STOP-2 is a phase III multi-institutional double-blind randomized trial. 194 participants will be enrolled in this trial. Participants will be randomized in a 1:1 ratio between the Control Arm vs. the Experimental Arm. Participants, enrolling oncologists, and the statistician will be blinded to trial arm assignment. In the control arm, radiotherapy will consist of 8 Gy in 1 fraction to all sites of oligoprogression, and the experimental arm will consist of SABR treatment to all sites of oligoprogression. Primary Objectives * To assess the impact of SABR, compared to palliative conventional radiotherapy, on Progression-free survival on next line systemic therapy (PFS-NEST), oncologic outcomes, and Quality of Life (QOL) in participants with 1-5 oligoprogressing lesions. * To assess the feasibility of the clinical trial in terms of accrual and success of double-blinding. Secondary Objectives * To evaluate and compare the impact of SABR and palliative radiation therapy on the overall survival (OS), progression free survival (PFS), polymetastatic progression-free survival (PPFS); * To assess and compare the proportion of participants receiving additional radiation therapy and other metastasis-directed interventions during follow-up between both arms; * To compare the impact of SABR and palliative radiation therapy on the time to initiation of the next line of systemic therapy; * To identify and compare the anatomic sites of disease progression between the experimental (SABR) and control (palliative radiation) arms; * To compare the treatment related toxicity among participants in each arm; * To evaluate and compare the quality of life among participants in each arm; * To assess the cost-effectiveness of the experimental arm compared to the control arm.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
194
SABR is a safe and effective modality for metastasis-directed therapy, delivering a high dose of radiotherapy to a small target using conformal techniques. Emerging evidence suggests that SABR for oligoprogressive cancer may extend the duration of systemic therapy, and result in improvements in Progression Free Survival (PFS) and Overall Survival (OS) compared to historic controls.
Radiotherapy will consist of 8 Gy in 1 fraction to all sites of oligoprogression. Participants will continue their current systemic therapy (if already on systemic therapy at the time of oligoprogression event) or continue off systemic therapy (if the participant was not on systemic therapy at the time of the oligorecurrence event).
BC Cancer - Surrey
Surrey, British Columbia, Canada
RECRUITINGProgression-Free Survival on Next Line Systemic Therapy (PFS-NEST)
Time from randomization to progression (RECIST criteria) beyond next line of systemic therapy or death from any cause or date of last follow-up, whichever occurs first. Next line systemic therapy is the first new systemic therapy initiated after documented disease progression
Time frame: 3 months, 6 months, 12 months, 15 months, 18 months, 21 months, 24 months, 36 months, 42 months, 48 months, 54 months, 60 months
Evaluation of feasibility of the clinical trial in terms of successful accrual
Accrual will be measured by the number of participants enrolled in the trial within the specified time frame.
Time frame: 12 and 24 months
Evaluation of feasibility of the clinical trial in terms of success of double-blinding
The success of double-blinding will be measured by providing both the participant and oncologist with a blinding questionnaire asking them to select the suspected trial arm assignment (options include palliative arm, SABR arm, or unknown).
Time frame: 6 weeks
Evaluation of OS, PFS, and PPFS
To evaluate and compare the impact of SABR and palliative radiation therapy on the overall survival (OS), progression free survival (PFS), polymetastatic progression-free survival (PPFS);
Time frame: 3 months, 6 months, 12 months, 15 months, 18 months, 21 months, 24 months, 36 months, 42 months, 48 months, 54 months, 60 months
Time to next line systemic therapy
To assess and compare the proportion of participants receiving additional radiation therapy and other metastasis-directed interventions during follow-up between both arms;
Time frame: 3 months, 6 months, 12 months, 15 months, 18 months, 21 months, 24 months, 36 months, 42 months, 48 months, 54 months, 60 months
Comparing the anatomic sites of disease progression
A list of anatomical sites at which there are new or progressing lesions will be collected
Time frame: 3 months, 6 months, 12 months, 15 months, 18 months, 21 months, 24 months, 36 months, 42 months, 48 months, 54 months, 60 months
Evaluation of the treatment related toxicities
Assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 5 for each organ treated (e.g., liver, lung, bone)
Time frame: 3 months, 6 months, 12 months, 15 months, 18 months, 21 months, 24 months, 36 months, 42 months, 48 months, 54 months, 60 months
Comparing the quality of life among participants in each arm using Functional Assessment of Cancer Therapy: General (FACT-G)
Quality of life will be assessed with the FACT-G questionnaire. The FACT-G score ranges from 0 to 108, with higher scores indicating a better quality of life.
Time frame: 3 months, 6 months, 12 months, 15 months, 18 months, 21 months, 24 months, 36 months, 42 months, 48 months, 54 months, 60 months
Comparing the quality of life among participants in each arm using EuroQol 5-Dimension 5-Level (EQ-5D-5L)
Quality of life will be assessed with the EQ-5D-5L questionnaire. The EQ-5D-5L index score ranges from -0.224 to 1, with higher scores indicating a better quality of life.
Time frame: 3 months, 6 months, 12 months, 15 months, 18 months, 21 months, 24 months, 36 months, 42 months, 48 months, 54 months, 60 months
Comparing cost-effectiveness of the arms using the resource utilization forms
Costs associated with each treatment arm will be measured using resource utilization forms.
Time frame: 3 months, 6 months, 12 months, 15 months, 18 months, 21 months, 24 months, 36 months, 42 months, 48 months, 54 months, 60 months
Comparing cost-effectiveness of the arms using the EQ-5D-5L
Costs associated with each treatment arm will be measured using EQ-5D-5L
Time frame: 3 months, 6 months, 12 months, 15 months, 18 months, 21 months, 24 months, 36 months, 42 months, 48 months, 54 months, 60 months
Evaluation of Tumor Response Rate (TRR) using RECIST Criteria
Tumor response rate will be assessed using RECIST criteria.
Time frame: 3 months, 6 months, 12 months, 15 months, 18 months, 21 months, 24 months, 36 months, 42 months, 48 months, 54 months, 60 months
Evaluation of Quality of Life (QOL) using European Organization For Research And Treatment Of Cancer (EORTC QLQ-C30) Questionnaire
Health-related quality of life will be measured using the EORTC QLQ-C30 questionnaire, covering physical functioning, emotional functioning, and symptom scales. This questionnaire consists of 30 items, and the score range is 0-100. On this scale, a higher score indicates a higher (better) level of functioning or a higher (worse) level of symptoms, depending on the type of scale.
Time frame: 3 months, 6 months, 12 months, 15 months, 18 months, 21 months, 24 months, 36 months, 42 months, 48 months, 54 months, 60 months
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