X-ray Psoralen Activated Cancer Therapy in Head and Neck, Breast, Sarcoma and Melanoma

Phase 1 Study of X-PACT (X-ray Psoralen Activated Cancer Therapy) for Intra-tumoral Injection of Superficial Tumors in Patients With Advanced Head and Neck Cancer, Breast Cancer, Soft Tissue Sarcoma or Melanoma

In this Phase I trial for subjects with advanced head & neck cancer, breast cancer, soft tissue sarcoma or melanoma all subjects will receive open label X-PACT treatment as a intra-tumoral injection. The primary objective will be to establish the safety of X-PACT when dosed with 5 intra-tumoral injections of the combination product (the phosphor device and methoxsalen sterile solution and subsequently exposing the tumor to X-ray energy) over a period of 6 weeks (on day D1, D3 and D5 of Week 1, on D1 of Week 2, and a booster on D1 of Week 6). After the week 8 tumor assessment subjects demonstrating stable disease, partial response or unconfirmed progression assessed by iRecist, will be eligible to receive two additional booster treatments 4-6 weeks apart. Treatment will be considered safe provided ≤ 2 out of 12 patients experience a dose-limiting toxicity (DLT) during the 6 weeks after the first intra-tumoral injection.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumor Cancer
• Intervention / Treatment: Combination product: X-PACT

Detailed Description

The primary endpoint will be to establish the safety of X-PACT when dosed with 5 intra-tumoral injections of the combination product (the phosphor device and methoxsalen sterile solution and subsequently exposing the tumor to X-ray energy) over a period of 6 weeks (on day D1, D3 and D5 of Week 1, on D1 of Week 2, and a booster on D1 of Week 6). After the week 8 tumor assessment subjects demonstrating stable disease, partial response or unconfirmed progression assessed by iRecist, will be eligible to receive two additional booster treatments 4-6 weeks apart. Treatment will be considered safe provided ≤ 2 out of 12 patients experience a dose-limiting toxicity (DLT) during the 6 weeks after the first intra-tumoral injection. Subjects will have staging scans at baseline, day 8, week 7 and as per standard of care during the optional treatment and follow up study periods. There will be a two-year follow up period.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Susan N McLaughlin, BSN; Phone Number: 7048776363; Email: smclaughlin@immunolight.com
• Study Contact Backup: Name: Lauren Wood, MD; Phone Number: 6788995225

Study Locations

• United States
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Recruiting
      • Levine Cancer Institute
      • Contact: Heather Neagle
      • Contact: Shahab Babakoohi, MD
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University
      • Principal Investigator: Willam Eward, MD
      • Contact: Betsy Sachs
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Recruiting
      • Prisma Health
      • Contact: William J Edenfield, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
2. Age ≥ 18 years at the time of consent
3. ECOG Performance Status of ≤ 1

4. Subjects with histologically or cytologically confirmed advanced solid tumors which have progressed after standard therapy(ies), intolerant to standard therapy, refused standard therapy or for which no standard therapy(ies) exist. Furthermore, the tumor targeted for injections should be:

   1. A non-visceral tumor, a metastatic lymph node, a metastasis from a visceral solid tumor provided the lesion is extravisceral, or a cutaneous tumor. Visceral tumors will not be treated.
   2. The tumor must be measurable as per RECIST criteria.
   3. The tumor should be directly accessible for injection or accessible with the use of ultrasound/CT guidance.
   4. The tumor identified for injection should be selected so local control could potentially provide benefit to the patient.
   5. 80% of the tumor must be accessible for injection with X-PACT (assessed by the treating physician)
   6. The tumor must be superficial and not exceed a depth of 5 cm.
   7. Eye or brain tumors will not be treated.
5. A patient with prior brain metastasis may be considered if they have completed their treatment for brain metastasis at least 4 weeks prior to day 1 of treatment, have been off of corticosteroids for ≥ 2 weeks, and brain metastases are asymptomatic.
6. The study site Radiation Oncologist Investigator/sub-investigator has determined additiional radiation delivered via X-PACT is appropriate given patient's prior radiation exposure. The treating Radiation Oncologist will review all prior radiation received to the proposed site of X-PACT treatment and assess the potential for unacceptable toxicity to the site or local organ(s) using QUANTEC.
7. All toxicities from prior therapy should be ≤Grade 1 before start of study treatment. All radiation associated toxicities must have completely resolved to be considered for inclusion into the study.

