5-aminolevulinic Acid In Advanced Malignancies

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

This is a phase 1, open label, dose-escalation, safety, pharmacokinetic, and pharmacodynamic study to determine the maximum tolerated doses (MTD) or recommended phase 2 doses (RP2D) of both ALA and RT. Once the MTDs are identified, the cohort providing the highest dose intensity at or below the MTD (if supported by emerging PK and biomarker data) will be selected for an expansion phase for the purpose of refining the safety assessment and assessing preliminary efficacy. The initial dose escalation phase will enroll at least 20 patients across a variety of tumor types, after which concurrent disease site-specific expansion cohorts will accrue, each consisting of 20 patients. Anatomic site-specific cohorts will include patients with symptomatic metastatic disease to specific anatomic regions, where varying toxicity may be expected (Head and Neck, Thorax and Abdomen/Pelvis).

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Drug: Low dose radiation and ALA

• Study Type: Interventional
• Enrollment (Anticipated): 130
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Anthony Olszanski, MD; Phone Number: 2152141676; Email: anthony.olsanski@fccc.edu
• Study Contact Backup: Name: Thomas Galloway, MD; Phone Number: 2157285536; Email: thomas.galloway@fccc.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Recruiting
      • Fox Chase Cancer Center
      • Contact: Anthony Olszanski, MD; Phone Number: 215-214-1676; Email: anthony.olszanski@fccc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Diagnosis:

   1. Patients must have a histologically and/or cytologically confirmed primary solid tumors
   2. Lesion(s) of interest (target or non-target) must be evaluable by PET or MRI
   3. 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 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ALA / Fractions of Radiotherapy; 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.	Drug: Low dose radiation and ALA; Patients will be seen in the CRU and administered ALA on day 1, 8, and 15. Open-field radiotherapy and targeted-field radiotherapy will be given on days 1, 8, and 15; Other Names: Radiation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Max tolerated dose (MTD) of ALA and radiation	Determine the MTD of ALA and radiotherapy when administered concurrently	56 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of adverse events and laboratory abnormalities	Overall safety profile of ALA with RT as characterized by type, frequency, severity, timing and relationship to study therapy of adverse events (AEs) and laboratory abnormalities as per CTCAE v5.0	56 days
Response rate	Objective tumor response, as assessed using the Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1 in patients with measurable disease	1 year

Collaborators and Investigators

• Sponsor: Fox Chase Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): July 30, 2020
• Primary Completion (Anticipated): February 1, 2026
• Study Completion (Anticipated): February 1, 2027

Study Registration Dates

• First Submitted: June 12, 2020
• First Submitted That Met QC Criteria: June 19, 2020
• First Posted (Actual): June 23, 2020

Study Record Updates

• Last Update Posted (Estimate): February 22, 2023
• Last Update Submitted That Met QC Criteria: February 20, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: 20-1009 (Other Identifier: IRB); RT-90 (Other Identifier: FCCC ISRU)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No