Ablative Therapy for Lung Cancer

(OBLITERATE Trial)

Overseen By Selina Laqui, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of California, Davis

Must be taking: Systemic therapy

Disqualifiers: Medical comorbidities, Intracranial lesions, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach for treating lung cancer by adding locally ablative therapies (also known as ablative therapy or locoregional therapy) to ongoing systemic treatment. The aim is to determine if this combination can delay the need to change or stop treatments due to cancer progression. Participants should have a history of lung cancer with a few new or growing tumors and must currently receive systemic therapy that remains mostly effective. The trial employs treatments like precise radiotherapy or special ablation techniques to directly target the tumors. This approach suits those whose tumors can be safely treated with these local methods. As an unphased trial, it offers patients the opportunity to explore innovative treatment combinations that may enhance their current therapy.

Will I have to stop taking my current medications?

The trial does not require you to stop your current medications. You can continue your current systemic therapy, with a possible break of up to 30 days for the local ablative therapy.

What prior data suggests that locally ablative therapy is safe for lung cancer?

Research has shown that treatments like stereotactic ablative radiotherapy (SABR) are promising for lung cancer and have a good safety record. Studies indicate that SABR is effective for lung and chest cancers, though treating tumors in the center of the chest may result in more side effects. Most patients tolerate the treatment well, with manageable side effects.

For instance, one study found no major differences in outcomes between patients treated with SABR for early-stage lung tumors on the outer parts of the lungs and other patients, highlighting the treatment's consistent safety. While there are risks of side effects, they are usually not severe for most patients.

In summary, treatments like SABR are generally safe, and many patients tolerate them well. However, the tumor's location can influence the side effects experienced. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for lung cancer, which often involve surgery, chemotherapy, or conventional radiation, locally ablative therapy offers a more targeted approach. This treatment includes techniques like Stereotactic Ablative Radiotherapy (SABR) and interventional radiology (IR) ablation, which precisely target and destroy cancerous tissue with minimal impact on surrounding healthy tissue. Researchers are excited about these methods because they can potentially reduce side effects and recovery time, and may be effective against tumors that are difficult to reach with traditional methods. This precision-focused approach could lead to better outcomes and improved quality of life for patients.

What evidence suggests that locally ablative therapy is effective for lung cancer?

Research has shown that treatments like stereotactic ablative radiotherapy (SABR), which participants in this trial may receive as part of the ablative local therapy arm, effectively treat lung cancer. Studies have found that SABR works well for patients with early-stage non-small cell lung cancer (NSCLC) by effectively controlling tumors. For example, some studies reported a 0% death rate within 90 days after treatment, highlighting its safety. Other research suggests that SABR is as effective as surgery for early lung tumors. Overall, evidence supports using this type of treatment as a promising way to manage certain lung cancers. ^{1 2 6 7 8}

Who Is on the Research Team?

Megan E. Daly

Principal Investigator

University of California, Davis

Are You a Good Fit for This Trial?

This trial is for adults over 18 with certain lung cancers (non-small or small cell) who've seen benefits from their current cancer treatment but have a few new or worsening spots of cancer. They must be able to undergo local therapies like radiation and continue their systemic therapy with a short break.

Inclusion Criteria

I am willing and able to follow the study rules and attend all appointments.

I've had at least one treatment for my cancer that spread, and it worked for 3 months before the cancer grew.

I am on a systemic therapy plan and can continue it with a short break for a specific treatment.

Exclusion Criteria

I have side effects from past treatments that prevent me from undergoing certain cancer therapies.

My brain tumor is growing.

I have health conditions that prevent me from undergoing targeted cancer treatments.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Ablative Local Therapy

Participants receive stereotactic ablative radiotherapy (SABR) or interventional radiology (IR) ablation therapy

3 months

Visits as per standard practices

Follow-up

Participants are monitored for disease control and adverse events

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Locally Ablative Therapy

Trial Overview The study tests if adding local treatments, such as targeted radiation, to ongoing systemic therapy helps control cancer when only a few areas are getting worse. The main goal is to see how long patients can stay on their current treatment without needing to change it due to the cancer progressing.

How Is the Trial Designed?

