Oropharynx Cancer
Conditions
Brief summary
This study is designed for patients with a cancer of the oropharynx (tonsils or base of tongue) caused by the HPV virus. Traditional treatment involves surgery followed by six weeks of daily radiation therapy. This study investigates a less intense radiation treatment following surgery that uses half the dose of radiation given over two weeks rather than six weeks. Patients will be randomly assigned to receive the less intense treatment versus the traditional treatment by coin flip. Patients are twice as likely to receive the less intense treatment during randomization.
Detailed description
Recent studies suggest that tumors in the oropharynx (tonsils or base of tongue) caused by the HPV virus are much more sensitive to radiation and chemotherapy. Standard treatment for HPV associated oropharynx tumor after surgery involves six weeks of radiation therapy and has many long term side effects and complications. Mayo Clinic recently piloted a study investigating whether patients with HPV-associated oropharynx tumors can receive less radiation and chemotherapy after surgery when compared with the standard treatment. The investigators current study will compare the new, shorter treatment course (2 weeks of treatment) with the standard course of treatment (six weeks). Patients will be randomized to either the less intense or standard treatment arm. Patients will be twice as likely to receive the less intense treatment during randomization.
Interventions
RADIATIONAdjuvant Radiation Therapy
60 Gy / 2 Gy fractions (standard arm) 30 - 36 Gy / 1.5 - 1.8 Gy b.i.d. fractions (experimental arm)
DRUGDocetaxel
15 mg/m2. Experimental arm only.
DRUGCisplatin
40 mg/m2. Standard arm only.
Sponsors
Mayo Clinic
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
* Age ≥ 18 years. * Histological confirmation of HPV+ squamous cell carcinoma of the oropharynx. HPV positivity will be defined as positive staining for p16 on immunohistochemistry (IHC). * Gross total surgical resection with curative intent of the primary tumor and at least unilateral neck dissection within 7 weeks of registration. * ECOG Performance Status (PS) 0 or 1 * Absence of distant metastases on standard diagnostic work-up ≤ 10 weeks prior to registration. (Chest CT, Chest x-ray (CXR), or PET/CT.) * Must have one of the following risk factors: * Lymph node \> 3 cm * 2 or more positive lymph nodes * Perineural invasion * Lymphovascular space invasion * T3 or T4 primary disease * Lymph node extracapsular extension * The following laboratory values obtained ≥14 days prior to registration. * Absolute neutrophil count (ANC) ≥1500/mm3 * Platelet count ≥100,000/mm3 * Hemoglobin ≥8.0g/dL * Creatinine ≤ 1.5 mg/dL or creatinine clearance ≥ 50 mL/min * Total bilirubin \< 2 x institutional upper limit of normal (ULN) * AST or ALT \< 3 x institutional ULN * Negative pregnancy test done ≤7 days prior to registration, for women of childbearing potential only. * Ability to complete questionnaire(s) by themselves or with assistance. * Provide informed written consent. * Willingness to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study).
Exclusion criteria
* Any of the following because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects: * Pregnant women * Nursing women * Men or women of childbearing potential who are unwilling to employ adequate contraception * Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens. * Immunocompromised patients and patients known to be HIV positive. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm. * Other active malignancy ≤ 5 years prior to registration. EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix. NOTE: If there is a history or prior malignancy, they must not be receiving other specific treatment for their cancer. * Prior history of radiation therapy to the affected site. * History of connective tissue disorders such as rheumatoid arthritis, lupus, or Sjogren's disease. * Presence of any of the following risk factors after surgery: * Any positive surgical margin. * Adenopathy below the clavicles * Prior systemic chemotherapy. * Receiving any medications or substances which in the opinion of the investigators would interfere with treatment. Examples could include strong inhibitors of CYP3A4 at oncologist discretion (see Appendix IV). * Severe pre-existing ototoxicity or neuropathy that would, in the opinion of the investigator, preclude the use of cisplatin chemotherapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Grade 3+ Adverse Events Rate | 2 years | To compare rate of late grade 3-5 toxicities between de-escalated adjuvant radiation therapy (DART) and standard adjuvant therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quality of Life Between DART and Standard Adjuvant Therapy - FACT-HN | 1 year | To compare the overall QOL between DART and standard adjuvant therapy at 1-year post-treatment as measured by the Functional Assessment of Cancer Therapy - Head & Neck (FACT-HN) questionnaire. The FACT-HN consists of 12 questions related to symptoms and feeling over the past 7 days. Items are answered on a scale of 0-4 where 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, and 4=very much. |
| Quality of Life Between DART and Standard Adjuvant Therapy - EORTC-QLQ-HN35 | 1 year | To compare the overall QOL between DART and standard adjuvant therapy at 1-year post-treatment as measured by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Head and Neck Module (EORTC-QLQ-HN35). The questionnaire consists of 35 items related to symptoms or problems during the past week. Thirty (30) items are answered on a scale of 0-4 where 0=not at all; 1=a little; 3=quite a bit, and 4=very much, and five (5) items are answered with yes/no. |
