Stereotactic Ablative Radiotherapy for Metastatic Cancer

(ID-COMET Trial)

Overseen By ASK RPCI

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Roswell Park Cancer Institute

Disqualifiers: Chemotherapy, Radiotherapy, Brain metastases, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

800 Participants Needed

Trial Summary

What is the purpose of this trial?

This protocol is comprised of three unblinded, randomized, single-center studies to evaluate the impact of immediate versus three-month delayed comprehensive ablative treatment on survival in newly diagnosed metastatic patients with lung (Trial 1), colorectal (Trial 2), and prostate (Trial 3) cancers

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, it mentions that participants should not have had chemotherapy or radiotherapy within 3 weeks (or 6 weeks for certain drugs) before entering the study, suggesting a possible need to pause some treatments.

What data supports the effectiveness of the treatment Stereotactic Ablative Radiotherapy for Metastatic Cancer?

Research shows that Stereotactic Body Radiotherapy (SBRT) is effective in controlling tumors in early-stage non-small cell lung cancer and has a good safety profile when used for multiple pulmonary metastases. It is also being used for oligometastatic disease, with ongoing studies to further evaluate its benefits. ^{1 2 3 4 5}

Is Stereotactic Ablative Radiotherapy (SBRT) safe for humans?

Stereotactic Ablative Radiotherapy (SBRT) is generally considered safe for treating various cancers, including lung and liver tumors, with a good safety profile. However, it can cause some side effects like tissue damage, especially near sensitive areas like the bowels and nerves, but these are usually manageable and occur later after treatment. ^{1 2 6 7 8}

How is the treatment Stereotactic Ablative Radiotherapy (SBRT) unique for metastatic cancer?

Stereotactic Ablative Radiotherapy (SBRT) is unique because it delivers high doses of radiation precisely to the tumor while sparing surrounding healthy tissue, making it a noninvasive and convenient outpatient treatment. It is particularly effective for tumors in the lung and liver and offers high rates of tumor eradication with a short treatment course and minimal recovery time. ^{3 8 9 10 11}

Research Team

Anurag Singh, MD

Principal Investigator

Roswell Park Comprehensive Cancer Center

Eligibility Criteria

This trial is for adults with newly diagnosed metastatic lung, colorectal, or prostate cancer. They must be willing to consent, have a life expectancy over 6 months, and an ECOG performance status of ≤3 (still active). Restaging scans should be recent. Those with signs of fibrotic interstitial lung disease need respirologist clearance.

Inclusion Criteria

I can take care of myself but cannot do heavy physical work.

My cancer has spread to other parts of my body.

I am at least 1 year old.

Exclusion Criteria

I have fluid buildup due to cancer in the lining of my lung.

I have serious health issues that prevent me from receiving radiotherapy.

My liver is not working well due to cancer spread.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Immediate Treatment

Participants receive immediate Stereotactic Ablative Radiotherapy (SABR) plus standard of care

3 months

Delayed Treatment

Participants receive SABR after a delay of three months, following standard therapy

3 months

Follow-up

Participants are monitored for survival, quality of life, and radiation-related toxicity

Up to 5 years

Treatment Details

Interventions

• Stereotactic Ablative Radiotherapy

Trial Overview The ID-COMET trial compares immediate versus delayed Stereotactic Ablative Radiotherapy (SABR) in patients with certain types of metastatic cancers. It's unblinded and randomized at one center to see if timing affects survival rates.

Participant Groups

Group I: Trial 4 - Immediate SABR plus standard of care Experimental Treatment 2 Interventions

Group II: Standard Therapy followed by SABR - Trial 1-3 Arm 1 Experimental Treatment 2 Interventions

Group III: SABR plus Standard therapy - Trial 1-3 Arm 2 Experimental Treatment 2 Interventions

Stereotactic Ablative Radiotherapy is already approved in European Union, United States, United Kingdom for the following indications:

Approved in European Union as Stereotactic Ablative Radiotherapy for:

• Early-stage non-small cell lung cancer
• Liver cancers
• Kidney cancers
• Bone metastasis
• Spinal metastasis
• Prostate cancers

Approved in United States as Stereotactic Ablative Radiotherapy for:

• Early-stage non-small cell lung cancer
• Liver cancers
• Kidney cancers
• Bone metastasis
• Spinal metastasis
• Prostate cancers

Approved in United Kingdom as Stereotactic Ablative Radiotherapy for:

• Early-stage non-small cell lung cancer
• Liver cancers
• Kidney cancers
• Bone metastasis
• Spinal metastasis
• Prostate cancers

Who Is Running the Clinical Trial?

