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

NCT02031250 | Completed Phase 2 Results DMC

• 3 other identifiers: UMCC 2013.062HUM00074305R01CA184153
• Study Type: interventional
• Target: 106
• Locations: 1 country
• Sites: 2

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.

Conditions

Squamous Cell Carcinoma of the Head and Neck

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Local-regional Control Rate

  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

  3 years post treatment

• Correlation Coefficient Between Continuous Dose and Perfusion Summary Measures

  2 weeks post Radiation Therapy (RT)

Study Arms (2)

Control Arm

ACTIVE COMPARATOR

Standard chemotherapy (Cisplatin or Carboplatin) and IMRT (Intensity-Modulated Radiation Therapy)

Drug: Cisplatin; Drug: Carboplatin; Radiation: IMRT (Intensity-Modulated Radiation Therapy)

Boost Arm

EXPERIMENTAL

Boost radiation to hypoperfused/low-diffusion volumes in addition to standard chemotherapy (Cisplatin or Carboplatin) and IMRT (Intensity-Modulated Radiation Therapy)

Drug: Cisplatin; Drug: Carboplatin; Radiation: IMRT (Intensity-Modulated Radiation Therapy); Radiation: Boost Radiation to Hypoperfused Volumes

Interventions

Cisplatin DRUG

Cisplatin 40mg/m2 administered as an IV infusion prior to radiotherapy on day 1 of each week of chemo-irradiation

Boost Arm; Control Arm

Carboplatin DRUG

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

Boost Arm; Control Arm

IMRT (Intensity-Modulated Radiation Therapy) RADIATION

Boost Arm; Control Arm

Boost Radiation to Hypoperfused Volumes RADIATION

Boost Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead
• National Institutes of Health (NIH): collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Veterans Affairs (VA) Ann Arbor Healthcare System

Ann Arbor, Michigan, 48105, United States

Location

University of Michigan Hospital

Ann Arbor, Michigan, 48109, United States

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Cisplatin; Carboplatin; Radiotherapy, Intensity-Modulated

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics

Results Point of Contact

• Title: University of Michigan Rogel Cancer Center ClinicalTrials.gov Admin
• Organization: University of Michigan Rogel Cancer Center

ClinicalTrialsgov_CCAdmin@umich.edu

734-936-9499

Study Officials

• Michelle Mierzwa, M.D.

  University of Michigan Rogel Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2013
• First Posted: January 9, 2014
• Study Start: February 1, 2014
• Primary Completion: February 22, 2023
• Study Completion: February 22, 2023
• Last Updated: March 2, 2026
• Results First Posted: March 2, 2026

Record last verified: 2026-02

Locations

US (2)