8. Demonstrate adequate organ function as defined in the table below:

   Hematological:

   White blood cell (WBC) ≥ 3 x 109/L Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L Platelet Count ≥ 100 x 109/L Hemoglobin (Hgb) ≥ 8 g/dL2

   Renal:

   Serum creatinine OR Creatinine clearance ≤ 1.5 x upper limit of normal (ULN) OR, in patients with a serum creatinine 1.5 x ULN, ≥ 60 mL/min as measured by a 24-hour urine collection or estimated by the Cockcroft and Gault formula

   Hepatic:

   Total bilirubin ≤ 1.5 × ULN (in patients with known Gilbert Syndrome a total bilirubin ≤3.0× ULN with direct bilirubin ≤1.5 X ULN) Aspartate aminotransferase (AST) ≤ 2.5 × ULN (or ≤ 5 if liver metastases are present) Alanine aminotransferase (ALT) ≤ 2.5 × ULN (or ≤ 5 if liver metastases are present)

   Coagulation:

   International Normalized Ratio (INR) ≤ 1.5

9. Females of childbearing potential (FCBP) must have a negative serum pregnancy test within 3 days prior to day 1 of treatment. NOTE: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are postmenopausal (at least 12 consecutive months with no menses without an alternative medical cause).

10. FCBP must be willing to use a highly effective contraceptive method (i.e., achieves a failure rate of <1% per year when used consistently and correctly) from the time of informed consent until 28 days after treatment discontinuation. Contraceptive methods with low user dependency are preferable but not required (see table below, adapted from:

    http://www.hma.eu/fileadmin/dateien/Human_Medicines/01-About_HMA/Working_Groups/CTFG/2014_09_HMA_CTFG_Contraception.pdf)

    Highly Effective Birth Control Methods:

    • combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation

      • oral
      • intravaginal
      • transdermal

    • progestogen-only hormonal contraception associated with inhibition of ovulation

      • oral
      • injectable
      • implantable
    • intrauterine device (IUD)
    • intrauterine hormone-releasing system (IUS)
    • vasectomised partner
    • sexual abstinence
11. Male patients must be willing to use condoms from the time of informed consent until 28 days after treatment discontinuation. For a non-pregnant FCBP partner, contraception recommendations should also be considered.
12. As determined by the enrolling physician, ability of the patient to understand and comply with study procedures for the entire length of the study
13. Patient is expected to have a life expectancy of at least 4 months

14. If the proposed site of treatment with X-PACT had prior exposure to curative-intent radiation, the patient may be entered into the trial with the following provisions satisfied.

    • There is at least a 6 month wash out period from the last date radiation was received to assess for radiation toxicity.
    • If there was previous radiation toxicity at the proposed site of X-PACT, the toxicity resolved at least three months ago and the site did not involve a major organ.
    • The site investigator in addition to the radiation oncologist (as a part of criterion #6) has fully reviewed the subject's radiation history, has examined the area for radiation toxicity and assessed the cumulative dose for either 5 or 7 X-PACT treatments and determined they will not pose additional risk for radiation toxicity or re-activate any other previous toxicity.

Exclusion Criteria:

• Exclusion Criteria:

  1. Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study.)
  2. Prior exposure to methoxsalen

  3. History of any of the following:

     1. Idiosyncratic or hypersensitivity reactions to any psoralen compounds or any of their excipients
     2. Light sensitive disease state
     3. Disease associated with photosensitivity including lupus erythematosus, porphyria cutanea tarda, erythropoietic protoporphyria, variegate porphyria, xeroderma pigmentosum and albinism
     4. Aphakia
  4. History of idiosyncratic or hypersensitivity reactions to any of the phosphor device components
  5. Known diagnosis of human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection (NOTE: testing not required)
  6. Active infection requiring systemic therapy (NOTE: at discretion of investigator, patients with uncomplicated urinary tract infections may be eligible.)
  7. Has a known additional other primary malignancy that is active and/or progressive requiring treatment; exceptions include basal cell skin cancer, in situ cervical or bladder cancer, or other cancer for which the patient has been disease-free for at least five years.
  8. Systemic anti-cancer treatment within 28 days (or 5 half-lives, whichever is shorter) prior to day 1 of treatment
  9. Treatment with any investigational drug within 5 half-lives or 28 days, whichever is shorter (or if half-life is unknown, within 28 days) prior to day 1 of treatment

