Surgery With or Without Adjuvant Stereotactic Body Radiotherapy

A Prospective, Randomized Phase II Study of Surgery With or Without Adjuvant Stereotactic Body Radiotherapy (SBRT) in Patients With Previously-Irradiated Head and Neck Cancer

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02516969

Enrollment

Registered

2015-08-06

Start date

2015-08-31

Completion date

2021-08-06

Last updated

2022-01-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Head and Neck Cancer

Keywords

Stereotactic Body Radiotherapy (SBRT)

Brief summary

Comparison of patients with operable, recurrent previously-irradiated squamous cell head-and-neck cancers with or without adjuvant SBRT.

Detailed description

This study aims to determine prognostic factors that may predict the likelihood of local failure, regional failure, to guide future management, to compare the impact of adjuvant SBRT versus a wait-and-see approach on patient reported quality of life (PR-QoL), and to compare surgical versus SBRT-induced immunological serum markers in relation to local control. Recruitment includes patients with recurrent or second-primary head-and-neck squamous cell carcinomas within a previously-irradiated field with high-risk features compromised/positive surgical margins or extra-nodal extension) following macroscopic complete (R0/R1) salvage surgery. Participants receive Stereotactic Body Radiotherapy at the following levels: Treatment Volumes \<25cc will receive 40Gy (5 fractions of 8Gy per fraction) or treatment Volumes ≥25cc will receive 44-50Gy (5 fractions of 8.8-10Gy per fraction). Ideally all tumors volumes ≥25cc will receive 50Gy over 5 fractions, however at the discretion of the treating radiation oncologist based on tumor bed volume, prior radiation dose, and proximity to critical organs the dose can be reduced to 44Gy over 5 fractions as outlined in prior SBRT protocols. Evaluations to compare the efficacy of adjuvant SBRT versus wait-and-see, include Local Control, Regional and distant control, Progression-free survival, Overall survival and Patient-Reported Quality-of-Life (PR-QoL). Evaluations conducted to assess the safety of adjuvant SBRT following salvage surgery include recording of all toxicity data per National Cancer Institute Common Toxicity Criteria Events Scale version 4.0 and prospectively administering the previously-validated University of Washington Quality-of-Life-Revised (UW-QoL-R) questionnaire measuring patient-reported quality-of-life (PR-QoL).

Interventions

RADIATIONStereotactic Body Radiotherapy

Radiation

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Pathologically proven recurrent or second-primary head-and-neck cancer receiving prior radiotherapy with or without chemotherapy. * Prior radiotherapy to a dose of ≥50Gy * No evidence of distant metastases * Macroscopic complete salvage surgery with curative intent (surgery was not performed only for biopsy or palliation). Final pathology and imaging must indicate a R0 or R1 resection (no gross disease remaining). * High-risk pathologic features must be present: compromised/positive surgical margins (≤ 2mm) or extra-nodal extension (patient with other high-risk features gross perinueral invasion, bone invasion, angiolyphatic invasion, or a constellation of these factors may be eligible based on case-by-case basis at discretion of principal investigator). * Karnofsky Performance Status ≥60 (ECOG 0-2) * Any number or type of prior chemotherapy is allowed (patient may receive concurrent or adjuvant systemic therapy such as cetuximab at the discretion of the treating oncologic team)

Exclusion criteria

* Evidence of distant metastases on any staging or imaging modality * Women who are breast feeding, or have a positive pregnancy test (reproductive age should use effective birth control during study if randomized to SBRT treatment arm) * Any patient with gross residual disease following salvage surgery * Any co-morbidity or condition of sufficient severity to limit full compliance with the protocol per assessment by the principal investigator.

Design outcomes

Primary

Measure	Time frame	Description
1-year Local Control	Up to 1 year	Local progression-free-survival (LPFS) is the number of months from the initiation of study treatment until (local) progression of disease or death from any cause. Progression is defined as the appearance of a new metastatic lesion or objective tumor progression. Clinically detected lesions will only be considered measurable when superficial (vis-à-vis skin modules and palpable lymph nodes). The lesion must be accurately measured in at least one dimension ≥ 10mm. Methods for measuring disease status include CT, PET/CT or MRI.