Roswell Park Cancer Institute

Lead Sponsor

Trials

427

Recruited

40,500+

Findings from Research

In a study of 145 patients with early-stage non-small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT), the treatment demonstrated a high local control rate with only 24.1% experiencing disease recurrence over a median follow-up of 65.6 months.

SBRT was associated with low toxicity, as only 3.4% of patients experienced grade 3 adverse events, and no patients suffered from severe (grade 4 or 5) toxicities, indicating that it is a safe treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five-year follow-up after stereotactic body radiotherapy for medically inoperable early-stage non-small cell lung cancer: a multicenter study. Guo, Y., Zhu, Y., Zhang, R., et al.[2023]

In a study of 145 patients with multiple pulmonary metastases treated with stereotactic body radiotherapy (SBRT), the overall survival (OS) was 23.5 months, indicating that SBRT is effective for this condition.

The study found no increase in the risk of early death or severe toxicity (grade 4 or 5) associated with multiple SBRT treatments, suggesting a strong safety profile for this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy (SBRT) for multiple pulmonary oligometastases: Analysis of number and timing of repeat SBRT as impact factors on treatment safety and efficacy. Klement, RJ., Hoerner-Rieber, J., Adebahr, S., et al.[2018]

In a study of 40 patients with EGFR wild-type oligometastatic non-small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT), the median overall survival was 40 months, indicating that SBRT can be an effective treatment option for this patient group.

The study found that high-dose radiation (BED10 ≥100 Gy) was associated with better progression-free survival compared to lower doses, and the treatment was well-tolerated, with no severe toxicities reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing efficacy and safety of stereotactic body radiation therapy for oligometastatic non-small cell lung cancer with epidermal growth factor receptor (EGFR) wild type. Hu, X., Li, H., Liu, H., et al.[2022]

Stereotactic body radiotherapy (SBRT) is effective for treating stage I lung cancer, achieving local control rates similar to those of surgical resection while minimizing side effects to surrounding healthy tissues.

SBRT is being explored for treating oligometastatic disease, although current evidence of its clinical benefits is limited; ongoing international studies aim to clarify its effectiveness and potential combinations with other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy for oligometastatic disease. Hanna, GG., Landau, D.[2018]

Stereotactic body radiotherapy (SBRT) is an effective treatment for patients with stage I non-small cell lung cancer (NSCLC) who cannot undergo surgery, with a median overall survival of 30 months for T1 tumors and 26 months for T2 tumors based on a study of 723 patients.

Higher biological equivalent doses (BED10) of SBRT significantly improve local control rates for T2 tumors, with a local failure rate dropping from 32% to 8% as the BED10 increases from <105 Gy to ≥150 Gy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy for early-stage non-small cell lung cancer: clinical outcomes from a National Patient Registry. Davis, JN., Medbery, C., Sharma, S., et al.[2022]

A 68-year-old woman treated with stereotactic body radiation therapy (SBRT) for lung metastases experienced pathological vertebral fractures ten months post-treatment, highlighting a previously unreported adverse effect of SBRT.

Despite achieving a complete response of the metastatic disease without signs of radiation pneumonitis, the case emphasizes the need for oncologists to consider the risk of bone toxicity, particularly in older patients with potential low bone mineral density (BMD).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pathological vertebral fracture after stereotactic body radiation therapy for lung metastases. Case report and literature review. Rodríguez-Ruiz, ME., San Miguel, I., Gil-Bazo, I., et al.[2022]

Stereotactic body radiotherapy (SBRT) for ultra-central lung tumors shows high efficacy, with pooled local control rates of 92% at 1 year and 89% at 2 years, based on a systematic review of 27 studies involving 1183 treated targets.

