Head and Neck Neoplasms, Squamous Cell Carcinoma of Head and Neck
Conditions
Keywords
Palliative Radiotherapy, Radiation Dose Hypofractionation, Quad Shot, Split Course, Quality of Life, Cancer Pain
Brief summary
Head and neck cancer in its advanced, incurable stage causes severe symptoms such as pain, trouble swallowing, and bleeding. Palliative radiation therapy is frequently used to relieve these symptoms and improve the patient's quality of life. Currently, a standard treatment approach is the "Split Course" regimen, which takes several weeks and can cause side effects that are difficult for patients to tolerate. This study aims to evaluate a shorter, alternative radiation treatment called "Quad Shot." The hypothesis of this study is that the Quad Shot regimen will be as effective as the Split Course regimen in shrinking the tumor and controlling local symptoms, but will offer a better quality of life by reducing the overall treatment time and the severity of side effects. To test this, researchers will assign participants by chance to receive either the Quad Shot or the Split Course regimen. The research team will closely monitor tumor response, treatment side effects, and patients' quality of life for up to six months.
Detailed description
The optimal palliative radiotherapy regimen for incurable head and neck squamous cell carcinoma remains undefined. The standard approach at the Instituto Nacional de Cancerologia is the split-course regimen. Although effective for local symptom control, it requires a prolonged treatment course and is associated with significant acute toxicities that can compromise the comfort and quality of life of frail patients with a limited life expectancy. The Quad Shot regimen, a hypofractionated approach initially evaluated in the RTOG 8502 trial for pelvic malignancies, offers a substantially shorter treatment duration. It has shown promising symptom control and lower toxicity profiles in retrospective and early phase studies for head and neck cancers. However, there is a lack of prospective, randomized data directly comparing the Quad Shot regimen to the split-course approach. This is a single-center, open-label, exploratory phase II randomized controlled trial designed to compare the efficacy, safety, and tolerability of the Quad Shot regimen versus the split-course regimen. A total of 40 adult patients will be centrally randomized in a 1:1 ratio using permuted blocks of 4, stratified by tumor volume, to receive either the experimental hypofractionated regimen or the active comparator. To ensure data quality, the study will utilize an institutional REDCap database for electronic case report forms (eCRF) with double data entry and monthly quality control checks. Quality assurance of the radiotherapy plans will be enforced through peer review and patient-specific pre-treatment dosimetry. A formal interim analysis for safety and futility is planned once 50% of the recruitment target is reached. Final statistical analyses will follow the Intention-To-Treat (ITT) principle. Given the palliative nature of the cohort, competitive mortality will be factored into longitudinal statistical models (such as mixed-effects models) to adequately manage missing data without distorting efficacy and quality of life estimations.
Interventions
RADIATIONQuad Shot Radiotherapy
A hypofractionated palliative radiotherapy regimen delivering a dose of 14.8 Gy divided into 4 fractions. Each fraction is 3.7 Gy, administered twice a day (with an interval of at least 6 hours between fractions) for 2 consecutive days. This cycle can be repeated up to three times with a resting interval of 3 to 4 weeks between each cycle, provided there is no limiting toxicity or disease progression.
RADIATIONSplit Course Radiotherapy
A fractionated palliative radiotherapy regimen administered in two phases. The total dose is 60 Gy divided into 20 daily fractions of 3 Gy each. A planned resting interval of 3 to 4 weeks is introduced between the two treatment phases to maximize symptom control while maintaining acceptable toxicity.
Sponsors
Instituto Nacional de Cancerologia, Columbia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Intervention model description
Participants will be assigned in a 1:1 ratio using centralized randomization with permuted blocks of 4, stratified by tumor volume, to receive either the Quad Shot or the Split Course radiotherapy regimen.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients (\>= 18 years) with a histopathological diagnosis of incurable squamous cell carcinoma of the head and neck, not candidates for curative-intent treatment. * Metastatic or locally advanced unresectable disease, in a strictly palliative setting. * Medical indication for palliative radiotherapy. * Performance status: Karnofsky \>= 50 or ECOG \<= 3. * Clinical capacity to receive radiotherapy in an outpatient setting. * Estimated life expectancy greater than 3 months. * Presence of at least one measurable lesion according to RECIST 1.1 criteria. * Logistical capacity and willingness to adhere to follow-up clinical and radiological controls up to 6 months post-treatment. * Signed informed consent.
Exclusion criteria
* History of previous radiotherapy to the same anatomical region to be treated. * Diagnosis of a second active malignancy that could interfere with the evaluation of oncological outcomes. * Presence of clinical instability or severe comorbidities that contraindicate radiotherapy treatment. * Severe cognitive or psychiatric alterations that prevent the understanding of the nature of the study, signing the consent form, or adherence to the protocol. * Women who are pregnant or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Local Tumor Response Rate Assessed by RECIST 1.1 | Exactly 3 months (12 weeks) from the date of randomization | The proportion of patients achieving an objective local tumor response, defined as either a Complete Response (CR) or a Partial Response (PR), evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. |
| Change in Quality of Life Assessed by FACT-H&N | Baseline, at the end of radiotherapy treatment, 3 months, and 6 months from the date of randomization | Mean change from baseline in patient-reported quality of life, measured by the Functional Assessment of Cancer Therapy-Head and Neck (FACT-H\&N) questionnaire. The FACT-H\&N assesses physical, social/family, emotional, and functional well-being, along with head and neck specific concerns. Higher scores indicate a better quality of life. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Acute Treatment-Related Toxicity | From the start of treatment up to 3 months from the date of randomization | The proportion of patients experiencing acute adverse events (Grade 2 or higher) associated with the radiotherapy regimens. Toxicities will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. |
Contacts
CONTACTOscar Gamboa, Medical Doctor
CONTACTSantiago Ardila Giraldo, Medical Doctor
PRINCIPAL_INVESTIGATOROscar Gamboa, Md
Instituto Nacional de Cancerologia, Columbia
Outcome results
None listed