Chemo-Radiotherapy Boost Treatment Guided by Perfusion MRI on Hypoxic Zones in Head and Neck Cancer

PHASE II PROSPECTIVE RANDOMIZED TRIAL OF THE BOOST TREATMENT OF CHEMO-RADIOTHERAPY GUIDED BY PERFUSION MRI IMAGING ON HYPOXIC ZONES IN HEAD AND NECK CANCER

To assess and localize hypoxic tumor subregions both at baseline and during the second week of radiotherapy. And to hypothesize that an intensified IMRT regimen may ensure higher local response rates compared to the standard IMRT approach.

Study Overview

• Status: Active, not recruiting
• Conditions: Squamous Cell Tumors of the Head and Neck
• Intervention / Treatment: Drug: Cisplatin IV on days 1, 22, 43, at a dose of 100 mg/m2

Detailed Description

A randomized, prospective, phase II study conducted with the aim of evaluating whether the strategy of overdosing hypoxic sub-regions of the primary tumor is associated with better local control compared to standard chemoradiotherapy for squamous cell carcinomas of the head and neck.

To evaluate whether side effects are influenced by the MRT approach. To search for initial (pre-treatment) hypoxic regions during treatment (at the 10th fraction of RT) in terms of volume and location. And finally to determine the prevalence and importance of pre-treatment hypoxic sub-regions and correlate the results with both clinical (primary site and tumor volume) and pathological (VEGF, EGFR and HIF-α expression in the primary tumor) characteristics.

• Study Type: Interventional
• Enrollment (Estimated): 91
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Roma, Italy, 00144
    • IRCSS Regina Elena
  • Rome, Italy, 00144
    • "Regina Elena" National Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• histologically confirmed squamous cell carcinoma of the oropharynx, hypopharynx, or larynx;
• AJCC stage III or IV (cT2-4 N0-3 M0);
• specific informed consent.

Exclusion Criteria:

• Documented allergy to radiological contrast media or inability to receive contrast media due to concomitant pathology (e.g. renal);
• inability to receive radiotherapy (e.g. previous radiotherapy in the same region) and/or chemotherapy (inadequate bone marrow and/or liver and/or renal function);
• incomplete acquisition of MRI images;
• performance status 2 or more according to Zubrod;
• Previous invasive neoplasm (except skin cancer), except for neoplasms controlled for at least three years; non-invasive tumors (e.g. carcinoma in situ of the breast) are admitted even if diagnosed and treated in a period less than 3 years prior; patients with simultaneous or bilateral primary tumors are excluded;
• alcohol or drug abuse;
• legal incapacity or limited legal capacity;
• concomitant treatment with investigational drugs or participation in another clinical trial with use of investigational drugs within 30 days prior to screening for the study;
• documented hypersensitivity to study drugs or any of their excipients;
• pregnancy and/or breastfeeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: stIMRT standard IMRT regimen; In this treatment arm, chemoradiotherapy will be administered at doses of 70 Gy, 63 Gy and 58.1 Gy will be administered to PTV1, PTV2 and PTV3 respectively in 35 fractions (5 fractions per week) with simultaneous integrated boost (SIB) technique. Chemotherapy will consist of i.v. cisplatin on days 1, 22, 43, at a dose of 100 mg/m2. Hydration and antiemetics are controlled according to the Institute guidelines.	Drug: Cisplatin IV on days 1, 22, 43, at a dose of 100 mg/m2; Chemoradiotherapy will be performed from day 1 to day 49 regardless of the arm.; Other Names: Radioterapia 70 Gy, 63 Gy e 58.1 Gy
Experimental: deIMRT intensified IMRT regimen; In the IMRT arm, the baseline HV dose (HV1) is further increased by 10% up to 77 Gy in 35 fractions (5 fractions per week) using SIB technique (2.2 Gy/fraction). Once the MR2 is performed at the 10th fraction, the hypoxic volumes (HV2) will be re-estimated and coregistered with the initial planning CT, if the HV2 is within the HV1, no change will be applied; if new hypoxic volumes are identified outside the initial HV1 volume, the plan will be adapted to boost these regions as well. Chemotherapy will consist of i.v. cisplatin on days 1, 22, 43, at a dose of 100 mg/m2. Hydration and antiemetics are controlled according to the Institute guidelines.	Drug: Cisplatin IV on days 1, 22, 43, at a dose of 100 mg/m2; Chemoradiotherapy will be performed from day 1 to day 49 regardless of the arm.; Other Names: Radioterapia 70 Gy, 63 Gy e 58.1 Gy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response	Complete response is defined as complete disappearance (100%) of tumor at any site (primary and nodal) on both physical examination and imaging. Any site (primary or nodal) suspicious for residual disease on re-evaluation imaging or physical examination will be confirmed by pathology	2 years

Collaborators and Investigators

• Sponsor: Regina Elena Cancer Institute
• Investigators: Study Director: Giuseppe Sanguineti, Doctor, IRCCS National Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): September 16, 2020
• Primary Completion (Actual): July 31, 2024
• Study Completion (Estimated): July 31, 2027

Study Registration Dates

• First Submitted: March 11, 2025
• First Submitted That Met QC Criteria: March 11, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 11, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Antineoplastic Agents; Cisplatin
• Other Study ID Numbers: RS1308/20

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No