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Head & Neck Squamous Cell CarcinomaPhase 1/2NCT07920289

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

A Phase 1/2 study testing Addition of Promitil to External Beam Radiotherapy in people with Head & Neck Squamous Cell Carcinoma and Locally Advanced Head and Neck Squamous Cell Carcinoma, run by Assuta Ashdod Hospital.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial summary

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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Addition of Promitil to External Beam Radiotherapy
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
No sites listed yet
Study dates
30 Oct 2026to 30 May 2033
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • Known hypersensitivity to the study drug or to any of its components
  • Chronic liver disease or cirrhosis with Child-Pugh Class C score
  • Any other severe concurrent disease which in the judgment of the investigator would make the patient unsuitable for entry into this study
  • History of human immunodeficiency virus (HIV) infection
  • 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
  • Presence of uncontrolled infection
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  • Evidence of active bleeding or bleeding diathesis
  • Pregnant or lactating
  • 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)

Trial locations and contacts

No sites are listed yet. Contact the study team or a site near you to ask about taking part.

Vered Vazana contact

+972508319523

veredvaz@ashmc.co.il

About this study

Official title: 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.

Read the detailed description

This will be an open-label, single-arm, prospective study, in which up to 20 adult patients requiring RT for locally and/or regionally advanced head and neck (HN) cancers will undergo a combination treatment of intravenously (IV) delivered PROMITIL and standard of care RT. The treatment regimen will involve administration of 3 PROMITIL doses (2 mg/kg body weight (BW)), delivered at 21-day intervals. In parallel, a course of external beam RT (EBR) will be 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. Five sentinel patients (the first 5 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 throughout the three 21-day treatment courses (43 days total) and, then again 4 weeks after the last RT treatment.

All AEs will be logged for the first 20 weeks of the study. Thereafter, only serious adverse events (SAEs), adverse events of special interest (AESI), new malignancies, death of any cause and pregnancy outcomes will be logged until the end of the long term surveillance period. PROMITL treatment will be discontinued in patients with intolerable toxicity to the combination treatment.

Disease status will be reevaluated 28 days (±7 days) from the end of the last RT treatment fraction by a direct clinical examination. PET-CT or CT will be conducted 12 weeks (±7 days) from the end of RT treatment fraction. 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. No other anticancer treatments will be allowed during the treatment period and throughout the follow-up period. Patients with recurrent disease will be withdrawn from the study but followed-up for up to 60 months for survival.

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.

Being tested
Addition of Promitil to External Beam Radiotherapy
Keywords
Cisplatin ineligible, External Beam Radiotherapy, Head and Neck Squamous Cell Carcinoma, Liposomal Prodrug for Mitomicin C, Promitil
Medical subject headings
Squamous Cell Carcinoma of Head and Neck

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Addition of Promitil to External Beam RadiotherapyDrug

    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.

Study groups in NCT07920289
Study groupRoleWhat they receive
Single Interventional Arm of Promitil Combined With RadiotherapyExperimentalThe 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.
Receives: Drug: Addition of Promitil to External Beam Radiotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Short and Intermediate-Term Safety

    To evaluate the short- and intermediate-term safety of PROMITIL in combination with EBR in an adult population with locally or regionally advanced head and neck cancer and to clear a safe dose level for phase 3 studies

    Measured: Two Years

  2. 2-year event-free survival (EFS)

    To evaluate the 2-year event-free survival (EFS) rate in patients treated with PROMITIL in combination with EBR from the day of the first RT treatment fraction

    Measured: Two years

Secondary outcomes (6)

  1. Long-Term Safety of PROMITIL

    To evaluate the long-term safety of PROMITIL in combination with EBR in an adult population with locally or regionally advanced head and neck advanced cancer

    Measured: Five Years

  2. Local-Regional Recurrence-Free Survival (LRFS)

    To evaluate local-regional recurrence-free survival (LRFS) (in months) from the day of the first RT treatment fraction.

    Measured: Five Years

  3. Distant Metastasis-Free Survival (DMFS)

    To evaluate distant metastasis-free survival (DMFS) (in months) from the day of the first RT treatment fraction.

    Measured: Sixty Months

  4. Time to Recurrence (TTR)

    To evaluate time to recurrence (TTR) (in months) from the day of the first RT treatment fraction.

    Measured: 60 months

  5. Overall Survival (OS)

    To evaluate overall survival (OS) (in months) from the day of the first RT treatment fraction.

    Measured: Sixty Months

  6. Overall Response Rate (ORR)

    To evaluate the overall response rate (ORR) to PROMITIL in combination with EBR

    Measured: Sixty Months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Nov 2026
  2. Study start30 Oct 2026 (estimated)
  3. Primary completion30 May 2028 (estimated)
  4. Study completion30 May 2033 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07920289
Sponsor's protocol ID
LIPORAD-2
Status last verified
Nov 2026
First submitted
29 Oct 2026
Last updated
5 Nov 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Tian X, Warner SB, Wagner KT, Caster JM, Zhang T, Ohana P, Gabizon AA, Wang AZ. Preclinical Evaluation of Promitil, a Radiation-Responsive Liposomal Formulation of Mitomycin C Prodrug, in Chemoradiotherapy. Int J Radiat Oncol Biol Phys. 2016 Nov 1;96(3):547-55. doi: 10.1016/j.ijrobp.2016.06.2457. Epub 2016 Jul 1.

    PubMed 27681751

  • Sapir E, Pfeffer R, Wygoda M, Purim O, Levy A, Corn B, Amitay Y, Ohana P, Gabizon A. Pegylated Liposomal Mitomycin C Lipidic Prodrug in Combination With External Beam Radiation Therapy in Patients With Advanced Cancer: A Phase 1B Study. Int J Radiat Oncol Biol Phys. 2023 Sep 1;117(1):64-73. doi: 10.1016/j.ijrobp.2023.03.046. Epub 2023 Mar 17.

    PubMed 36933845

  • Gabizon A, Shmeeda H, Tahover E, Kornev G, Patil Y, Amitay Y, Ohana P, Sapir E, Zalipsky S. Development of Promitil(R), a lipidic prodrug of mitomycin c in PEGylated liposomes: From bench to bedside. Adv Drug Deliv Rev. 2020;154-155:13-26. doi: 10.1016/j.addr.2020.07.027. Epub 2020 Aug 7.

    PubMed 32777239

  • Gabizon AA, Tzemach D, Horowitz AT, Shmeeda H, Yeh J, Zalipsky S. Reduced toxicity and superior therapeutic activity of a mitomycin C lipid-based prodrug incorporated in pegylated liposomes. Clin Cancer Res. 2006 Mar 15;12(6):1913-20. doi: 10.1158/1078-0432.CCR-05-1547.

    PubMed 16551877

  • Bulbake U, Doppalapudi S, Kommineni N, Khan W. Liposomal Formulations in Clinical Use: An Updated Review. Pharmaceutics. 2017 Mar 27;9(2):12. doi: 10.3390/pharmaceutics9020012.

    PubMed 28346375

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Addition of Promitil to External Beam Radiotherapy in people with Head & Neck Squamous Cell Carcinoma and Locally Advanced Head and Neck Squamous Cell Carcinoma, run by Assuta Ashdod Hospital.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 5 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Vered Vazana (+972508319523, veredvaz@ashmc.co.il), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Short and Intermediate-Term Safety (time frame: Two Years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07920289, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2026.

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