Randomized Phase II Study of DCE-MRI-based Dose Escalation for Poor-prognosis and Neck Cancer

This study aims to improve locoregional control of poor prognosis Head and Neck Cancer (HNC) patients by selectively escalating the radiotherapy dose to subvolumes of tumor likely to be resistant to standard Radiation Therapy (RT) using DCE-MRI (Dynamic Contrast Enhanced Magnetic Resonance Imaging). Standard doses of radiotherapy to the rest of the tissues and surrounding normal tissues will be maintained.

Study Overview

• Status: Completed
• Conditions: Squamous Cell Carcinoma of the Head and Neck
• Intervention / Treatment: Radiation: IMRT (Intensity-Modulated Radiation Therapy); Drug: Cisplatin; Drug: Carboplatin; Radiation: Boost Radiation to Hypoperfused Volumes

• Study Type: Interventional
• Enrollment (Actual): 106
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Hospital
    • Ann Arbor, Michigan, United States, 48105
      • Veterans Affairs (VA) Ann Arbor Healthcare System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients must have pathologically-confirmed, non-metastatic locally/regionally advanced squamous cell carcinoma of the head and neck, stage III/IV, referred for definitive chemo-RT, and meet one of the following six criteria:

  1. Primary tumor (T4) with or without metastatic lymph nodes. Tumor or nodes are: unresectable, resection is considered by the treating surgeon or patient to result in unacceptable functional or oncological results, patient refuses surgery, or surgery is not possible due to comorbidities.
  2. HPV(-) (Human Papillomavirus) or p16(-) locally/regionally advanced (T3-4 or N2-3) oropharyngeal cancer.
  3. HPV(+) or p16(+) locally/regionally advanced (T4 or N3) oropharyngeal cancer.
  4. T3 or T4 laryngeal or hypopharyngeal cancer that is locally advanced, bulky (>40 cc*), unresectable, or patient declines surgery.
  5. Stage III/IV oral cavity or paranasal sinus cancers in patients who refuse surgery or are unfit for surgery.
  6. Locally/regionally advanced (stage T3-4 and/or N3) nasopharyngeal cancer which is EBV (-) (Epstein-Barr Virus).
• KPS (Karnofsky Performance Status: A measure of general well being and activities of daily living; scores range from 0 to 100 where 100 represents perfect health) >70 (see Appendix A) within two weeks of enrollment.

• Pre-treatment laboratory criteria within four weeks of enrollment:

  • WBC (White Blood Cell) > 3500/ul, granulocyte > 1500/ul.
  • Platelet count > 100,000/ul.
  • Total Bilirubin < 1.5 X ULN.
  • AST (Aspartate Aminotransferase) and ALT (Alanine Aminotransferase) < 2.5 X ULN.
  • Estimated Creatinine clearance >30cc/min.
• Patients must be able to receive protocol chemotherapy in the judgment of the treating Medical Oncologist.
• Patients are adults (Age ≥18).
• All patients must be informed of the investigational nature of this study and given written informed consent in accordance with institutional and federal guidelines.

Exclusion Criteria:

• EBV (+) Nasopharyngeal Carcinoma in the protocol treated tumor.
• Prior head and neck radiation.
• Documented evidence of distant metastases.
• Patients with active infection.
• Pregnant women.
• Patients should have no contraindications to having a contrast enhanced MRI scan. These contraindications will be assessed at the time of enrollment using the guidelines set up and in clinical use by the Institutional Standard Practice.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control Arm; Standard chemotherapy (Cisplatin or Carboplatin) and IMRT (Intensity-Modulated Radiation Therapy)	Radiation: IMRT (Intensity-Modulated Radiation Therapy); Drug: Cisplatin; Cisplatin 40mg/m2 administered as an IV infusion prior to radiotherapy on day 1 of each week of chemo-irradiation; Drug: Carboplatin; Patients considered medically unfit to receive Cisplatin as determined by the prescribing physician, will receive Carboplatin via IV infusion on day 1 of each week of chemo-irradiation
Experimental: Boost Arm; Boost radiation to hypoperfused/low-diffusion volumes in addition to standard chemotherapy (Cisplatin or Carboplatin) and IMRT (Intensity-Modulated Radiation Therapy)	Radiation: IMRT (Intensity-Modulated Radiation Therapy); Drug: Cisplatin; Cisplatin 40mg/m2 administered as an IV infusion prior to radiotherapy on day 1 of each week of chemo-irradiation; Drug: Carboplatin; Patients considered medically unfit to receive Cisplatin as determined by the prescribing physician, will receive Carboplatin via IV infusion on day 1 of each week of chemo-irradiation; Radiation: Boost Radiation to Hypoperfused Volumes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Free Survival (DSF) Time- 2 Year Estimate	Kaplan-Meier curves with point-wise 90% confidence intervals will be generated for each treatment arm, overall and by strata. Estimates with confidence intervals will be generated from these curves for the usual summary statistics, including median DFS times.	2 years post start of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Local-regional Control Rate	Compare local-regional control rates between the two arms at 1, 2 and 3 years. Local-regional control is defined as the absence of local-regional progression. Locoregional failure (LRF) time was defined as the time from date of diagnosis to local or regional progression. Patients without LRF at last follow-up were censored at date of last follow-up.	2 years post-treatment
Proportion of Patients in Which Hypoperfused/Low-diffusion Subvolumes Overlap With Recurrence Volumes		3 years post treatment
Percent of Patients With Adverse Events	Acute and late toxicities will be summarized descriptively by grade and type for each treatment group. The Percent of patients experiencing certain toxicity types will be calculated with score based confidence intervals. Chi-square tests will be used to test whether the proportion of patients with toxicity differs between treatment groups. ACUTE TOXICITIES ≤3MONTHS AFTER RT. LATE TOXICITIES >3MONTHS AFTER RT	3 years post treatment
Correlation Coefficient Between Continuous Dose and Perfusion Summary Measures	Pearson or Spearman rank based correlation between the continuous dose and perfusion summary measures	2 weeks post Radiation Therapy (RT)

Collaborators and Investigators

• Sponsor: University of Michigan Rogel Cancer Center
• Collaborators: National Cancer Institute (NCI); National Institutes of Health (NIH)
• Investigators: Principal Investigator: Michelle Mierzwa, M.D., University of Michigan Rogel Cancer Center

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Actual): February 22, 2023
• Study Completion (Actual): February 22, 2023

Study Registration Dates

• First Submitted: December 12, 2013
• First Submitted That Met QC Criteria: January 7, 2014
• First Posted (Estimated): January 9, 2014

Study Record Updates

• Last Update Posted (Actual): March 2, 2026
• Last Update Submitted That Met QC Criteria: February 10, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Organic Chemicals; Therapeutics; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Coordination Complexes; Platinum Compounds; Radiotherapy; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Carboplatin; Cisplatin; Radiotherapy, Intensity-Modulated
• Other Study ID Numbers: UMCC 2013.062; HUM00074305 (Other Identifier: University of Michigan); R01CA184153 (U.S. NIH Grant/Contract)