Squamous Cell Carcinoma of the Head and Neck
Conditions
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.
Interventions
DRUGCisplatin
Cisplatin 40mg/m2 administered as an IV infusion prior to radiotherapy on day 1 of each week of chemo-irradiation
DRUGCarboplatin
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
RADIATIONBoost Radiation to Hypoperfused Volumes
Sponsors
University of Michigan Rogel Cancer Center
National Institutes of Health (NIH)
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease Free Survival (DSF) Time- 2 Year Estimate | 2 years post start of 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Local-regional Control Rate | 2 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. 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. |
| 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 | 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 |
| Correlation Coefficient Between Continuous Dose and Perfusion Summary Measures | 2 weeks post Radiation Therapy (RT) | Pearson or Spearman rank based correlation between the continuous dose and perfusion summary measures |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORMichelle Mierzwa, M.D.
University of Michigan Rogel Cancer Center
Participant flow
Pre-assignment details
132 patients were screened resulting in 26 screen failures. 6 patients were enrolled but withdrew from the study before being randomized
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 15 Participants |
| Age, Categorical Between 18 and 65 years | 60 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 49 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants |
| Race (NIH/OMB) White | 79 Participants |
| Region of Enrollment United States | 100 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 14 / 59 | 15 / 41 |
| other Total, other adverse events | 59 / 59 | 38 / 41 |
| serious Total, serious adverse events | 15 / 59 | 12 / 41 |
Outcome results
None listed