  10. Impaired cardiac function or clinically significant cardiac diseases, including any of the following:

      1. Uncontrolled cardiac arrhythmia (patients with rate-controlled atrial fibrillation are not excluded)
      2. Uncontrolled hypertension (systolic BP > 170 mmHg or diastolic BP > 105 mmHg at screening) despite two concomitant antihypertensive therapies.
      3. Acute myocardial infarction or unstable angina ≤ 6 months prior to day 1 of treatment
      4. New York Heart Association Class III or IV congestive heart failure (
  11. Other uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements as determined by the investigator.
  12. The tumor identified for treatment has a volume greater than 500 cc (Soft Tissue Sarcoma only). All other tumor types may have a maximum volume of 300 cc
  13. Receiving or planned use of corticosteroids. Subjects will require a one-week washout period from prior corticosteroid use. Inhaled or topical steroids are permitted.
  14. Subjects with active autoimmune disease requiring 10 mg or greater of prednisone and/or biologic agents.
  15. Subjects with a history of pancreatitis or elevated baseline serum lipase without otherwise specified etiology.

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: X-PACT Treatment; Single arm consisting of a six-week treatment period with X-PACT (phosphor device and methoxsalen sterile solution and subsequently exposing the tumor to X-ray energy) administered as an intra-tumoral injection. Intra-tumoral injections will be given on D1, D3 and D5 of Week 1, on D1 of Week 2, and a booster on D1 of Week 6. After the week 8 tumor assessment subjects demonstrating stable disease, partial response or unconfirmed progression assessed by iRecist, will be eligible to receive two additional booster treatments 4-6 weeks apart.

Combination product: X-PACT; X-PACT is comprised of a phosphor device, the drug methoxsalen sterile solution and X-ray energy. The dose of methoxsalen sterile solution per injection will vary per patient and will remained fixed across injections within each patient as it is based on the applicable tumor volume at baseline. Immediately after each injection of the combination product, patients will be exposed to an X-ray beam delivered via a LINAC (and thus targeted at the tumor) at a fixed dose to activate the combination product.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-Limiting Toxicity (DLT)	The primary objective will be to establish the safety of X-PACT when dosed at the schedule described above, with X-PACT considered safe provided ≤ 2 out of 12 patients experience a dose-limiting toxicity (DLT) during the 6 weeks after the first intra-tumoral injection.	First 6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate Local Response Rate (LRR)	Evaluate local response rate by assessing treated tumor volume pre and post treatment	After first 6 weeks of treatment
Evaluate Durability of Response	Evaluate duration of local control	Post first 6 treatments to 2 years post last treatment
Evaluate Objective Response Rate (ORR)	Evaluate the proportion of patients who have a partial or complete response to therapy.	After first 6 weeks of treatment
Evaluate Progression Free Survival	Evaluate the length of time during and after the treatment that the subject lives with the disease but it does not get worse.	Post first 6 treatments to 2 years post last treatment
Evaluate Overall Survival	Evaluate the length of time subjects stay alive from the date of first treatment.	Post first 6 treatments to 2 years post last treatment
PK Profile (C max) of Methoxsalen	Establish C max of methoxsalen when given as an intra-tumoral injection	First 6 weeks of study
PK Profile (AUC) of Methoxsalen	Establish AUC of methoxsalen when given as an intra-tumoral injection	First 6 weeks of study

Collaborators and Investigators

• Sponsor: Immunolight, LLC
• Investigators: Principal Investigator: William Eward, MD, Duke University

Study record dates

Study Major Dates

• Study Start (Actual): December 8, 2021
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: May 4, 2020
• First Submitted That Met QC Criteria: May 11, 2020
• First Posted (Actual): May 15, 2020

Study Record Updates

• Last Update Posted (Actual): February 8, 2024
• Last Update Submitted That Met QC Criteria: February 7, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Advanced Breast Cancer; Advanced Solid Tumor; Advanced Melanoma; Advanced Soft Tissue Sarcoma; Advanced Head & Neck Cancer
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Sarcoma; Melanoma
• Other Study ID Numbers: X-PACT 101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported after deidentification for researchers who provide a methodologically sound proposal.
• IPD Sharing Time Frame: Beginning 6 months after the article publication to 36 months following article publication
• IPD Sharing Access Criteria: Proposals should be directed to smclaughlin@immunolight.com or lwood@immunolight.com. To gain access, data requestors will need to sign a data access agreement. Data are available for 36 months on a third party website.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes