X-PACT for Advanced Cancers

Recruiting at 4 trial locations

Overseen By Lauren Wood, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Immunolight, LLC

Must not be taking: Corticosteroids, Biologics

Disqualifiers: Pregnancy, HIV, Hepatitis, others

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

Compensation: Varies

Number of Visits: 13

Duration: 6 weeks

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety of a new treatment called X-PACT (X-Ray Psoralen Activated Cancer Therapy) for individuals with certain advanced cancers, such as head and neck cancer, breast cancer, soft tissue sarcoma, or melanoma. The treatment involves injecting a combination of a phosphor device and a methoxsalen solution directly into the tumor, followed by exposure to X-ray energy. Ideal participants have specific types of advanced tumors accessible by injection and have not found success with other standard therapies. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive this innovative therapy.

Do I have to stop taking my current medications for the trial?

The trial requires a one-week period without corticosteroids before starting, and you must not have had systemic anti-cancer treatment within 28 days before the trial. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

What prior data suggests that the X-PACT treatment is safe for advanced cancers?

Research shows that X-PACT, a new cancer treatment, is generally well-tolerated. It uses low doses of X-rays to target tumors, protecting the surrounding healthy tissue. Earlier studies aimed these low-dose X-rays directly at tumors, and the treatment did not cause severe side effects.

However, since this trial is in its early stages, the researchers are still assessing its safety. The aim is to ensure that no more than 2 out of 12 patients experience serious side effects during the initial treatment period. This trial will help confirm if X-PACT is safe for more patients in the future. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for advanced cancers, which often involve chemotherapy or radiation, X-PACT is unique because it combines a phosphor device and a methoxsalen sterile solution with X-ray energy, targeting tumors directly via intra-tumoral injections. This innovative approach allows the treatment to act precisely on cancer cells, potentially reducing harm to surrounding healthy tissues. Researchers are excited about X-PACT because it offers a new mechanism of action that could result in effective tumor control with fewer side effects and an improved quality of life for patients.

What evidence suggests that X-PACT is effective for advanced cancers?

Research suggests that X-PACT therapy, which participants in this trial will receive, might reduce cancer severity. This treatment uses special substances called psoralens, which can fight tumors, and activates them with X-ray energy. In lab studies, X-PACT caused more cancer cell death and damage than using psoralens or X-rays alone. Additionally, X-PACT treatment resulted in lower levels of certain proteins linked to cancer severity. These early findings indicate that X-PACT could effectively combat advanced cancers. ^{1 3 4 6 7}

Who Is on the Research Team?

William Eward, DVM, MD

Principal Investigator

Duke University

Are You a Good Fit for This Trial?

Adults over 18 with advanced head & neck cancer, breast cancer, soft tissue sarcoma or melanoma can join this trial if their tumor is superficial (less than 5 cm deep), measurable by RECIST criteria, and accessible for injection. They must have an ECOG Performance Status of ≤1, adequate organ function, no severe allergies to psoralen compounds or the phosphor device components, not be pregnant/breastfeeding and agree to use effective contraception.

Inclusion Criteria

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.

My tumor can be reached for treatment either directly or with imaging guidance.

My side effects from previous treatments are mild or gone.

Exclusion Criteria

I haven't had any cancer treatments in the last 28 days or 5 half-lives, whichever is shorter.

I have a history of pancreatitis or high levels of lipase in my blood without a known cause.

I have another cancer besides the one being studied, but it's either not active or is a minor type that doesn't require treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive X-PACT treatment as intra-tumoral injections over a period of 6 weeks

6 weeks

5 visits (in-person) on D1, D3, D5 of Week 1, D1 of Week 2, and D1 of Week 6

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Staging scans at baseline, day 8, week 7, and as per standard of care

Optional Booster Treatment

Eligible participants receive two additional booster treatments 4-6 weeks apart

4-6 weeks

Open-label Extension

Participants who respond to treatment may receive an additional 12 treatments over 12 months

12 months

What Are the Treatments Tested in This Trial?

Interventions

• X-PACT

Trial Overview The X-PACT treatment involves injecting a combination product into the tumor and exposing it to X-ray energy. This Phase I trial aims to establish safety through five injections over six weeks. Patients showing stable disease or response may receive two additional boosters. Safety will be determined if ≤2 out of 12 patients experience dose-limiting toxicity post-treatment.

How Is the Trial Designed?

Group I: X-PACT Treatment Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Immunolight, LLC

Lead Sponsor

Trials

2

Recruited

20+

Published Research Related to This Trial

The R2Pulm trial found no significant difference in event-free or overall survival between patients with Ewing sarcoma treated with high-dose busulfan-melphalan chemotherapy and those receiving standard chemotherapy with whole-lung irradiation, indicating similar efficacy.

