Ablative Therapy for Oligoprogressive Cancer

(VALOROUS Trial)

Overseen by Xiao Zhao, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: University of California, Davis

Must be taking: Systemic therapy

Disqualifiers: Intracranial lesions, others

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This is a phase 2 pragmatic study that evaluates the clinical benefit of continuing systemic therapy with the addition of locally ablative therapies for oligo-progressive solid tumors as the primary objective. The primary outcome measure is the time to treatment failure (defined as time to change in systemic failure or permanent discontinuation of therapy) following locally ablative 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 data supports the effectiveness of this treatment for oligoprogressive cancer?

Research shows that Stereotactic Ablative Radiotherapy (SABR), a precise form of radiation therapy, is effective in controlling tumors in various organs with about 80% success in local control. It has been found to improve survival rates and may even be curative in 20-25% of cases for patients with limited cancer spread, like those with oligoprogressive disease. ^{1 2 3 4 5}

Is ablative therapy for oligoprogressive cancer safe for humans?

Ablative therapy, including Stereotactic Ablative Radiotherapy (SABR), is generally considered safe and non-invasive, with low toxicity, but rare serious complications have been reported. It is important to have strategies in place to reduce these risks. ^{1 3 6 7 8}

How is the treatment for oligoprogressive cancer different from other treatments?

Locally ablative therapy, such as Stereotactic Ablative Radiotherapy (SABR), is unique because it delivers precise, high-dose radiation to tumors in a few sessions, minimizing damage to surrounding healthy tissue. This noninvasive approach is particularly effective for patients with limited metastatic cancer, offering a potential survival benefit and improved local control compared to standard treatments. ^{1 2 3 9 10}

Research Team

Xiao Zhao, MD

Principal Investigator

University of California, Davis

Eligibility Criteria

Adults over 18 with certain cancers (like breast, gynecological, head and neck, sarcomas) who have up to 5 new or worsening metastatic lesions. They must be on systemic therapy they can continue post-treatment and have seen benefits from it for at least 3 months. Not eligible if they have progressing brain tumors or health issues that rule out local therapies.

Inclusion Criteria

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

My cancer spread can be targeted with specific local treatments.

I am 18 years old or older.

Exclusion Criteria

I have side effects from past treatments that prevent me from getting certain local therapies.

My brain tumor is getting worse.

I have health conditions that prevent me from undergoing treatments targeting specific areas.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive systemic therapy with the addition of locally ablative therapies such as 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 after treatment

Up to 5 years

Regular follow-up visits

Treatment Details

Interventions

• Locally ablative therapy (Procedure)

Trial Overview The VALOROUS trial is testing whether adding local ablative treatments (like radiation) to ongoing systemic cancer therapy helps control the disease better in patients whose cancer has started to progress again but only in a limited number of spots.

Participant Groups

Group I: Ablative local therapy Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

University of California, Davis

Lead Sponsor

Trials

958

Recruited

4,816,000+

Rakesh Dixit

University of California, Davis

Chief Executive Officer since 2024

PhD in Biochemistry and Molecular Biology from the University of California, Davis

Suresh Mahabhashyam

University of California, Davis

Chief Medical Officer since 2020

MD from Bangalore Medical College

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

Stereotactic ablative radiotherapy (SABR) is a highly effective and low-toxicity treatment for metastatic tumors, achieving local control rates of about 80%.

SABR shows promise in treating oligometastatic patients, with pilot studies suggesting it may be 'curative' in 20-25% of cases, especially when combined with systemic therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New concepts and insights into the role of radiation therapy in extracranial metastatic disease. Ricardi, U., Filippi, AR., Franco, P.[2013]

This phase II study will evaluate the effectiveness of Stereotactic Ablative Radiotherapy (SABR) combined with ongoing systemic treatment in 68 patients with oligoprogressive Non-Small Cell Lung Cancer (NSCLC), aiming to provide clearer evidence on its benefits compared to standard care.

The study will focus on key outcomes such as progression-free survival and overall survival, while also assessing quality of life and the safety of SABR, addressing a significant gap in current treatment strategies for oligoprogressive NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Ablative Radiotherapy for oligo-progressive disease refractory to systemic therapy in Non-Small Cell Lung Cancer: A registry-based phase II randomized trial (SUPPRESS-NSCLC). Bahig, H., Tonneau, M., Blais, N., et al.[2022]

Stereotactic ablative radiotherapy (SABR) is a promising noninvasive treatment for oligometastatic and oligoprogressive cancer, showing improved progression-free and overall survival in recent randomized trials.

