Stereotactic vs Palliative Radiotherapy for Cancer

Overseen By Narsis Afghari, MSc.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: British Columbia Cancer Agency

Disqualifiers: Serious comorbidities, Malignant effusion, Brain metastasis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 6 weeks

194 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are on systemic therapy, you must have been on it for at least 3 months with a stable or positive response before joining the trial.

What data supports the effectiveness of the treatment Stereotactic ablative radiotherapy (SABR) for cancer?

Research shows that SABR is effective in controlling cancer spread and improving symptoms in patients with metastases, with 88% of symptomatic patients experiencing improvement. It is also associated with high local control rates and low toxicity in early-stage lung cancer, making it a promising option for patients who cannot undergo surgery. ^{1 2 3 4 5}

Is stereotactic ablative radiotherapy (SABR) generally safe for humans?

Stereotactic ablative radiotherapy (SABR) is generally considered safe for treating various cancers, with high rates of local control and low levels of acute and late toxicity reported for peripheral lung cancers. However, for central lung tumors, very high doses can lead to significant toxicity, and strategies are in place to reduce these risks. ^{4 6 7 8 9}

How does the treatment Stereotactic Ablative Radiotherapy (SABR) differ from other treatments for cancer?

Stereotactic Ablative Radiotherapy (SABR) is unique because it delivers very high doses of radiation precisely to the tumor in a few sessions, minimizing damage to surrounding healthy tissue. This makes it particularly effective for treating small, well-defined tumors and offers a non-surgical option for patients who cannot undergo surgery. ^{1 4 10 11 12}

Eligibility Criteria

This trial is for individuals with metastatic cancer showing limited progression (1-5 lesions). Participants must be eligible for radiotherapy and have not received prior SABR or palliative radiation to the oligoprogressive sites. They should be able to undergo MRI scans, provide informed consent, and meet other health criteria.

Inclusion Criteria

Negative urine pregnancy test for People of Child-Bearing Potential (POCBP) within 4 weeks of radiotherapy start date

Restaging completed within 12 weeks prior to randomization

Able to provide informed consent

Exclusion Criteria

My liver cancer is in a critical area.

My liver is not working well due to cancer spread.

I have health conditions that prevent me from receiving radiotherapy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either SABR or palliative conventional radiotherapy to all sites of oligoprogression

6 weeks

Follow-up

Participants are monitored for safety, effectiveness, and quality of life after treatment

60 months

Regular visits at 3, 6, 12, 15, 18, 21, 24, 36, 42, 48, 54, and 60 months

Treatment Details

Interventions

• Palliative radiotherapy
• Stereotactic ablative radiotherapy (SABR)

Trial Overview The STOP-2 trial compares Stereotactic Ablative Radiotherapy (SABR) against conventional Palliative Radiotherapy in patients with a few progressing cancer spots. It's double-blind, meaning neither participants nor researchers know who gets which treatment. The goal is to see if SABR improves survival without disease worsening and quality of life.

Participant Groups

Group I: Experimental Arm (SABR) Experimental Treatment 1 Intervention

Group II: Control Arm (Palliative Radiotherapy) Active Control 1 Intervention

Who Is Running the Clinical Trial?

British Columbia Cancer Agency

Lead Sponsor

Trials

181

Recruited

95,900+

Findings from Research

Stereotactic ablative radiation therapy (SABR) for stage I lung cancer at Sheba Medical Center showed a median overall survival of 46 months and a 3-year survival rate of 59%, indicating its efficacy as a treatment for inoperable patients.

The treatment demonstrated excellent local control at 88% and had manageable toxicity, with only 8.4% of patients experiencing chest wall pain and a low incidence of severe side effects, suggesting it is a safe option for patients with early-stage lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Ablative Body Radiation for Stage I Lung Cancer in Israel: A Retrospective Single-Center Report. Appel, S., Lawrence, YR., Goldstein, J., et al.[2022]

Stereotactic ablative radiotherapy (SABR) has rapidly expanded in clinical use for treating various primary and metastatic tumors, demonstrating promising results in tumor control.

Despite its effectiveness, SABR can lead to serious complications, highlighting the need for strategies to reduce these risks and improve the safety of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serious complications associated with stereotactic ablative radiotherapy and strategies to mitigate the risk. Lo, SS., Sahgal, A., Chang, EL., et al.[2018]

Stereotactic ablative radiotherapy (SABR) demonstrated a high local control rate of 91.2% for skeletal metastases in a study of 22 patients, with a median follow-up of 15.6 months, indicating its effectiveness in managing oligometastatic and oligoprogressive diseases.

