Surgery With or Without Adjuvant Stereotactic Body Radiotherapy

• ClinicalTrials.gov Identifier: NCT02516969
• Recruitment Status: Completed
• First Posted: August 6, 2015
• Results First Posted: January 14, 2022
• Last Update Posted: January 14, 2022
• Sponsor: David A. Clump, MD, PhD
• Information provided by (Responsible Party): David A. Clump, MD, PhD, University of Pittsburgh

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Head and Neck Cancer	Radiation: Stereotactic Body Radiotherapy	Not Applicable

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).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 7 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: August 2015
• Actual Primary Completion Date: May 30, 2019
• Actual Study Completion Date: August 6, 2021

Arms and Interventions

Arm

Intervention/treatment

Experimental: Stereotactic Body Radiotherapy; Subjects will 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.

Radiation: Stereotactic Body Radiotherapy; Radiation; Other Name: SBRT

Outcome Measures

Primary Outcome Measures :

1. 1-year Local Control [ Time Frame: 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 Outcome Measures :

1. Number of Participants With Acute Toxicities of Adjuvant SBRT [ Time Frame: 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.
2. Number of Participants With Late Toxicities of Adjuvant SBRT [ Time Frame: 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.
3. Progression-free Survival (PFS) Locoregional [ Time Frame: 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.
4. Progression-free Survival (DPFS) Distant [ Time Frame: 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.
5. Overall Progression Free Survival (PFS) [ Time Frame: 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.
6. Overall Survival (OS) [ Time Frame: Up to 5 years ]
   The overall survival time is the measurement of time between the date of randomization and death from any cause.
7. Quality of Life (UW-QoL-R) [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Pennsylvania

UPMC Shadyside Radiation Oncology

Pittsburgh, Pennsylvania, United States, 15232

Sponsors and Collaborators

David A. Clump, MD, PhD

Investigators

• Principal Investigator: David A Clump, MD; University of Pittsburgh

  Study Documents (Full-Text)

Documents provided by David A. Clump, MD, PhD, University of Pittsburgh:

Study Protocol and Statistical Analysis Plan  [PDF] April 29, 2020

More Information

• Responsible Party: David A. Clump, MD, PhD, Associate Professor, University of Pittsburgh
• ClinicalTrials.gov Identifier: NCT02516969
• Other Study ID Numbers: 14-151
• First Posted: August 6, 2015
• Results First Posted: January 14, 2022
• Last Update Posted: January 14, 2022
• Last Verified: December 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes

Keywords provided by David A. Clump, MD, PhD, University of Pittsburgh:

Stereotactic Body Radiotherapy (SBRT)

Additional relevant MeSH terms:

Head and Neck Neoplasms; Neoplasms by Site; Neoplasms