Oropharyngeal Cancer
Conditions
Brief summary
The purpose of this study is to find out whether radiotherapy to some of the lymph node areas can be safely omitted to decrease side effects without increasing the risk of the tumour coming back.
Detailed description
The standard or usual treatment for this disease includes radiotherapy or radiotherapy combined with chemotherapy or antibody therapy. These treatments are highly effective at curing most patients with HPV-related cancer of the oropharynx, but short and long-term side effects from treatment can be significant.
Interventions
RADIATIONRadiation
35 fractions, 5/wk, 7 wks 70Gy/56Gy, or 35 fractions, 6/wk, 6 wks, 70Gy/56Gy, or 35 fractions, 5/wk, 7 wks OR 6/wk, 6 wks 70Gy/56Gy
DRUGCisplatin
100 mg/m2 on day 1, 22, and 43 or 40 mg/m2 /wk for 7 wks
Sponsors
Canadian Cancer Trials Group
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with pathologically proven diagnosis of HPV-related OPSCC * Clinical stage T1-3 N0-1 M0 (UICC/AJCC 8th Ed.) * Patients must be eligible for definitive RT or CRT * Must be ≥ 18 years of age * Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 * Patient is able (i.e. sufficiently fluent) and willing to complete the quality of life and health economics questionnaires in either English or French * Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrolment in the trial to document their willingness to participate * Patients must be accessible for treatment and follow-up. Investigators must assure themselves the patients enrolled on this trial will be available for complete documentation of the treatment, adverse events, and follow-up. * In accordance with CCTG policy, protocol treatment is to begin within 3 weeks of patient registration * Women/men of childbearing potential must have agreed to use a highly effective contraceptive method * The following radiological investigations must be done within 8 weeks of randomization: CT or MR of head and neck (MRI is recommended for base-of-tongue primary tumors); PET-CT scan. * Patient must consent to provision of, and investigator(s) must confirm location and commit to obtain a representation of formalin-fixed paraffin block of non-cytology tumour tissue in order that the specific correlative marker assays described in Section 12 (Correlative Studies) may be conducted. Please see the Correlative Manual for details * Patient must consent to provision of samples of blood and plasma (for circulating cell free DNA) in order that the specific correlative marker assays described may be conducted. * Patients with prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
Exclusion criteria
* Previous chemotherapy or radiotherapy treatment for head and neck cancer * Patients with an unknown primary.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Event-free Survival | 2 years | Event free survival (EFS) is defined as the time from the date of registration to the date of first record of any of the following events: * Progression. * Surgery. * Non-protocol RT, chemotherapy, or biologic therapy (for the current cancer diagnosis) without documentation of the site of failure. * Death due to any cause. The outcome is reported as the proportion of patients who remain event-free at 2 years. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 2 years | For patients who have died, overall survival is calculated in months from the day of registration to date of death. Otherwise, overall survival is censored at the last day the patient is known alive (LKA). The outcome is reported as the proportion of patients who remain alive at 2 years. |
| Local-regional Control | 2 years | Local-regional control is defined as the time from the date of registration to the date of any of the following, whichever comes first: * Surgery of primary tumour at any time performed for clinical or radiological disease persistence/progression/recurrence with tumour present/unknown on final pathology. * Neck dissection \> 20 weeks from the end of radiation therapy performed for clinical or radiological (RECIST 1.1) disease persistence/progression/recurrence within target volumes with tumour present/unknown on final pathology. * Neck dissection at any time after registration performed for clinical or radiological disease recurrence/progression outside the target volumes or without documentation of the site of failure with tumour present/unknown on final pathology. * the first record of appearance (radiological or clinical) of local or regional disease progression. The outcome is reported as the proportion of patients who remain local-regional control free at 2 years. |
| Out-of-field Regional Control | 2 years | Time to out-of-field regional failure is defined as the time from the date of registration to the date of the first record of appearance of regional progression/recurrence outside the treatment field , or to the date of neck dissection at any time after registration with tumour present/unknown performed for clinical or radiological disease progression outside the target volumes whichever comes first. The outcome is reported as the proportion of patients who remain out-of-field regional control free at 2 years. |
| Distant Metastasis Free Survival | 2 years | Distant metastasis free survival is defined as the time from the date of registration to the date of first record of appearance of distant metastasis or death for any cause. Local-regional failure or second cancers diagnosed before the distant metastases are not considered events of interest for this endpoint. Subjects alive and free of distant metastasis are censored at the date of the most recent follow-up examination. The outcome is reported as the proportion of patients who remain distant metastasis event-free at 2 years. |
Countries
Canada
Contacts
STUDY_CHAIRScott Bratman
Princess Margaret Cancer Centre, Toronto, ON
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Experimental Arm Elective volume adjusted de-escalation radiotherapy.
