Intravenously Administered PROMITIL Combined With Radiotherapy in Patients With Cisplatin-Ineligible Head and Neck Cancer Patients

Trial details

Who runs it

Assuta Ashdod Hospital

Trial code

NCT07920289

Record updated

2026. november 5.

Original description

This will be an open-label, single-arm, prospective study, in which patients requiring RT for locally and/or regionally advanced head and neck cancers will undergo a combination treatment comprised of intravenously delivered PROMITIL and standard-of-care radiotherapy (RT). The treatment regimen will involve administration of 3 PROMITIL doses, delivered at 21-day intervals, and a course of external beam radiotherapy (EBR), initiated 1-3 days after the first PROMITIL dose. EBR will consist of either standard daily fractionation (5 per week) of up to a total of 70 Gy at 2 Gy/fraction (7 weeks) or a hypofractionated regimen of up to 55 Gy at 2.75 Gy/fraction (HYPNO regimen; 4 weeks), per investigator's preference. PROMITIL will be given by intravenous infusion at a dose of 2 mg/kg body weight with a capped maximal dose of 150 mg. Five sentinel patients (the first five enrolled patients) will be treated with a dose of 1.8 mg/kg body weight for the purpose of conducting a safety analysis to determine tolerability of the dosing regimen prior to enrolling the remaining study patients. Treatment safety will be assessed on a weekly basis, as well as 4 weeks after the last RT treatment. Disease status will be reevaluated 28 days (±7 days) from the end of last radiation treatment by a direct clinical examination. PET CT or CT will be conducted 12 weeks (±7 days) from the end of RT treatment. Thereafter, PET CT and/or CT scans will be repeated every 6 months for the first 24 months, followed by yearly imaging. In addition, during the follow-up phase, the patient will be assessed by a radiation oncologist and/or ENT specialist every 3 months during the first year, every 4 months during the second and third years and every 6 months in years 4 and 5 of observation. A first interim analysis will be conducted 3 months after end of treatment to evaluate safety and response rate. A second interim analysis will be conducted 2 years after end of treatment to evaluate event-free survival (EFS) and delayed toxicities. Final analysis of long-term disease control and survival will be conducted after 5 years.Read full original descriptionShow less

An Open-label, Phase IB/IIA Single-Arm Trial of Intravenously Administered Pegylated Liposomal Mitomycin C Lipid-based Prodrug (PROMITIL) in Combination With External Beam Radiotherapy in Patients With Cisplatin-Ineligible Head and Neck Cancer Patients ("LIPORAD- 2")

This will be an open-label, single-arm, prospective study, in which patients requiring RT for locally and/or regionally advanced head and neck cancers will undergo a combination treatment comprised of intravenously delivered PROMITIL and standard-of-care radiotherapy (RT). The treatment regimen will involve administration of 3 PROMITIL doses, delivered at 21-day intervals, and a course of external beam radiotherapy (EBR), initiated 1-3 days after the first PROMITIL dose. EBR will consist of either standard daily fractionation (5 per week) of up to a total of 70 Gy at 2 Gy/fraction (7 weeks) or a hypofractionated regimen of up to 55 Gy at 2.75 Gy/fraction (HYPNO regimen; 4 weeks), per investigator's preference. PROMITIL will be given by intravenous infusion at a dose of 2 mg/kg body weight with a capped maximal dose of 150 mg. Five sentinel patients (the first five enrolled patients) will be treated with a dose of 1.8 mg/kg body weight for the purpose of conducting a safety analysis to determine tolerability of the dosing regimen prior to enrolling the remaining study patients. Treatment safety will be assessed on a weekly basis, as well as 4 weeks after the last RT treatment. Disease status will be reevaluated 28 days (±7 days) from the end of last radiation treatment by a direct clinical examination. PET CT or CT will be conducted 12 weeks (±7 days) from the end of RT treatment. Thereafter, PET CT and/or CT scans will be repeated every 6 months for the first 24 months, followed by yearly imaging. In addition, during the follow-up phase, the patient will be assessed by a radiation oncologist and/or ENT specialist every 3 months during the first year, every 4 months during the second and third years and every 6 months in years 4 and 5 of observation. A first interim analysis will be conducted 3 months after end of treatment to evaluate safety and response rate. A second interim analysis will be conducted 2 years after end of treatment to evaluate event-free survival (EFS) and delayed toxicities. Final analysis of long-term disease control and survival will be conducted after 5 years.

Inclusion: Pathologically or cytologically confirmed diagnosis of locally and/or regionally advanced stage III-IV HNSCC (laryngeal, hypopharyngeal, oropharyngeal, maxillary sinus and oral cavity cancers); Cisplatin-ineligible patients, defined as those meeting one or more of the following criteria:; Renal impairment; Creatinine clearance < 50mL/min; Chronic kidney disease stage 3b-5; Hearing loss/ototoxicity; Pre-existing grade ≥ 2 sensorineural hearing loss or tinnitus; Neuropathy; Pre-existing grade ≥ 2 peripheral neuropathy; Poor general condition on clinical examination; Other comorbidities; Uncontrolled cardiovascular disease (heart failure, recent myocardial infarction, unstable angina); Age/frailty • Age ≥75 years or frail patients with multiple comorbidities where cisplatin toxicity is unacceptable; No prior radiotherapy to the target anatomic site; Age ≥18 years; BMI: 18-36 kg/m2; ECOG performance status ≤ 2; Estimated life expectancy of > 12 months; Adequate bone marrow function (an absolute neutrophil count ≥1500/mm3, hemoglobin ≥9.5 g/dl, and a platelet count ≥100,000/mm3); Adequate liver function (serum bilirubin ≤2.0 mg/100 ml; alanine aminotransferase ≤3× upper limit of normal (ULN), albumin ≥34 g/L); Women of child-bearing potential practicing an acceptable method of birth control; Understanding of study procedures and willingness to comply for the entire length of the study and to provide written informed consent.

Exclusion: Any other severe concurrent disease which in the judgment of the investigator would make the patient unsuitable for entry into this study; Prior intravenous treatment with MMC, either alone or in combination; Patients received any type of systemic therapy for their HNSCC prior to the beginning of radiation therapy (e.g., neoadjuvant or induction chemotherapy or immunotherapy); Known hypersensitivity to the study drug or to any of its components; Chronic liver disease or cirrhosis with Child-Pugh Class C score; History of human immunodeficiency virus (HIV) infection; Presence of uncontrolled infection; Evidence of active bleeding or bleeding diathesis; History of chronic active hepatitis including patients who are carriers of hepatitis B virus (HBV) or hepatitis C virus (HCV), unless adequately treated and shown to be serum virus-free; Pregnant or lactating.

ClinicalTrials.gov NCT07920289