Brief Summary

Advancements in systemic antineoplastic therapies have led to improved overall survival rates for many solid tumors. However, metastatic disease remains a significant challenge and remains the leading cause of mortality for these patients. Additionally, there is a high attrition rate after first-line standard treatment across various tumor types, with studies indicating that 20-70% of patients may be unable to undergo second-line therapy, depending on the tumor type. This highlights an urgent need to enhance outcomes from the first line of treatment. Although first-line therapy often represents the best available option, most patients experience relapse and disease progression despite an initial tumor response. This is attributed to both intrinsic and acquired resistance arising from the heterogeneity of primary tumors and metastases. To address this issue, metastasis-directed therapy (MDT) has been explored as a way to reduce tumor burden and mitigate the risk of resistance due to therapeutic selective pressure. MDT offers a promising opportunity to improve first-line treatment outcomes, but more precise patient selection criteria are needed to maximize therapeutic benefit and minimize the potential toxicity of ablative therapies. Indeed, despites its efficacy, fatal complication may occur so do grade 3 to 4 toxicities. Toxicity depends of the local ablative therapy (LAT) planned but as it will never be none, oncologists have to propose invasive treatment to patient that may benefit the most. Based on the published data, the investigators propose a pragmatic, selective approach centered on sensitivity to systemic therapy. The investigators aim to evaluate the benefit of local ablative therapy (LAT) in patients who demonstrate non-progressive disease after three months of first-line standard of care. Given the importance of this question across cancer subtypes, the investigators will employ a prospective database to enroll patients with various solid tumor type, excluding the ones for which the impact of LAT has already been explored or may be difficult to achieve. Outcomes of this strategy will be evaluated compared to outcomes from pivotal studies defining optimal standard first line therapy (OST) . Several analyses will be performed to better characterize the population for whom a multimodal approach may significantly improve their survival. The first one will aim to compare the median duration of response (mDOR) of the population treated with LAT compared to the mDOR reported by the pivotal study(ies) of each OST. This study will serve as a proof of concept, supporting chemosensitivity as a viable selection factor for multimodal treatment in a broad range of cancer types. Primary objective: Improvement of the duration of response (DOR) after completion of LAT compared to DOR reported in pivotal study that evaluated first line OST. Secondary objectives:

Evaluation of the safety of the addition of LAT.
Evaluation of overall progression free survival (PFS) and PFS at 1 year.
Evaluation of overall survival from OST start and from the time of LAT completion.
Documentation of acceptance and compliance to LAT decision by the institutional expert committee

Trial Health

Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

1,235

participants targeted

Target at P75+ for all trials

Timeline

122mo left

Started Jun 2026

Longer than P75 for all trials

Geographic Reach

5 countries

12 active sites

Status

not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

10 years study duration

First Submitted

Initial submission to the registry

April 10, 2026

Completed

12 days until next milestone

First Posted

Study publicly available on registry

April 22, 2026

Completed

1 month until next milestone

Study Start

First participant enrolled

June 1, 2026

Expected

7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2033

3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2036

Last Updated

April 22, 2026

Status Verified

April 1, 2026

Enrollment Period

7 years

First QC Date

April 10, 2026

Last Update Submit

April 21, 2026

Conditions

Solid Tumor

Outcome Measures

Primary Outcomes (1)

Duration of response after completion of LAT (DORLAT)
DORLAT is defined by the time between end of local ablative therapy and disease progression (according to RECIST 1.1 criteria) or death, depending of which happen first.
From end of local ablative therapy to disease progression or death, depending of which happen first and up to 5 years.

Secondary Outcomes (4)

Adverse event count
From the time of LAT decision to up to 6 months after LAT and subsequent OST administration
Overall Survival OST
From OST start to death of the patient and up to 5 years
Overall Survival LAT
From LAT completion to death of the patient and up to 5 years
Progression free survival
From OST start to first disease progression and up to 5 years

Study Arms (17)

HR+ HER2- breast cancer

Hormone receptor positive, HER2 negative breast cancer treated by CDK4/6 inhibitor and endocrine therapy