However, the BuMel treatment was associated with higher rates of severe acute toxicities, including four deaths related to treatment, suggesting that the standard VAI plus WLI approach may be safer for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Dose Chemotherapy Compared With Standard Chemotherapy and Lung Radiation in Ewing Sarcoma With Pulmonary Metastases: Results of the European Ewing Tumour Working Initiative of National Groups, 99 Trial and EWING 2008. Dirksen, U., Brennan, B., Le Deley, MC., et al.[2022]

A high tumor engraftment rate of 77.8% was achieved using two methods (subcutaneous and subrenal capsule) to establish patient-derived tumor xenograft (PDTX) models from 18 high-risk endometrial cancer patients, providing a robust platform for drug evaluation.

The study confirmed that the PDTX tumors closely resemble the primary tumors in terms of histology and genetic profiles, making them valuable for personalized medicine strategies and biomarker identification in high-risk endometrial cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Establishment of Patient-Derived Tumor Xenograft Models of High-Risk Endometrial Cancer. Zhu, M., Jia, N., Nie, Y., et al.[2019]

The study established five patient-derived xenograft (PDX) models of nasopharyngeal carcinoma (NPC) and identified significant genetic alterations, including cyclin D1 amplification and CDKN2A deletion, which are potential targets for personalized cancer therapy.

Palbociclib, a cyclin-dependent kinase inhibitor, demonstrated anti-tumor effects in NPC PDX models and showed promise in a patient with liver metastasis, leading to stable disease and a reduction in Epstein-Barr virus (EBV) levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integrated genomic analyses in PDX model reveal a cyclin-dependent kinase inhibitor Palbociclib as a novel candidate drug for nasopharyngeal carcinoma. Hsu, CL., Lui, KW., Chi, LM., et al.[2022]

In a study involving 30 patient-derived xenografts (PDXs) from pediatric tumors, a successful engraftment rate of 44% was observed, with factors like age over 12 years and relapsed disease linked to higher rates of engraftment.

PDX engraftment from newly diagnosed patients was found to be a significant prognostic factor for poor outcomes, particularly in standard-risk Ewing sarcoma, indicating that successful PDX models may predict a higher risk of relapse or refractory disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic value of patient-derived xenograft engraftment in pediatric sarcomas. Castillo-Ecija, H., Pascual-Pasto, G., Perez-Jaume, S., et al.[2023]

In a study of 107 patients with recurrent Ewing sarcoma, the 5-year post-relapse survival rate was found to be only 19%, highlighting the challenges in treating this aggressive cancer after relapse.

Factors such as being younger than 15 years, having a longer time to recurrence (over 24 months), and recurrence limited to the lungs were associated with better post-relapse survival, while no survival benefit was observed from high-dose chemotherapy consolidation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-relapse survival in patients with Ewing sarcoma. Ferrari, S., Luksch, R., Hall, KS., et al.[2022]

Citations

1. journals.plos.org journals.plos.org/plosone/article?id=10.1371/journal.pone.0162078

X-Ray Psoralen Activated Cancer Therapy (X-PACT) The data suggests the possibility of a slightly greater effect at 80 kVp. X-PACT therapy seeks to engage the anti-tumor properties of psoralens ...

2. aacrjournals.org aacrjournals.org/cancerres/article/84/6_Supplement/6642/735198/Abstract-6642-Exploring-the-x-ray-psoralen

Abstract 6642: Exploring the x-ray psoralen activated cancer ... Together, the lower concentrations of G-CSF, Eotaxin, TIMP1, and IL-1β suggest a softening of cancer severity following X-PACT treatment.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04389281

X-ray Psoralen Activated Cancer Therapy in Head and ... 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 ...

4. dukespace.lib.duke.edu dukespace.lib.duke.edu/items/e5dec34a-2639-4f4a-bb8b-cb2b0c990db8

X-Ray Psoralen Activated Cancer Therapy (X-PACT). In an in-vitro study, we show that X-PACT induces significant tumor cell apoptosis and cytotoxicity, unlike psoralen or phosphor alone (p<0.0001). We also show ...

5. researchgate.net researchgate.net/publication/307577127_X-ray_psoralen_activated_cancer_therapy_X-PACT

(PDF) X-ray psoralen activated cancer therapy (X-PACT) PDF | This work investigates X-PACT (X-ray Psoralen Activated Cancer Therapy): a new approach for the treatment of solid cancer.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/27583569/

X-Ray Psoralen Activated Cancer Therapy (X-PACT) In summary, X-PACT represents a novel treatment approach in which well-tolerated low doses of x-ray radiation are delivered to a specific tumor ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10942908/

Psoralen: a narrative review of current and future ... X-PACT (X-ray Psoralen Activated Cancer Therapy) exemplifies this by using uses low-dose X-rays (about 1 Gy) to activate inorganic phosphor ...