Ablative Therapy of Oligometastatic Tumor After Response to Conventional First Line Treatment (ATOM-1st)

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

Study Overview

• Status: Not yet recruiting
• Conditions: Solid Tumor
• Intervention / Treatment: Other: Data extraction from medical files

• Study Type: Observational
• Enrollment (Estimated): 1235

Contacts and Locations

• Study Contact: Name: Ahmad Awada, MD; Phone Number: +32 2 434 52 11; Email: Ahmad.Awada.Onco@chirec.be

Study Locations

• Belgium
  • Brussels, Belgium, 1020
    • CHU Brugmann
    • Contact: Peter VUYLSTEKE, MD; Phone Number: 3224772158; Email: peter.vuylsteke@chu-brugmann.be
    • Contact: Marianne Paesmans; Phone Number: 3224773306; Email: marianne.paesmans@chu-brugmann.be
    • Principal Investigator: Peter VUYLSTEKE, MD
  • Brussels, Belgium, 1200
    • Cliniques Universitaires Saint-luc
    • Principal Investigator: François DUHOUX, MD
    • Contact: François DUHOUX, MD; Phone Number: +3227645435; Email: francois.duhoux@saintluc.uclouvain.be
    • Contact: Jean Pascal MACHIELS; Phone Number: + 32 2 764 19 92; Email: jean-pascal.machiels@saintluc.uclouvain.be
  • Brussels, Belgium, 1160
    • CHIREC Hospital
    • Principal Investigator: Ahmad Awada, MD
    • Contact: Ahmad Awada, MD; Phone Number: +32 2 434 52 11; Email: Ahmad.Awada.Onco@chirec.be
  • Charleroi, Belgium, 6000
    • Grand Hopital de Charleroi, site Notre Dame
    • Contact: Jean-Luc Canon; Phone Number: +32 60 11 12 24; Email: jean-luc.canon@ghdc.be
    • Contact: David Schroeder; Phone Number: +32 60 11 12 25; Email: david.schroeder@ghdc.be
  • Mons, Belgium, 7000
    • HELORA Hôpital de Mons - Site Kennedy
    • Contact: Stéphane Holbrechts, MD; Phone Number: +32 65 41 37 46; Email: stephane.holbrechts@helora.be
    • Principal Investigator: Stéphane Holbrechts, MD
• Cyprus
  • Nicosia, Cyprus, 2006
    • Bank of Cyprus Oncology
    • Contact: Demetris PAPAMICHAEL, MD
    • Principal Investigator: Demetris PAPAMICHAEL, MD
• France
  • Caen, France, 14000
    • Centre de Lutte Contre le Cancer François Baclesse
    • Contact: François CHERIFI, MD
    • Principal Investigator: François CHERIFI, MD
  • Marseille, France, 13009
    • Institut Paoli-Calmettes
    • Contact: Anthony GONCALVES, MD
    • Principal Investigator: Anthony GONCALVES, MD
  • Saint-Priest-en-Jarez, France, 42270
    • CHU de Saint-Etienne
    • Contact: Simon NANNINI, MD
    • Principal Investigator: Simon NANNINI, MD
  • Strasbourg, France, 67200
    • Hôpital Universitaire de Strasbourg
    • Principal Investigator: Philippe BARTHELEMY, MD
    • Contact: Philippe BARTHELEMY, MD
• Lebanon
  • Beirut, Lebanon
    • American University of Beirut (AUB)
    • Contact: Ali SHAMSEDDINE, MD
    • Principal Investigator: Ali SHAMSEDDINE, MD
• Norway
  • Oslo, Norway
    • Oslo University Hospital / The Norwegian Radium Hospital
    • Contact: Jon AMUND KYTE; Email: jonky@ous-hf.no
    • Principal Investigator: Jon AMUND KYTE, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with non-progressive disease after at least 3 months of optimal standard first line therapy (OST) defined according to ESMO guidelines. The OST is defined as the up-to-date most efficient first systemic line in term of anti-tumoral activity and survival benefit for each tumor type according to the ESMO guidelines and national practice. All cancer sites (including primitive lesion if concerned) must be accessible for local ablative treatment (LAT) based on radiological assessment of less than 6 weeks and LAT must have been decided by the investigator's local multidisciplinary team before inclusion in the study.

Description

Inclusion Criteria:

1. Performance status 0 or 1 on the Eastern Cooperative Oncology Group (ECOG).

2. Histologically diagnosis of one of these tumour types:

   1. Hormone receptor positive, HER2 negative breast cancer
   2. Triple negative breast cancer
   3. HER2+ breast cancer
   4. Non small cell lung cancer without oncogenic addiction
   5. Head and Neck squamous cell carcinoma without recurrence in the radiation field
   6. Gastric adenocarcinoma
   7. Esophageal cancer (adenocarcinoma or epidermoid carcinoma)
   8. Recurrent pancreatic cancer without local recurrence
   9. Anal cancer
   10. Bladder cancer
   11. Clear cells renal cell carcinoma
   12. Prostate cancer sensitive to castration
   13. Adenocarcinoma endometrial cancer
   14. Epidermoid carcinoma or adenocarcinoma of the cervix
   15. Colorectal cancer
   16. Recurrent Soft Tissue Sarcoma
   17. Melanoma
3. Patient with a decision by the local team to give OST and effective administration of OST. OST is defined as the most efficient choice in terms of survival in first line of advanced disease according to ESMO or other international guidelines. In case of multiple choice as first line, if no data provided direct evidence of superiority from one or the other options, there are all considered as OST. If the patient received a less efficient treatment because of his comorbidity or frailty, the eligible criteria won't be fulfilled.