Group I: Ablative local therapy Experimental Treatment 1 Intervention

Stereotactic ablative radiotherapy (SABR) or interventional radiology (IR) ablation therapy

Locally Ablative Therapy is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Locally Ablative Therapy for:

• Liver cancer
• Colorectal carcinoma metastases
• Hepatocellular carcinoma
• Neuroendocrine malignancies

Approved in United States as Locally Ablative Therapy for:

• Primary liver cancer
• Metastatic liver cancer
• Hepatocellular carcinoma
• Colorectal carcinoma metastases

Approved in Canada as Locally Ablative Therapy for:

• Liver cancer
• Hepatocellular carcinoma
• Colorectal carcinoma metastases

Who Is Running the Clinical Trial?

University of California, Davis

Lead Sponsor

Trials

958

Recruited

4,816,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 176 patients with oligometastatic lung adenocarcinoma, local ablative radiotherapy (LART) significantly improved progression-free survival (PFS), especially in patients treated with tyrosine kinase inhibitors (TKIs) and those receiving LART at all metastatic sites, with a 1-year PFS of 86.7%.

LART also showed potential in extending survival for patients with repeat oligoprogression by delaying changes in systemic therapy, indicating its role as an effective treatment option in managing oligometastatic disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aggressive Local Ablative Radiotherapy Mitigates Progression Risk in Oligometastatic Lung Adenocarcinoma. Yang, G., Kim, KH., Lee, CG., et al.[2023]

Irreversible electroporation is a promising new ablation technique for treating localized non-small cell lung carcinoma (NSCLC), especially in challenging tumor locations where traditional methods may be less effective.

The review discusses various established and novel ablation methods, highlighting their mechanisms, indications, potential complications, and clinical outcomes, which can guide treatment decisions for NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thermal ablation of stage I non-small cell lung carcinoma. Ridge, CA., Solomon, SB., Thornton, RH.[2021]

Aggressive treatment approaches, including local ablative therapy (LAT) such as radiation and surgery, have shown efficacy and safety in prolonging disease-free and overall survival in select patients with oligometastatic non-small cell lung cancer (NSCLC).

Despite promising results from recent randomized trials, there is still a need for more robust clinical evidence and validated biomarkers to guide treatment decisions for patients with oligometastatic NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Local Ablative Therapy in Oligometastatic NSCLC. Li, X., Gomez, D., Iyengar, P.[2022]

Local ablative therapy, such as surgery, stereotactic radiotherapy, and radiofrequency ablation, has been shown to improve outcomes for patients with oligometastatic and oligoprogressive non-small cell lung cancer (NSCLC).

Historically, treatment for metastatic NSCLC was mainly palliative, but recent evidence over the past 30 years suggests that targeted local treatments can lead to better survival rates and overall patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Local Ablative Therapies for Oligometastatic and Oligoprogressive Non-Small Cell Lung Cancer. Jairam, V., Park, HS., Decker, RH.[2021]

Percutaneous ablation is an effective non-invasive technique for treating metastatic lung tumors, particularly in patients with slowly evolving disease, allowing for multiple local treatments with minimal impact on lung function.

This method has low morbidity and is generally safe, although its effectiveness can be limited by the size and location of the tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Is there a curative treatment for oligometastases? Lung radiofrequency ablation]. Palussière, J., Descat, E., Cornélis, F.[2012]

Lobar resection remains the standard treatment for early-stage non-small cell lung cancer (NSCLC), but sublobar resection (SLR) is being compared as a less invasive alternative for patients with T1N0 NSCLC.

For patients who cannot undergo surgery, options like stereotactic body radiotherapy (SBRT) and various ablation techniques are available, with ongoing research into bronchoscopic methods that leverage existing percutaneous techniques for effective tumor treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Bronchoscopy for Lung Nodules: Where Are We Now? Folch, E., Guo, Y., Senitko, M.[2022]

Image-guided ablative therapies, particularly radiofrequency ablation, are safe and effective for controlling localized lung tumors in patients who cannot undergo surgery due to the extent of their disease or other health issues.