Secondary

Measure	Time frame	Description
Number of Participants With Late Toxicities of Adjuvant SBRT	Up to 2 years	Toxicities will be assessed according to the National Cancer Institute Common Toxicity Criteria Events Scale (CTCAE), v4. Late toxicities will be those seen after 3 months of completion of Stereotactic Body Radiotherapy. Adverse events are Grade 1 and 2 and Serious Adverse events are Grade 3 and 4 events.
Progression-free Survival (PFS) Locoregional	Up to 2 years	LRPFS is defined as the time from the date of randomization to the date of local or regional recurrence, whichever occurs first, or the date of death from any cause. Subjects who are alive and have not progressed will be censored at their last follow-up date. Progression is defined as the appearance of a new metastatic lesion or objective tumor progression. Clinically detected lesions will only be considered measurable when superficial (vis-à-vis skin modules and palpable lymph nodes). The lesion must be accurately measured in at least one dimension ≥ 10mm. Methods for measuring disease status include CT, PET/CT or MRI.
Progression-free Survival (DPFS) Distant	Up to 2 years	Distant progression-free-survival (DPFS) is the time from the date of randomization to the date of distant progression or the date of death from any cause. Progression is defined as the appearance of a new metastatic lesion or objective tumor progression. Clinically detected lesions will only be considered measurable when superficial (vis-à-vis skin modules and palpable lymph nodes). The lesion must be accurately measured in at least one dimension ≥ 10mm. Methods for measuring disease status include CT, PET/CT or MRI.
Number of Participants With Acute Toxicities of Adjuvant SBRT	Up to 2 years	Toxicities are assess according to the National Cancer Institute Common Toxicity Criteria Events Scale (CTCAE), v4. Acute toxicities are those seen within 3 months of completion of Stereotactic Body Radiotherapy. Toxicity in patients is documented immediately prior to randomization and 8-12 weeks post-treatment. Adverse events are Grade 1 and 2 and Serious Adverse events are Grade 3 and 4 events.
Overall Survival (OS)	Up to 5 years	The overall survival time is the measurement of time between the date of randomization and death from any cause.
Quality of Life (UW-QoL-R)	Up to 2 years	The University of Washington Quality of Life questionnaire (revised) is a self-administered 16 item inquiry given to patients with head and neck cancer. The first 12 items ask the patient to score domains (such as pain, appearance, swallowing) from 0 (worse) to 100 (best). The arithmetic mean is then computed, yielding one number between 0 and 100. The higher the number, the better the patient is considered to be faring. The item simply asks the patient to choose the top 3 issues which have been bothering the patient over the past 7 days. The issues include physical symptoms, emotions and appearance. The final 3 questions provide a global assessment by asking the patient to consider their overall well-being over the past 7 days and provide possible answers ranging from excellent to very poor. For trial analysis: Period=1: before surgery, Period=2: after surgery, but before SBRT for patients in the SBRT arm, Period=3: after SBRT.
Overall Progression Free Survival (PFS)	Up to 2 years	Overall progression free survival is the total of the three survival time measurements; PFS = local + regional + distant. Progression is defined as the appearance of a new metastatic lesion or objective tumor progression. Clinically detected lesions will only be considered measurable when superficial (vis-à-vis skin modules and palpable lymph nodes). The lesion must be accurately measured in at least one dimension ≥ 10mm. Methods for measuring disease status include CT, PET/CT or MRI.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Stereotactic Body Radiotherapy Stereotactic Body Radiotherapy at the following levels: Treatment Volumes \<25cc will receive 40Gy (5 fractions of 8Gy per fraction) or treatment Volumes ≥25cc will receive 44-50Gy (5 fractions of 8.8-10Gy per fraction). Ideally all tumors volumes ≥25cc will receive 50Gy over 5 fractions, however at the discretion of the treating radiation oncologist based on tumor bed volume, prior radiation dose, and proximity to critical organs the dose can be reduced to 44Gy over 5 fractions as outlined in prior SBRT protocols.	3
Observation Cohort No Stereotactic Body Radiotherapy	4
Total	7

Baseline characteristics

Characteristic	Stereotactic Body Radiotherapy	Observation Cohort	Total
Age, Continuous	63 years	64 years	63 years
Karnofsky Performance Status (KPS)	80.0 score on a scale	80.0 score on a scale	80.0 score on a scale
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 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	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	3 Participants	4 Participants	7 Participants
Sex: Female, Male Female	2 Participants	0 Participants	2 Participants
Sex: Female, Male Male	1 Participants	4 Participants	5 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 3	2 / 4
other Total, other adverse events	3 / 3	2 / 4
serious Total, serious adverse events	2 / 3	0 / 4

Outcome results

Primary

1-year Local Control

Local progression-free-survival (LPFS) is the number of months from the initiation of study treatment until (local) progression of disease or death from any cause. Progression is defined as the appearance of a new metastatic lesion or objective tumor progression. Clinically detected lesions will only be considered measurable when superficial (vis-à-vis skin modules and palpable lymph nodes). The lesion must be accurately measured in at least one dimension ≥ 10mm. Methods for measuring disease status include CT, PET/CT or MRI.

Time frame: Up to 1 year