4. Have non-progressive disease after 3 to 6 months of treatment, and less than 6 weeks before presentation to the multidisciplinary team

   1. Patients with complete response and no target lesion are excluded.
   2. Patients with bone metastasis with remaining bone condensation or scare from tumoral activity may be eligible depending on metabolic activity of the lesion or local multidisciplinary committee decision concerning the risk of residual disease.
5. After 3 to 6 months of treatment, and less than 6 weeks before start of LAT, patient must have an oligometastatic disease defined as all lesions (including primitive lesion) amenable to local ablative treatment according to local investigator team and respective local committee.

Exclusion Criteria:

1. Patients who already received systemic antitumoral treatment in the advanced setting (including chemotherapy, immunotherapy, targeted therapy, …)
2. Patients without OST administration
3. Patients that have progressing lesion at any time point before decision of LAT by the expert committee
4. Has a known recent history of other invasive tumour, excepted if local investigator may provide histologically data that all active lesions targeted are from the same cancer primitive.
5. Radiotherapy or other LAT to any metastatic site before the start of OST.
6. Exclusion criteria specific for France: Vulnerable persons according to the article L.1121-6 of the public health law (CSP), adults who are the subject of a measure of legal protection or unable to express their consent according to article L.1121-8 of the CSP

Study Plan

How is the study designed?

Number of groups / cohorts

17

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
HR+ HER2- breast cancer; Hormone receptor positive, HER2 negative breast cancer treated by CDK4/6 inhibitor and endocrine therapy	Other: Data extraction from medical files; Data extraction from medical files
Triple negative breast cancer; Triple negative breast cancer treated by association of pembrolizumab and chemotherapy or standard first line chemotherapy (paclitaxel, epirubicin +/- cyclophosphamide, carboplatine + gemcitabine).	Other: Data extraction from medical files; Data extraction from medical files
HER2+ breast cancer; HER2 positive breast cancer treated by dual blockade HER2 and taxane	Other: Data extraction from medical files; Data extraction from medical files
NSCLC; Non-small cell lung cancer (NSCLC) without usual oncogenic addiction treated by chemotherapy and immunotherapy or immunotherapy alone if indicated.	Other: Data extraction from medical files; Data extraction from medical files
Gastric adenocarcinoma; Gastric adenocarcinoma without local recurrence and treated by 5FU-based chemotherapy combined with immune checkpoint inhibitor (ICI) and/or Trastuzumab if indicated	Other: Data extraction from medical files; Data extraction from medical files
Oesophageal cancer; Oesophageal cancer without local recurrence treated by 5FU-based chemotherapy +/- ICI	Other: Data extraction from medical files; Data extraction from medical files
Pancreatic cancer; Pancreatic cancer without local recurrence treated by FOLFIRINOX or Gemcitabine + Nab-Paclitaxel	Other: Data extraction from medical files; Data extraction from medical files
Anal cancer; Anal cancer treated by carboplatin + paclitaxel or modified DCF	Other: Data extraction from medical files; Data extraction from medical files
Bladder cancer; Bladder cancer treated by platin based chemotherapy or Enfortumab Vedotin + Pembrolizumab	Other: Data extraction from medical files; Data extraction from medical files
Prostate cancer; Metastatic prostate cancer sensitive to castration treated by first and second generation of hormonotherapy	Other: Data extraction from medical files; Data extraction from medical files
Renal cell carcinoma; Renal cell carcinoma treated by ICI combined with ICI or tyrosine kinase inhibitor of VEGFR	Other: Data extraction from medical files; Data extraction from medical files
Endometrial cancer; Endometrial cancer treated by carboplatin + paclitaxel + dostarlimab	Other: Data extraction from medical files; Data extraction from medical files
Cervical cancer; Cervical cancer treated by platin + paclitaxel + bevacizumab + pembrolizumab	Other: Data extraction from medical files; Data extraction from medical files
HNSCC; Head and neck squamous cells carcinoma (HNSCC) without recurrence in the radiation field, treated by chemotherapy and immunotherapy or immunotherapy alone	Other: Data extraction from medical files; Data extraction from medical files
Colorectal cancer; Colorectal cancer treated by 5FU based chemotherapy and targeted therapy (bevacizumab or cetuximab or panitumumab)	Other: Data extraction from medical files; Data extraction from medical files
Soft tissue sarcomas; Soft tissue sarcomas already locally operated and treated by doxorubicin alone every three weeks or in association with ifosfamide or trabectedin.	Other: Data extraction from medical files; Data extraction from medical files
Melanoma; Melanoma treated by ICI or by BRAF/MEK inhibitors	Other: Data extraction from medical files; Data extraction from medical files

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse event count	Clinical and laboratory adverse events (AEs) and serious adverse events (SAEs) will be reported and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0.	From the time of LAT decision to up to 6 months after LAT and subsequent OST administration
Overall Survival OST	Overall Survival defined by the time between OST start and death of the patient	From OST start to death of the patient and up to 5 years
Overall Survival LAT	Overall Survival is defined by the time between LAT completion and death of the patient	From LAT completion to death of the patient and up to 5 years
Progression free survival	Progression free survival is defined by the time between OST start and first disease progression	From OST start to first disease progression and up to 5 years

Collaborators and Investigators

• Sponsor: Chirec
• Collaborators: Oncodistinct; CHU Brugmann, Brussels

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2033
• Study Completion (Estimated): June 1, 2036

Study Registration Dates

• First Submitted: April 10, 2026
• First Submitted That Met QC Criteria: April 21, 2026
• First Posted (Actual): April 22, 2026

Study Record Updates

• Last Update Posted (Actual): April 22, 2026
• Last Update Submitted That Met QC Criteria: April 21, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: ATOM-1st

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No