Option #1 - Radiotherapy 35 fractions, 5/wk, 7 wks 70Gy/56Gy Cisplatin 100mg/m2 on day 1, 22 and 43 or 40mg mg/m2/wk for 7 wks
Option #2 - Radiation only-35 fraction, 6/wk, 6wks 70Gy/56Gy | 103 |
| Total | 103 |
Baseline characteristics
| Characteristic | Experimental Arm |
|---|---|
| Age, Continuous | 62.8 years |
| ECOG Performance Status 0 | 82 Participants |
| ECOG Performance Status 1 | 21 Participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 85 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 6 / 100 |
| other Total, other adverse events | 100 / 100 |
| serious Total, serious adverse events | 8 / 100 |
Outcome results
Primary
Event-free Survival
Event free survival (EFS) is defined as the time from the date of registration to the date of first record of any of the following events: * Progression. * Surgery. * Non-protocol RT, chemotherapy, or biologic therapy (for the current cancer diagnosis) without documentation of the site of failure. * Death due to any cause. The outcome is reported as the proportion of patients who remain event-free at 2 years.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Experimental Arm | Event-free Survival | 91.8 Percentage of patients event-free at 2y |
Secondary
Distant Metastasis Free Survival
Distant metastasis free survival is defined as the time from the date of registration to the date of first record of appearance of distant metastasis or death for any cause. Local-regional failure or second cancers diagnosed before the distant metastases are not considered events of interest for this endpoint. Subjects alive and free of distant metastasis are censored at the date of the most recent follow-up examination. The outcome is reported as the proportion of patients who remain distant metastasis event-free at 2 years.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Experimental Arm | Distant Metastasis Free Survival | 91.3 Percentages of patients DMF at 2y |
Secondary
Local-regional Control
Local-regional control is defined as the time from the date of registration to the date of any of the following, whichever comes first: * Surgery of primary tumour at any time performed for clinical or radiological disease persistence/progression/recurrence with tumour present/unknown on final pathology. * Neck dissection \> 20 weeks from the end of radiation therapy performed for clinical or radiological (RECIST 1.1) disease persistence/progression/recurrence within target volumes with tumour present/unknown on final pathology. * Neck dissection at any time after registration performed for clinical or radiological disease recurrence/progression outside the target volumes or without documentation of the site of failure with tumour present/unknown on final pathology. * the first record of appearance (radiological or clinical) of local or regional disease progression. The outcome is reported as the proportion of patients who remain local-regional control free at 2 years.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Experimental Arm | Local-regional Control | 94.8 Percentage of patients LRC free at 2y |
Secondary
Out-of-field Regional Control
Time to out-of-field regional failure is defined as the time from the date of registration to the date of the first record of appearance of regional progression/recurrence outside the treatment field , or to the date of neck dissection at any time after registration with tumour present/unknown performed for clinical or radiological disease progression outside the target volumes whichever comes first. The outcome is reported as the proportion of patients who remain out-of-field regional control free at 2 years.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Experimental Arm | Out-of-field Regional Control | 99 Percentages of patients ORC free at 2y |
Secondary
Overall Survival
For patients who have died, overall survival is calculated in months from the day of registration to date of death. Otherwise, overall survival is censored at the last day the patient is known alive (LKA). The outcome is reported as the proportion of patients who remain alive at 2 years.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Experimental Arm | Overall Survival | 94.7 Percentage of patients alive at 2 years |