LAttice Radiation Therapy for Large Lesions: Reggio Emilia Single-arm Phase II Trial

LAttice Radiation Therapy for Large Lesions: Reggio Emilia Single-arm Phase II Trial (LART Trial)

This study evaluates the activity and toxicity of Lattice Radiation Therapy (LRT) in patients with large, unresectable non-brain neoplastic lesions requiring palliative treatment. Eligible patients will 5 fractions LRT, delivered in every other day, to 20 Gy with a simultaneous boost to a minimum median dose of 50 Gy. No concomitant antineoplastic drugs will be allowed. Patients will be followed at 14, 30, 60, and 90 days after treatment, then every 3 months up to 1 year. Tumor response will be assessed using objective response rate (ORR) per RECIST 1.1, with CT scans at 3, 6, 9, and 12 months. Secondary endpoints include local control, toxicity (CTCAE v.5.0), and patient-reported outcomes (PROMs) to assess their quality of life (EORTC QLQ-C15-PAL and PRO-CTCAE). Exploratory objectives will assess the immunomodulatory effects of LRT through immune cell characterization and quantification of immune-related circulating factors before and after treatment.

Inclusion Criteria:

• Age ≥18 on day signing informed consent
• Histologically or cytologically confirmed cancer.
• Performance status of 0-2 on the ECOG Performance Scale.
• Advanced or locally advanced disease, not eligible for curative-intent treatment.
• Life expectancy > 6 months.
• At least one measurable non-brain site of disease with a diameter ≥ 4.5 cm, in any direction
• Ability to understand and willingness to sign the written informed consent document (or that of legally authorized representative, if applicable).

Reproductive Status

• Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of LRT.
• Women must not be breastfeeding.
• WOCBP must agree to follow instructions for method(s) of contraception for the duration of LRT plus 30 days (duration of ovulatory cycle).
• Men who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of LRT plus 90 days (duration of sperm turnover).
• Investigators shall counsel WOCBP patients and male patients who are sexually active with WOCBP on the importance of pregnancy prevention and the implications of an unexpected pregnancy

Exclusion Criteria:

• Additional malignancy that is progressing or requires active treatment. Exceptions include basal and squamous cell carcinoma of the skin or in situ cervical
• Currently participating in or has participated in a study of an investigational agent or using an investigational device within 2 weeks of the start of LRT.
• Prior high-dose radiotherapy overlapping with any planned site of protocol radiotherapy, if the dose overlap is > 10 Gy or is determined not safe by the treating physician.
• HIV patients with CD4+ T-cell counts < 350 cells/mcL or with a history of AIDS-defining opportunistic infection, within the 12 months prior to registration