While SBRT is effective, it carries risks of severe toxicity, with a 6% incidence of grade 3-4 toxicities and a 4% incidence of treatment-related deaths, highlighting the importance of careful patient selection and treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy for Ultra-Central lung Tumors: A systematic review and Meta-Analysis and International Stereotactic Radiosurgery Society practice guidelines. Yan, M., Louie, AV., Kotecha, R., et al.[2023]

Stereotactic body radiation therapy (SBRT) is a highly effective, noninvasive treatment for tumors, particularly in the lung and liver, offering high rates of tumor eradication with minimal recovery time required for patients.

While SBRT has a favorable overall toxicity profile, it can lead to delayed side effects such as ulceration and fibrosis, especially when treating tumors near sensitive structures like the bowel, highlighting the need for careful patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emergence of stereotactic body radiation therapy and its impact on current and future clinical practice. Timmerman, RD., Herman, J., Cho, LC.[2022]

Stereotactic body radiation therapy (SBRT) is an effective treatment for early-stage non-small cell lung cancer (NSCLC), providing precisely targeted radiation doses to tumors, especially for patients who cannot undergo surgery.

The review highlights the importance of SBRT in both medically inoperable cases and its potential role in operable early-stage NSCLC, indicating its growing significance in cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Body Radiation Therapy for Early-Stage Lung Cancer. Maquilan, G., Timmerman, R.[2018]

Stereotactic body radiation therapy (SBRT) for metastatic lung tumors showed promising long-term outcomes, with 1-, 3-, and 5-year local control rates of 88.8%, 75.4%, and 75.4%, respectively, based on a study of 71 patients with 172 lesions.

The treatment was well-tolerated, with no severe toxicities reported, and only one patient experiencing a non-symptomatic rib fracture, suggesting SBRT is a safe alternative to surgery for certain patients with lung metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiation therapy favors long-term overall survival in patients with lung metastases: five-year experience of a single-institution. Zhang, Y., Xiao, JP., Zhang, HZ., et al.[2022]

Stereotactic body radiation therapy (SBRT) is a preferred treatment for early-stage non-small cell lung cancer (NSCLC) patients who cannot undergo surgery, but accurate lymph node staging is crucial for optimal patient selection.

Current staging methods like PET/CT and EBUS have limited sensitivity in detecting lymph node metastases, which can lead to undetected cancer spread and poorer outcomes; thus, invasive staging procedures are often necessary to improve detection and potentially enhance survival with adjuvant therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Undetected lymph node metastases in presumed early stage NSCLC SABR patients. Cerra-Franco, A., Diab, K., Lautenschlaeger, T.[2017]

References

1. China pubmed.ncbi.nlm.nih.gov

Five-year follow-up after stereotactic body radiotherapy for medically inoperable early-stage non-small cell lung cancer: a multicenter study. [2023]

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

Stereotactic body radiotherapy (SBRT) for multiple pulmonary oligometastases: Analysis of number and timing of repeat SBRT as impact factors on treatment safety and efficacy. [2018]

3. China pubmed.ncbi.nlm.nih.gov

Assessing efficacy and safety of stereotactic body radiation therapy for oligometastatic non-small cell lung cancer with epidermal growth factor receptor (EGFR) wild type. [2022]

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

Stereotactic body radiotherapy for oligometastatic disease. [2018]

5. Germany pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy for early-stage non-small cell lung cancer: clinical outcomes from a National Patient Registry. [2022]

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

Pathological vertebral fracture after stereotactic body radiation therapy for lung metastases. Case report and literature review. [2022]

7. Ireland pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy for Ultra-Central lung Tumors: A systematic review and Meta-Analysis and International Stereotactic Radiosurgery Society practice guidelines. [2023]

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

Emergence of stereotactic body radiation therapy and its impact on current and future clinical practice. [2022]

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

Stereotactic Body Radiation Therapy for Early-Stage Lung Cancer. [2018]

10. China pubmed.ncbi.nlm.nih.gov

Stereotactic body radiation therapy favors long-term overall survival in patients with lung metastases: five-year experience of a single-institution. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Undetected lymph node metastases in presumed early stage NSCLC SABR patients. [2017]