While SABR is generally safe and minimally toxic, there have been rare reports of severe adverse events, highlighting the need for careful patient selection and ongoing research to optimize its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation in the Treatment of Oligometastatic and Oligoprogressive Disease: Rationale, Recent Data, and Research Questions. Zayed, S., Correa, RJM., Palma, DA.[2021]

In a study of 47 patients with oligometastatic non-small cell lung cancer (NSCLC), Stereotactic Ablative Radiotherapy (SABR) demonstrated a median progression-free survival (PFS) of 34.3 months, with even better outcomes (53.9 months) for those achieving a complete metabolic response (CMR).

SABR was well tolerated, with no severe (grade ≥4) toxicities reported, although some patients experienced mild to moderate pneumonitis, indicating that while effective, monitoring for respiratory side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Consolidative stereotactic ablative radiotherapy (SABR) to intrapulmonary lesions is associated with prolonged progression-free survival and overall survival in oligometastatic NSCLC patients: A prospective phase 2 study. Blake-Cerda, M., Lozano-Ruíz, F., Maldonado-Magos, F., et al.[2021]

Stereotactic ablative radiotherapy (SABR) for metastatic lung lesions (MLLs) showed similar local control and overall survival rates compared to SABR for primary lung lesions (PLLs), indicating its efficacy as a treatment option for MLLs.

Patients with MLLs experienced lower long-term toxicities compared to those with PLLs, with a significant predictor for better outcomes being a dose per fraction of 12 Gy or more.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective analysis of stereotactic ablative radiotherapy (SABR) for metastatic lung lesions (MLLs) in comparison with a contemporaneous cohort of primary lung lesions (PLLs). Oskan, F., Dzierma, Y., Wagenpfeil, S., et al.[2020]

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]

In a study of 102 patients treated with stereotactic ablative radiation therapy (SABR) for early-stage non-small-cell lung cancer, a significant correlation was found between higher Biological Equivalent Doses (BED) over 300 Gy and the development of radiological changes such as organizing pneumonia and lung affectation over a 2-year follow-up.

Radiological changes were more pronounced in patients receiving BEDs greater than 300 Gy to healthy lung volumes of at least 30 cc, suggesting that these findings could inform future radiotherapy dose constraints to minimize pulmonary toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biological equivalent dose is associated with radiological toxicity after lung stereotactic ablative radiation therapy. Cases, C., Benegas, M., Sánchez, M., et al.[2023]

Locally ablative therapies, such as stereotactic body radiation therapy (SBRT), are becoming important in treating patients with oligometastatic non-small cell lung cancer (mNSCLC), allowing for precise high-dose treatment in 1 to 5 sessions.

There is strong evidence supporting the use of ablative therapy for oligometastatic NSCLC, particularly for patients with limited metastatic sites and those with oncogene-addicted mNSCLC who are undergoing treatment with tyrosine kinase inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation Therapy for Oligometastatic Non-Small Cell Lung Cancer: Theory and Practice. Rusthoven, CG., Yeh, N., Gaspar, LE.[2015]

Stereotactic ablative body radiotherapy (SABR) is a feasible and well-tolerated treatment for patients with bone-only oligometastatic breast cancer, with 80% of patients successfully receiving treatment and no severe (grade 3 or 4) toxicities reported.

The treatment showed promising efficacy, with a 100% local progression-free survival (LPFS) and 67% distant progression-free survival (DPFS) at two years, suggesting that SABR could be a viable option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic ablative body radiotherapy (SABR) for bone only oligometastatic breast cancer: A prospective clinical trial. David, S., Tan, J., Savas, P., et al.[2020]

References

1. England pubmed.ncbi.nlm.nih.gov

New concepts and insights into the role of radiation therapy in extracranial metastatic disease. [2013]

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

Stereotactic Ablative Radiotherapy for oligo-progressive disease refractory to systemic therapy in Non-Small Cell Lung Cancer: A registry-based phase II randomized trial (SUPPRESS-NSCLC). [2022]

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

Radiation in the Treatment of Oligometastatic and Oligoprogressive Disease: Rationale, Recent Data, and Research Questions. [2021]

4. Ireland pubmed.ncbi.nlm.nih.gov

Consolidative stereotactic ablative radiotherapy (SABR) to intrapulmonary lesions is associated with prolonged progression-free survival and overall survival in oligometastatic NSCLC patients: A prospective phase 2 study. [2021]

5. China pubmed.ncbi.nlm.nih.gov

Retrospective analysis of stereotactic ablative radiotherapy (SABR) for metastatic lung lesions (MLLs) in comparison with a contemporaneous cohort of primary lung lesions (PLLs). [2020]

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

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

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

Biological equivalent dose is associated with radiological toxicity after lung stereotactic ablative radiation therapy. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Hypofractionated image-guided breath-hold SABR (stereotactic ablative body radiotherapy) of liver metastases--clinical results. [2021]

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

Radiation Therapy for Oligometastatic Non-Small Cell Lung Cancer: Theory and Practice. [2015]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Stereotactic ablative body radiotherapy (SABR) for bone only oligometastatic breast cancer: A prospective clinical trial. [2020]