Ablative Therapy for Oligoprogressive Genitourinary Cancers

(LAYOVER 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: 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

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding targeted treatments, known as locally ablative therapies, can benefit individuals with certain genitourinary cancers, such as prostate, urothelial, or renal cell carcinoma, who develop a few new cancer spots despite ongoing treatment. The primary goal is to determine if these additional therapies can delay the need to switch to a different cancer treatment. The study employs specialized techniques, like focused radiation or surgical methods, to directly target the new cancer spots. Suitable candidates are those currently undergoing cancer treatment with a few new cancer areas that can be safely targeted, without requiring an immediate change in their overall treatment plan. As an unphased trial, this study provides a unique opportunity to explore innovative treatments that might enhance current cancer care.

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 treating oligo-progressive genitourinary cancers?

Research has shown that treatments like stereotactic ablative radiotherapy (SABR) and interventional radiology (IR) ablation are generally safe. Studies have found that complications are rare, and most patients tolerate these treatments well. One study specifically noted that using local ablative radiotherapy to target metastatic cancer is a safe option.

These treatments focus on destroying cancer cells in specific areas, which helps protect nearby healthy tissue. While some side effects can occur, they are usually mild and manageable. This evidence suggests that locally ablative therapy is a promising and safe choice for those considering participation in a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about locally ablative therapy for oligoprogressive genitourinary cancers because it offers a targeted approach unlike traditional chemotherapy or systemic treatments. This therapy uses stereotactic ablative radiotherapy (SABR) or interventional radiology (IR) ablation to precisely target and destroy cancer cells, minimizing damage to surrounding healthy tissue. Unlike conventional treatments that affect the whole body, this method focuses directly on the cancer site, potentially reducing side effects and improving recovery times. The precision and localized nature of these treatments hold promise for better outcomes and enhanced quality of life for patients.

What evidence suggests that locally ablative therapy is effective for oligoprogressive genitourinary cancers?

Research has shown that treatments like Stereotactic Ablative Radiotherapy (SABR), which participants in this trial may receive, can effectively delay the need to change overall cancer treatments. Studies have found that SABR benefits individuals with prostate, lung, and kidney cancers by controlling cancer spots that no longer respond to current treatments. Another study found SABR to be a safe and effective local treatment for some gynecological cancers. Overall, these findings suggest that ablative therapies can help manage slowly progressing cancers by targeting specific tumor sites. ^{6 7 8 9 10}

Who Is on the Research Team?

Mamta Parikh

Principal Investigator

University of California, Davis

Are You a Good Fit for This Trial?

This trial is for adults over 18 with certain genitourinary cancers (prostate, bladder, or kidney) that have spread but are limited to 5 new or worsening spots. They must be on a systemic therapy that's been working for at least 3 months and can continue after local treatment. People can't join if they have health issues preventing local therapy or had bad reactions to such treatments before.

Inclusion Criteria

Provision of signed and dated informed consent form

Stated willingness to comply with all study procedures and availability for the duration of the study

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

Exclusion Criteria

I cannot undergo treatments that target specific areas due to my health conditions.

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

My brain tumor is growing.

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

Up to 5 years

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Locally Ablative Therapy

Trial Overview

The study tests the benefit of adding targeted local therapies to ongoing systemic cancer treatments in patients whose cancer has mostly been controlled but started progressing in up to five areas. The main goal is seeing how long patients can go without their treatment failing after this combination.

How Is the Trial Designed?

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+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Local ablative therapy, such as stereotactic body radiotherapy, may effectively treat oligoprogressive disease by targeting specific metastatic sites while allowing patients to continue systemic treatments, which is crucial as resistance to therapies develops.

Current evidence supporting the use of local ablative therapy for oligoprogression is primarily retrospective, highlighting a need for more prospective studies to determine the best management strategies for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Dandelion Dilemma Revisited for Oligoprogression: Treat the Whole Lawn or Weed Selectively? Patel, PH., Palma, D., McDonald, F., et al.[2020]

Focal therapy using high-intensity focused ultrasound for localized prostate cancer resulted in a low rate of genitourinary side effects, with 89% of men maintaining erectile function sufficient for penetration after 12 months.