The treatment resulted in significant pain control for two-thirds of symptomatic patients, with limited toxicities reported, including only two vertebral fractures and one case of grade 3 esophagitis, suggesting that SABR is a safe option for patients with skeletal metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Utilization of stereotactic ablative radiotherapy in oligometastatic & oligoprogressive skeletal metastases: Results and pattern of failure. Kam, TY., Chan, OSH., Hung, AWM., et al.[2019]

In a study of 40 patients with central and ultracentral non-small cell lung cancer (NSCLC) treated with stereotactic ablative radiotherapy (SABR), those with ultracentral tumors experienced worse overall survival (OS) and progression-free survival (PFS) compared to those with central tumors, indicating a need for careful consideration in treatment planning.

The incidence of severe treatment-related toxicities (grade ≥3) was higher in the ultracentral group, with 12.5% of patients experiencing significant complications, including severe bronchial obstruction and esophageal perforation, highlighting the potential risks associated with SABR in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcomes in patients with central and ultracentral non-small cell lung cancer treated with stereotactic body radiotherapy: single-institution experience. Song, X., Zhao, L., Jiang, N., et al.[2023]

A consensus document was created by trial management groups from six UK studies on stereotactic ablative radiotherapy (SABR) to establish updated organ at risk dose constraints, enhancing safety during treatment.

This unified approach aims to standardize the implementation of SABR across the UK, enabling better comparisons of toxicity and efficacy between different SABR studies both nationally and internationally.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

UK Consensus on Normal Tissue Dose Constraints for Stereotactic Radiotherapy. Hanna, GG., Murray, L., Patel, R., et al.[2022]

Stereotactic ablative radiotherapy (SABR) is a promising treatment option for extracranial tumors, demonstrating both safety and effectiveness when applied with strict adherence to technical guidelines.

The treatment has a very narrow therapeutic window, meaning precise delivery is crucial for maximizing its benefits while minimizing risks to surrounding healthy tissue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Technical know-how in stereotactic ablative radiotherapy (SABR). Lo, SS., Foote, M., Siva, S., et al.[2022]

In a study of 100 patients with early-stage non-small cell lung cancer (NSCLC) treated with stereotactic ablative body radiotherapy (SABR), the 1-, 2-, and 3-year local control rates were 100%, 93.55%, and 84.33%, respectively, indicating high efficacy in tumor control.

The treatment was associated with low toxicity, with only 2% of patients experiencing Grade-3 side effects, suggesting that SABR is a safe option for patients who are inoperable or refuse surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Definitive Treatment of Early-Stage Non-Small Cell Lung Cancer with Stereotactic Ablative Body Radiotherapy in a Community Cancer Center Setting. Heal, C., Ding, W., Lamond, J., et al.[2020]

Stereotactic ablative radiation therapy (SABR) was found to be effective for treating pulmonary metastases, with a median follow-up of 23 months showing improved overall survival (OS) for patients with 3 or fewer metastases compared to those with more (74.2% vs. 59.3% at 24 months).

Patients with less responsive primary tumors (like adrenal or pancreatic cancers) had higher local failure rates, suggesting that higher doses of SABR or surgical options may be necessary for these cases to improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiation therapy for pulmonary metastases: Improving overall survival and identifying subgroups at high risk of local failure. Pasalic, D., Lu, Y., Betancourt-Cuellar, SL., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Stereotactic ablative body radiotherapy (SABR) for effective palliation of metastases: factors affecting local control. [2020]

2. Ireland pubmed.ncbi.nlm.nih.gov

Outcomes of stereotactic ablative radiotherapy for central lung tumours: a systematic review. [2022]

3. Israel pubmed.ncbi.nlm.nih.gov

Stereotactic Ablative Body Radiation for Stage I Lung Cancer in Israel: A Retrospective Single-Center Report. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Stereotactic ablative body radiotherapy for lung cancer. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Stereotactic Ablative Radiotherapy Uncertainties: Delineation, Setup and Motion. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Serious complications associated with stereotactic ablative radiotherapy and strategies to mitigate the risk. [2018]

7. Australia pubmed.ncbi.nlm.nih.gov

Utilization of stereotactic ablative radiotherapy in oligometastatic & oligoprogressive skeletal metastases: Results and pattern of failure. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Long-term outcomes in patients with central and ultracentral non-small cell lung cancer treated with stereotactic body radiotherapy: single-institution experience. [2023]

9. England pubmed.ncbi.nlm.nih.gov

UK Consensus on Normal Tissue Dose Constraints for Stereotactic Radiotherapy. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Technical know-how in stereotactic ablative radiotherapy (SABR). [2022]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Definitive Treatment of Early-Stage Non-Small Cell Lung Cancer with Stereotactic Ablative Body Radiotherapy in a Community Cancer Center Setting. [2020]

12. Ireland pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiation therapy for pulmonary metastases: Improving overall survival and identifying subgroups at high risk of local failure. [2021]