These therapies can slow disease progression and extend disease-free survival, with manageable complications such as pneumothorax and pneumonia, making them a valuable option in lung cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Image-guided percutaneous ablation of lung malignancies: A minimally invasive alternative for nonsurgical patients or unresectable tumors. Chamarthy, MR., Gupta, M., Hughes, TW., et al.[2014]

Transbronchial therapies, particularly microwave ablation, are becoming increasingly important for treating multifocal lung cancers and patients who cannot undergo surgery, reflecting a shift towards more localized and less invasive treatment options.

Innovative adjunct technologies, such as mobile C-arm platforms and robotic bronchoscopy, are enhancing the efficiency and accuracy of transbronchial ablation, which may lead to better outcomes in lung cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transbronchial Techniques for Lung Cancer Treatment: Where Are We Now? Chan, JWY., Siu, ICH., Chang, ATC., et al.[2023]

About 80% of lung cancers are not operable, leading to a need for alternative treatments like local ablation therapy, which offers a promising option for patients with unresectable tumors.

Guidelines have been developed by a multidisciplinary team to standardize thermal ablation procedures, ensuring proper candidate selection, outcome assessment, and complication prevention, which enhances the safety and efficacy of this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expert consensus workshop report: Guidelines for thermal ablation of primary and metastatic lung tumors (2018 edition). Ye, X., Fan, W., Wang, H., et al.[2018]

Lung cancer is the leading cause of death in adults, and while surgical resection is the preferred treatment, many patients cannot undergo surgery due to health issues or limited lung function.

Image ablation techniques, specifically radiofrequency ablation and cryoablation, offer safe alternative treatments for localized lung cancer in selected patients, providing options for those who are not surgical candidates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How I do it: radiofrequency ablation and cryoablation of lung tumors. Sharma, A., Moore, WH., Lanuti, M., et al.[2011]

Local ablative treatment (LAT) significantly improves overall survival (OS) and progression-free survival (PFS) in patients with oligometastatic nonsmall cell lung cancer, with pooled odds ratios showing a 3.49 times higher chance of OS and 3.74 times higher chance of PFS compared to standard care across 20 studies involving 1750 patients.

Sensitivity analyses, including randomized controlled trials, further support LAT's efficacy, showing even greater odds ratios of 4.11 for OS and 4.96 for PFS, indicating that LAT is a beneficial treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of local ablative treatment in oligometastatic non-small cell lung cancer: a meta-analysis. Rim, CH., Cho, WK., Park, S., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5601509/

A systematic review of outcomes following stereotactic ... This systematic review considers the evidence supporting the use of SABR in early-stage NSCLC, reported toxicity rates, the use of SABR in centrally located ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1556086415317287

Outcomes of Stereotactic Ablative Radiotherapy for ... No significant differences in outcomes were observed between these 63 patients and 445 other SABR patients treated for peripheral early-stage lung tumors. Three ...

3. ro-journal.biomedcentral.com ro-journal.biomedcentral.com/articles/10.1186/s13014-023-02286-5

Comparison of outcome after stereotactic ablative ... This is the first study to evaluate the safety and efficacy of SABR for stage I metachronous NSCLC compared to primary lung cancer.

4. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2698079

Outcomes With Salvage Treatment for Recurrence After ... This study provides data on outcomes for patients with recurrence after stereotactic ablative radiotherapy, which may help in clinical decision making.

5. por-journal.com por-journal.com/journals/pathology-and-oncology-research/articles/10.3389/pore.2024.1611709/full

Stereotactic body radiotherapy in lung cancer The overall 90-day mortality was 0% for RTOG 0236, 2.4% for surgery, and 2% for radiofrequency ablation [17]. In a prospective phase 2 study, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7585334/

Long-term Toxicity and Survival Outcomes After Stereotactic ... Stereotactic ablative radiotherapy (SABR) is effective for thoracic cancer and metastases; however, adverse effects are greater for central tumors.

7. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2809582

Individualized Stereotactic Ablative Radiotherapy for Lung ... Findings In this nonrandomized controlled trial of 217 unique patients with 285 treated tumors, rates of freedom from local recurrence at 1 year ...

8. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.868844/full

Safety and Efficacy of Stereotactic Ablative Radiotherapy ... Patients with UCLC can benefit from SBRT at a dose of 56 Gy/6-8f. On the other hand, smaller PTV was associated with superior outcomes.