The treatment showed promising efficacy, with 77% of men biopsied at 6 months having no histological evidence of cancer, and 95% of men showing no evidence of disease on MRI at 12 months, indicating effective cancer control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Focal therapy for localised unifocal and multifocal prostate cancer: a prospective development study. Ahmed, HU., Hindley, RG., Dickinson, L., et al.[2022]

Minimally invasive local ablative therapies, such as cryotherapy and high-intensity focused ultrasound, offer an alternative to traditional radical therapies for men with localized prostate cancer, providing a balance between treatment and quality of life.

These therapies are generally well tolerated with lower side effects compared to surgery or radiation, but their long-term effectiveness in controlling cancer is still uncertain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Minimally invasive ablative therapies for definitive treatment of localized prostate cancer in the primary setting. Lee, EW., Huang, WC.[2021]

In a study of 66 surviving patients with localized prostatic adenocarcinoma, the majority of adverse effects from 2D CT-planned radiation treatment were minor (grade 1) and did not require treatment, with only up to 8% experiencing more severe late effects (grades 2-4).

Sexual function was significantly impacted in 60% of patients who did not receive endocrine treatment, highlighting a notable side effect of the radiation therapy, while major surgical interventions were not necessary for managing complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse effects after radical external beam radiotherapy of localized prostatic adenocarcinoma using two-dimensional dose-planning and a limited field technique. Ljung, G., Häggman, M., Hansson, H., et al.[2019]

Aggressive local therapy combined with androgen deprivation therapy (ADT) shows promise for treating oligometastatic prostate cancer, as evidenced by a study involving 12 patients who received both systemic and local treatments.

The study found significant differences in prostate-specific antigen (PSA) levels between patients who progressed to castration-resistant prostate cancer (CRPC) and those who did not, suggesting that monitoring PSA levels could help predict treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multidisciplinary Therapy in Men with Newly Diagnosed Oligometastatic Prostate Cancer. Watanabe, K., Kawaguchi, G., Ikeda, Y., et al.[2022]

Patients with oligometastatic squamous cell carcinoma of the head and neck, particularly those with a limited number of slowly progressive lesions, may benefit from local ablation techniques like surgical resection or stereotactic body radiotherapy (SABR/SBRT), which can potentially be curative.

Surgical resection remains the preferred treatment based on existing data, but careful consideration of patient and disease-related factors is essential for optimizing treatment strategies, especially in cases of HPV-positive oropharyngeal cancer with late-developing metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oligometastatic Disease Management: Finding the Sweet Spot. Szturz, P., Nevens, D., Vermorken, JB.[2023]

Ablative therapies, such as surgery and stereotactic radiotherapy, show promise in improving progression-free and overall survival in patients with oligometastatic and oligoprogressive non-small cell lung cancer (NSCLC), based on evidence from Phase II trials and retrospective studies.

Ongoing large randomized studies aim to further validate the efficacy of these treatments, while challenges remain in assessing their benefits for oligoprogressive disease and in developing models to guide clinical decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Local Ablative Therapies in Oligometastatic NSCLC: New Data and New Directions. Lang, P., Gomez, DR., Palma, DA.[2021]

In a long-term study of 121 patients with locally advanced prostate cancer treated with radiotherapy alone, 53% experienced local recurrence, with a 5-year recurrence risk of 43% and a 10-year risk of 74%.

Local recurrence was linked to significant morbidity, with 69% of adverse events requiring surgical intervention, including common issues like bladder outlet obstruction and hydronephrosis, indicating that radiotherapy alone may not ensure long-term control of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The frequency and morbidity of local tumor recurrence after definitive radiotherapy for stage C prostate cancer. Holzman, M., Carlton, CE., Scardino, PT.[2019]

Cryoablation of the prostate has evolved into a highly effective and minimally invasive treatment option for localized prostate cancer, particularly for high-risk cases and when other treatments have failed.

This technique is recommended for patients who cannot undergo radical surgery due to contraindications, and its success is supported by standardized procedures and training programs developed over the years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cryoablation of prostate cancer]. Witzsch, UK., Becht, E.[2018]

In a retrospective study of 27 patients with renal cell carcinoma, non-small cell lung cancer, and melanoma undergoing immunotherapy, those who received local ablative treatments after oligoprogression experienced longer progression-free survival and higher response rates.

Patients receiving concurrent radiotherapy had a median survival time of 24.7 months, significantly longer than the 14.5 months for those who did not receive such treatment, suggesting local ablative therapies may enhance the effectiveness of immunotherapy in managing oligoprogression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of local ablative therapies in patients with solid tumors treated with immune checkpoint inhibitors and oligoprogression: a single-center analysis. Ozluk, AA., Karateke, M., Sanli, UA., et al.[2023]

Minimally-invasive ablative therapies like cryotherapy, high intensity focused ultrasound (HIFU), and photodynamic therapy provide effective early cancer control for localized prostate cancer while minimizing side effects, particularly genitourinary morbidity.

These treatments allow for focal therapy, targeting only the cancerous lesions in the prostate, which offers a less aggressive alternative compared to radical therapies and active surveillance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Minimally-invasive technologies in uro-oncology: the role of cryotherapy, HIFU and photodynamic therapy in whole gland and focal therapy of localised prostate cancer. Ahmed, HU., Moore, C., Emberton, M.[2021]

Local treatment for oligometastatic prostate cancer, such as radical prostatectomy or radiation therapy combined with systemic therapy, significantly improves overall survival (16.0% vs. 6.5%) and cancer-specific survival (48.2% vs. 26.3%) compared to nonlocal treatments, based on a meta-analysis of 13 studies with 46,541 patients.

The study also found that local treatment is associated with a higher failure-free survival rate (40.5% vs. 28.4%) and has a low complication rate, indicating that it is both effective and safe for patients with low metastatic burden.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The current role of local treatment in metastatic prostate cancer: systematic review and meta-analysis. Baccaglini, W., Rodrigues, AF., Teles, SB., et al.[2022]

Locally advanced prostate cancer can sometimes be treated with curative intent through local definitive therapy, leading to acceptable long-term cancer control rates for certain patients.

Identifying patients at high risk for tumor recurrence after treatment is crucial for optimizing management strategies in this heterogeneous group of men.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of high-risk populations with locally advanced prostate cancer. Khan, MA., Partin, AW.[2019]

Citations

1.

ascopubs.org

ascopubs.org/doi/10.1200/OA-25-00031

A Phase II Prospective Multicenter Trial

This study suggests that SABR can help delay the need to change systemic therapy in patients with estrogen receptor–positive, human epidermal ...

2.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S016781402400210X

Systematic review of the efficacy of stereotactic ablative ...

SABR appears to have clinical benefit in patients with oligoprogresssive prostate, lung, and renal cancer. Based on the available data, SABR for ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11796838/

The impact of stereotactic ablative radiotherapy on ...

Ablation of oligoprogressive metastases has the potential to control metastatic foci become resistant to the ongoing drug and to delay the ...

4.

clinicaloncologyonline.net

clinicaloncologyonline.net/article/S0936-6555(24)00109-2/fulltext

Treatment Outcomes of Stereotactic Ablative Body ...

This study reported SABR treatment outcomes for multisite OM and OP diseases originating from metastatic breast cancer.

5.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/27870704/

Clinical Outcomes for Stereotactic Ablative Radiotherapy in ...

The SABR is a safe and effective local treatment modality in patients with oligometastatic gynecological disease. Distant progression remains the primary ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06101290

Study Details | NCT06101290 | Locally Ablative TherapY in ...

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- ...

7.

clinicaltrials.gov

clinicaltrials.gov/ct2/show/NCT06103669

Locally AblatiVe TherApy in OLigO-pRogressive SOlid ...

The primary endpoint is disease control at 3 months, defined as continuation in systemic cancer therapy without any changes or permanent discontinuation for 3 ...

8.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9100669/

Local Control after Locally Ablative, Image-Guided ...

Metastases-directed local ablative radiotherapy (aRT) has been shown to be a safe treatment option. In this prospective clinical trial, we ...

9.

journals.lww.com

journals.lww.com/journalppo/Fulltext/2020/03000/Local_Ablative_Therapies_for_Oligometastatic_and.7.aspx?WT.mc_id=HPxADx20100319xMP&generateEpub=Article%7Cjournalppo:2020:03000:00007%7C10.1097/ppo.0000000000000433%7C

Local Ablative Therapies for Oligometastatic and ...

Complication rates after SRS or SBRT are low and suggest that SRT is a safe and well-tolerated treatment. Perhaps the most common and frequently studied ...

10.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11987937/

Treatment Approaches for Oligoprogressive Non-Small Cell ...

Here, we review the current data evaluating the role of radiation in oligoprogressive non-small cell lung cancer (NSCLC) and ongoing trials.