy must have resolved to baseline severity or Grade ≤ 1 Common Terminology Criteria for Adverse Events (CTCAE v5), except alopecia or parameters defined in this eligibility list

   a. Patients previously treated with a bleomycin regimen are not permitted to undergo radiation therapy to the thorax
4. Age ≥ 18 years
5. ECOG performance status ≤ 2
6. Systolic blood pressure ≥ 110 mmHg and diastolic blood pressure ≥ 70 mmHg
7. Adequate organ and marrow function as defined below:

   1. Absolute neutrophil Count ≥1,000/mm3 without growth factor use ≤ 7 days prior to C1D1
   2. Platelets ≥75,000/mm3 without platelet transfusion ≤ 7 days prior to C1D1
   3. Hemoglobin \>8.0 mg/dL without red blood cell transfusion ≤ 7 days prior to C1D1
   4. Total serum bilirubin \<1.5 X upper limit of normal (ULN)
   5. AST (SGOT)/ALT (SGPT) ≤2 X ULN
   6. Serum creatinine ≤ 1.5 X ULN AND Creatinine clearance (per eGFR) ≥ 40 mL/min/1.73 m2)
8. Serum or urine pregnancy test (for females of childbearing potential) negative within ≤7 days of C1D1
9. Ability to understand and the willingness to sign a written informed consent document and comply with the study scheduled visits, treatment plans, laboratory tests and other procedures.
10. Female patients must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the period of the trial and for at least 90 days after completion of treatment. Male patients must be surgically sterile or must agree to use effective contraception during the period of the trial and for at least 90 days after completion of treatment. The decision of effective contraception will be based on the judgment of the principal investigator or a designated associate.

Exclusion Criteria

1. Patients with symptomatic brain metastases are excluded. Patients with asymptomatic and treated CNS metastases may participate in this trial. The patient must have completed any prior treatment for CNS metastases ≥ 28 days prior to study entry, including radiotherapy or surgery. Steroids for the treatment of symptoms of brain metastasis are not permitted.
2. Patients must be able to take enterally-administered medications. Patients must not have any clinical evidence of impaired gastrointestinal function or any gastrointestinal disease that may significantly alter the absorption of ALA, in the opinion of the treating investigator. Patients who cannot swallow but rely on enterally-administered supplementation may enroll if they otherwise meet this criterion.
3. Current active treatment in another therapeutic clinical study
4. Active bacterial, fungal or viral infection, including hepatitis B (HBV) or hepatitis C (HCV) , requiring treatment with intravenous antibiotic, anti-fungal, or anti-viral medications (testing is not required for eligibility).

   a. Patients may be enrolled while undergoing treatment for trivial infections with oral agents (e.g. superficial skin infections, uncomplicated urinary tract infections, candidal oral/vaginal infections, conjunctivitis, etc)
5. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)- related illness (testing is not required for eligibility)
6. Patients undergoing phototherapy for another, non-oncologic or oncologic disease (e.g. PUVA therapy or photodynamic therapy for skin diseases)
7. Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack or symptomatic pulmonary embolism.
8. Patients with a known history of porphyria (testing for porphyria is not required to participate).
9. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, or in the judgment of the investigator would make the patient inappropriate for entry into the study.
10. 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.
11. Pregnant or breast-feeding patients

Where this trial is running

Philadelphia, Pennsylvania

• Fox Chase Cancer Center — Philadelphia, Pennsylvania, United States (Recruiting)

Study contacts

• Study coordinator: Anthony Olszanski

Conditions Solid Tumor