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

Phase 2
Active, not recruiting
Conditions
Squamous Cell Carcinoma of the Head and Neck
Interventions
Radiation: IMRT (Intensity-Modulated Radiation Therapy)
Radiation: Boost Radiation to Hypoperfused Volumes
Registration Number
NCT02031250
Lead Sponsor
University of Michigan Rogel Cancer Center
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
106
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Boost ArmBoost Radiation to Hypoperfused VolumesBoost radiation to hypoperfused/low-diffusion volumes in addition to standard chemotherapy (Cisplatin or Carboplatin) and IMRT (Intensity-Modulated Radiation Therapy)
Control ArmCisplatinStandard chemotherapy (Cisplatin or Carboplatin) and IMRT (Intensity-Modulated Radiation Therapy)
Boost ArmIMRT (Intensity-Modulated Radiation Therapy)Boost radiation to hypoperfused/low-diffusion volumes in addition to standard chemotherapy (Cisplatin or Carboplatin) and IMRT (Intensity-Modulated Radiation Therapy)
Control ArmIMRT (Intensity-Modulated Radiation Therapy)Standard chemotherapy (Cisplatin or Carboplatin) and IMRT (Intensity-Modulated Radiation Therapy)
Boost ArmCarboplatinBoost radiation to hypoperfused/low-diffusion volumes in addition to standard chemotherapy (Cisplatin or Carboplatin) and IMRT (Intensity-Modulated Radiation Therapy)
Control ArmCarboplatinStandard chemotherapy (Cisplatin or Carboplatin) and IMRT (Intensity-Modulated Radiation Therapy)
Boost ArmCisplatinBoost radiation to hypoperfused/low-diffusion volumes in addition to standard chemotherapy (Cisplatin or Carboplatin) and IMRT (Intensity-Modulated Radiation Therapy)
Primary Outcome Measures
NameTimeMethod
Disease Free Survival (DSF) time3 years post treatment

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 and DFS at 1, 2, and 3 years.

Secondary Outcome Measures
NameTimeMethod
Number of patients with adverse events3 years post treatment

Acute and late toxicities will be summarized descriptively by grade and type for each treatment group. The proportion 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.

Proportion of patients in which hypoperfused/low-diffusion subvolumes overlap with recurrence volumes3 years post treatment
Local-regional control rate3 years post-treatment

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.

Correlation coefficient between continuous dose and perfusion summary measures2 weeks post Radiation Therapy (RT)

Pearson or Spearman rank based correlation between the continuous dose and perfusion summary measures

Trial Locations

Locations (2)

University of Michigan Hospital

🇺🇸

Ann Arbor, Michigan, United States

Veterans Affairs (VA) Ann Arbor Healthcare System

🇺🇸

Ann Arbor, Michigan, United States

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