Stereotactic Ablative Radiotherapy for Oligo-Progressive Disease REfractory to Systemic Therapy in Metastatic Cancer

Study Overview
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Brief Summary
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A registry-based randomized phase II trial. A total of 46 patients with metastatic head and neck cancer on systemic therapy with oligoprogression to 1-5 extracranial lesions will be randomized using a 1:1 ratio to standard of care (begin next-line systemic therapy, best supportive care, continue current systemic line, based on treating physician decision) vs. receive stereotactic ablative radiotherapy to all oligoprogressive lesions while continuing their current systemic therapy.

Official Title
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Stereotactic Ablative Radiotherapy for Oligo-Progressive Disease REfractory to Systemic Therapy in Metastatic Cancer: A Phase II Randomized Trial

Conditions
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Head and Neck Cancer, Metastatic Cancer, Oligoprogressive

Intervention / Treatment
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* Other: Standard arm
* Radiation: Experimental arm


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years Biopsy proven HNSCC (oropharynx, oral cavity, nasopharynx, sinonasal, larynx or hypopharynx) Metastatic HNSCC, with pathological or radiological proof of metastasis Ability to provide written informed consent Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Progressive disease while on systemic treatment (any line), defined as per RECIST criteria 1.1 on CT metrics as a greater than 20% increase in the sum measurement of lesions, non-target unequivocal progressive disease or a new lesion on CT. Oligoprogression to 1-5 extracranial lesions ≤ 5cm and involving ≤ 3 organs. Progression at the primary tumor site should be counted within the total of 5 lesions. For patients with lymph node metastases, each node is counted as one site of metastasis. All sites of disease can, in the opinion of the investigator, be safely treated and targetable with SABR (taking into account prior local therapy, organ function and underlying medical condition such as inflammatory bowel disease, pulmonary fibrosis, etc.) Patients with prior metastases that have been treated with ablative therapies (e.g. radiotherapy, surgery or radiofrequency ablation) before their current line of systemic therapy, are eligible. Exclusion Criteria: Pregnancy or breastfeeding Any medical condition that could, in the opinion of the investigator, preclude radiotherapy or prevent follow-up after radiotherapy. Presence of spinal cord compression Metastatic disease that invades the GI tract (including esophagus, stomach, small or large bowel

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized screening phase II trial
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard of care<br>Switch to subsequent systemic therapy line, best supportive care or continue current systemic line | Other: Standard arm<br>* Patients on the standard arm will be treated as per standard of care in our institution. Treatment options could include switching to next systemic therapy line, best supportive care or continuing on current systemic therapy.<br>|
| Experimental: Experimental SABR arm<br>Definitive SABR to oligoprogressive lesions + continue current systemic therapy | Radiation: Experimental arm<br>* SABR to all oligoprogressive lesions + continuation of current systemic therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival | PFS defined from randomization to disease progression at any site or death | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | OS defined as time from randomization to time of death from any cause. | 5 years | 
| Quality of life Measured using the FACT-G tool, head and neck cancer-related patient reported outcome- CTCAE (PRO-CTCAE) and Quality of life 5-level EQ-5D | Measured using the FACT-G tool, lung cancer-related patient reported outcome- CTCAE (PRO-CTCAE) and quality of life 5-level EQ-5D | 5 years | 
| Grade ≥ 3 toxicity Measured using the Common Terminology Criteria for Adverse Events (CTCAE v5.0) | Measured using the Common Terminology Criteria for Adverse Events | 5 years | 
| Local control | Defined as time from the end of SABR treatment to date of local failure and will be measured only in the experimental arm | 5 years | 
| Time to next systemic therapy | Defined as time from randomization to time of subsequent therapy line | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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head and neck cancer, metastatic cancer, oligoprogression