search
Back to results

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

Primary Purpose

Squamous Cell Carcinoma of the Head and Neck

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Cisplatin
Carboplatin
IMRT (Intensity-Modulated Radiation Therapy)
Boost Radiation to Hypoperfused Volumes
Sponsored by
University of Michigan Rogel Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Squamous Cell Carcinoma of the Head and Neck

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Veterans Affairs (VA) Ann Arbor Healthcare System
  • University of Michigan Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Control Arm

Boost Arm

Arm Description

Standard chemotherapy (Cisplatin or Carboplatin) and IMRT (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)

Outcomes

Primary Outcome Measures

Disease Free Survival (DSF) time
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

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.
Proportion of patients in which hypoperfused/low-diffusion subvolumes overlap with recurrence volumes
Number of patients with adverse events
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.
Correlation coefficient between continuous dose and perfusion summary measures
Pearson or Spearman rank based correlation between the continuous dose and perfusion summary measures

Full Information

First Posted
December 12, 2013
Last Updated
August 30, 2023
Sponsor
University of Michigan Rogel Cancer Center
Collaborators
National Institutes of Health (NIH)
search

1. Study Identification

Unique Protocol Identification Number
NCT02031250
Brief Title
Randomized Phase II Study of DCE-MRI-based Dose Escalation for Poor-prognosis and Neck Cancer
Official Title
Randomized Phase II Study of DCE-MRI-based Dose Escalation for Poor-prognosis and Neck Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
February 2014 (undefined)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Michigan Rogel Cancer Center
Collaborators
National Institutes of Health (NIH)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Squamous Cell Carcinoma of the Head and Neck

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
106 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Control Arm
Arm Type
Active Comparator
Arm Description
Standard chemotherapy (Cisplatin or Carboplatin) and IMRT (Intensity-Modulated Radiation Therapy)
Arm Title
Boost Arm
Arm Type
Experimental
Arm Description
Boost radiation to hypoperfused/low-diffusion volumes in addition to standard chemotherapy (Cisplatin or Carboplatin) and IMRT (Intensity-Modulated Radiation Therapy)
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Intervention Description
Cisplatin 40mg/m2 administered as an IV infusion prior to radiotherapy on day 1 of each week of chemo-irradiation
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Intervention Description
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
Intervention Type
Radiation
Intervention Name(s)
IMRT (Intensity-Modulated Radiation Therapy)
Intervention Type
Radiation
Intervention Name(s)
Boost Radiation to Hypoperfused Volumes
Primary Outcome Measure Information:
Title
Disease Free Survival (DSF) time
Description
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.
Time Frame
3 years post treatment
Secondary Outcome Measure Information:
Title
Local-regional control rate
Description
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.
Time Frame
3 years post-treatment
Title
Proportion of patients in which hypoperfused/low-diffusion subvolumes overlap with recurrence volumes
Time Frame
3 years post treatment
Title
Number of patients with adverse events
Description
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.
Time Frame
3 years post treatment
Title
Correlation coefficient between continuous dose and perfusion summary measures
Description
Pearson or Spearman rank based correlation between the continuous dose and perfusion summary measures
Time Frame
2 weeks post Radiation Therapy (RT)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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: 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. HPV(-) (Human Papillomavirus) or p16(-) locally/regionally advanced (T3-4 or N2-3) oropharyngeal cancer. HPV(+) or p16(+) locally/regionally advanced (T4 or N3) oropharyngeal cancer. T3 or T4 laryngeal or hypopharyngeal cancer that is locally advanced, bulky (>40 cc*), unresectable, or patient declines surgery. Stage III/IV oral cavity or paranasal sinus cancers in patients who refuse surgery or are unfit for surgery. 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michelle Mierzwa, M.D.
Organizational Affiliation
University of Michigan Rogel Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Veterans Affairs (VA) Ann Arbor Healthcare System
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48105
Country
United States
Facility Name
University of Michigan Hospital
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs