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

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 the treatment Locally Ablative Therapy for oligoprogressive genitourinary cancers?

Local ablative therapies, like cryotherapy and high-intensity focused ultrasound, have shown promise in treating localized prostate cancer with fewer side effects compared to traditional surgery or radiation. Additionally, local ablative therapy is used in oligoprogressive disease to target specific resistant cancer sites, allowing ongoing systemic treatment with minimal invasiveness and acceptable safety. ^{1 2 3 4 5}

Is ablative therapy generally safe for treating genitourinary cancers?

Ablative therapies like cryotherapy, high-intensity focused ultrasound, and photodynamic therapy are generally well tolerated with minimal side effects, offering a less invasive option compared to traditional treatments for localized prostate cancer. ^{1 6 7 8 9}

How does ablative therapy for oligoprogressive genitourinary cancers differ from other treatments?

Ablative therapy for oligoprogressive genitourinary cancers is unique because it targets only the few cancer sites that have progressed, allowing patients to continue their existing systemic treatments. This approach uses techniques like stereotactic body radiotherapy, which delivers high doses of radiation precisely to the cancerous areas, minimizing damage to surrounding healthy tissue and potentially improving progression-free survival. ^{3 10 11 12 13}

Research Team

Mamta Parikh

Principal Investigator

University of California, Davis

Eligibility Criteria

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

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

Treatment Details

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.

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+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. Egypt pubmed.ncbi.nlm.nih.gov

Minimally invasive ablative therapies for definitive treatment of localized prostate cancer in the primary setting. [2021]

2. England pubmed.ncbi.nlm.nih.gov

The current role of local treatment in metastatic prostate cancer: systematic review and meta-analysis. [2022]

3. England pubmed.ncbi.nlm.nih.gov

The Dandelion Dilemma Revisited for Oligoprogression: Treat the Whole Lawn or Weed Selectively? [2020]

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

Multidisciplinary Therapy in Men with Newly Diagnosed Oligometastatic Prostate Cancer. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Management of high-risk populations with locally advanced prostate cancer. [2019]

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

The frequency and morbidity of local tumor recurrence after definitive radiotherapy for stage C prostate cancer. [2019]

7. England 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. [2019]

8. Germany pubmed.ncbi.nlm.nih.gov

[Cryoablation of prostate cancer]. [2018]

9. Netherlands 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. [2021]

10. England 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. [2023]

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

Focal therapy for localised unifocal and multifocal prostate cancer: a prospective development study. [2022]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Oligometastatic Disease Management: Finding the Sweet Spot. [2023]

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

Local Ablative Therapies in Oligometastatic NSCLC: New Data and New Directions. [2021]