| Local/Regional Control | 2 years | Local/regional failure percentage as assessed by imaging or physical exam at 2 years after study registration for patients treated with DART vs standard therapy. |
| Disease-free Survival | 2 years | Percentage of patients disease free and alive at 2 years. |
| Distant Failure Associated With DART vs Standard Treatment | 2 years | Distant failure is defined as cancer that has recurred or spread to a part of the body far away from the original tumor site |
| Overall Survival | 2 years | Percentage of patients alive at 2 years. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| De-escalated Adjuvant Radiation Therapy (DART) Docetaxel 15 mg/m2 days 1, 8 and Radiation Therapy (RT) 30 Gy/1.5 Gy fractions twice daily (b.i.d.) days 1-12 only (intermediate risk) or 36 Gy/1.8 Gy b.i.d. fractions (high risk)\> \> Adjuvant Radiation Therapy: 60 Gy / 2 Gy fractions (standard arm)\> 30 - 36 Gy / 1.5 - 1.8 Gy b.i.d. fractions (experimental arm)\>
\> Docetaxel: 15 mg/m2. Experimental arm only. | 136 |
| Standard of Care Treatment (SOC) RT 60 Gy/2 Gy fractions daily (qday) days 1-40. \> For high risk, add weekly Cisplatin 40 mg/m2 (Around days 1, 8, 15, 22, 29, 36)\> \> Adjuvant Radiation Therapy: 60 Gy / 2 Gy fractions (standard arm)\> 30 - 36 Gy / 1.5 - 1.8 Gy b.i.d. fractions (experimental arm)\>
\> Cisplatin: 40 mg/m2. Standard arm only. | 92 |
| Total | 228 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 8 | 28 |
Baseline characteristics
| Characteristic | Standard of Care Treatment (SOC) | Total | De-escalated Adjuvant Radiation Therapy (DART) |
|---|---|---|---|
| Age, Continuous | 58 years | 59 years | 59 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 4 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 84 Participants | 207 Participants | 123 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 7 Participants | 17 Participants | 10 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 9 Participants | 5 Participants |
| Race (NIH/OMB) White | 87 Participants | 215 Participants | 128 Participants |
| Sex: Female, Male Female | 11 Participants | 26 Participants | 15 Participants |
| Sex: Female, Male Male | 81 Participants | 202 Participants | 121 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 136 | 9 / 92 |
| other Total, other adverse events | 128 / 136 | 60 / 92 |
| serious Total, serious adverse events | 0 / 136 | 1 / 92 |
Outcome results
Primary
Grade 3+ Adverse Events Rate
To compare rate of late grade 3-5 toxicities between de-escalated adjuvant radiation therapy (DART) and standard adjuvant therapy.
Time frame: 2 years
Population: All treated patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| De-escalated Adjuvant Radiation Therapy (DART) | Grade 3+ Adverse Events Rate | .032 events per participant |
| Standard of Care Treatment (SOC) | Grade 3+ Adverse Events Rate | .115 events per participant |
Secondary
Disease-free Survival
Percentage of patients disease free and alive at 2 years.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| De-escalated Adjuvant Radiation Therapy (DART) | Disease-free Survival | 88.2 percentage of participants |
| Standard of Care Treatment (SOC) | Disease-free Survival | 96.6 percentage of participants |
Secondary
Distant Failure Associated With DART vs Standard Treatment
Distant failure is defined as cancer that has recurred or spread to a part of the body far away from the original tumor site
Time frame: 2 years
Secondary
Local/Regional Control
Local/regional failure percentage as assessed by imaging or physical exam at 2 years after study registration for patients treated with DART vs standard therapy.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| De-escalated Adjuvant Radiation Therapy (DART) | Local/Regional Control | 95.9 percentage of participants |
| Standard of Care Treatment (SOC) | Local/Regional Control | 98.3 percentage of participants |
Secondary
Overall Survival
Percentage of patients alive at 2 years.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| De-escalated Adjuvant Radiation Therapy (DART) | Overall Survival | 96.9 percentage of participants |
| Standard of Care Treatment (SOC) | Overall Survival | 98.3 percentage of participants |
Secondary
Quality of Life Between DART and Standard Adjuvant Therapy - EORTC-QLQ-HN35
To compare the overall QOL between DART and standard adjuvant therapy at 1-year post-treatment as measured by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Head and Neck Module (EORTC-QLQ-HN35). The questionnaire consists of 35 items related to symptoms or problems during the past week. Thirty (30) items are answered on a scale of 0-4 where 0=not at all; 1=a little; 3=quite a bit, and 4=very much, and five (5) items are answered with yes/no.
Time frame: 1 year
Secondary
Quality of Life Between DART and Standard Adjuvant Therapy - FACT-HN
To compare the overall QOL between DART and standard adjuvant therapy at 1-year post-treatment as measured by the Functional Assessment of Cancer Therapy - Head & Neck (FACT-HN) questionnaire. The FACT-HN consists of 12 questions related to symptoms and feeling over the past 7 days. Items are answered on a scale of 0-4 where 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, and 4=very much.
Time frame: 1 year