Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Symptoms and General Pathology

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Neoplasm, Residual

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Neoplastic Processes

In part I, 33 patients with metastatic NSCLC with: a) NR-VAF but b) without radiographic progression of disease, will be treated with LAT to determine if ablation to all sites of disease leads to acceptable rates of mean VAF reduction, thus indicating a discernible molecular/clinical response in this subgroup of patients with metastatic disease.

If the appropriate criteria are met in part I,, in part II 60 patients with NR-VAF but without radiographic progression of disease will be randomized to one of two arms: continuation of systemic therapy (standard of care) vs. ablation to all sites of disease (experimental arm), with a primary endpoint of progression free survival.

In part I, 33 patients with metastatic NSCLC with: a) NR-VAF but b) without radiographic progression of disease, will be treated with LAT. In Part II of the study, patients will be randomized to standard of care (continuation of systemic therapy) vs. LAT to all sites of disease

Local ablative therapy

Participants will undergo ctDNA collection in conjunction with their standard of care therapy.

Blood collection to assess for ctDNA

Daniel Gomez, MD

Bob Li, MD

Charles Rutter, MD

Robert Press, MD

The purpose of this study is to see whether receiving local ablative therapy (LAT) when minimal residual disease/MRD levels are rising can reduce MRD levels and control metastatic non-small cell lung cancer/NSCLC longer compared to systemic therapy.

A Study of Local Ablative Therapy (LAT) in People With Non-Small Cell Lung Cancer (NSCLC)

A Phase II Adaptive Study of Local Ablative Therapy (LAT) for Patients With Metastatic Non-Small Cell Lung Cancer (NSCLC) Using Minimal Residual Disease (MRD) as an Integral Biomarker

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

To determine whether Local Ablative Therapy/LAT (ablation to all sites of disease) causes a reduction in mean variant allele frequency/VAF by 6 months after LAT in patients with metastatic NSCLC who have non-responding variant allele frequency/NR-VAF (\<50% reduction in mean VAF) but no radiographic progression of disease. Mean VAF: Mean VAF will be defined by the VAF of each relevant mutation divided by the total number of mutations

PFS will be evaluated through imaging obtained Q3 months +/-2 weeks after enrollment. Progression will be evaluated by RECIST 1.1 guidelines. To determine whether LAT improves PFS in patients with metastatic NSCLC who have NR-VAF but no radiographic progression of disease compared to patients who continue systemic therapy.

Memorial Sloan Kettering Cancer Center

Digestive System Diseases

Disease Progression

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Antineoplastic Agents

All Drugs and Chemicals

Bevacizumab

Antibodies

Cetuximab

Immunoglobulins

Panitumumab

A maximum of three Local ablative therapy (LAT) modalities can be administered for each participant, with a maximum of 2 modalities per organ, provided all LAT can be delivered within 12 weeks and participant can safely resume systemic treatment within 16 weeks from randomisation.

After completing LAT, participant is to resume a further two to three months of first-line systemic treatment to a total of 6 months (including the initial 3-4 months of treatment). For patients receiving a doublet or triplet regimen, treatment may be de-escalated to maintenance fluoropyrimidine +/- biologics or anti-EGFR monotherapy at any point after trial entry at clinician discretion. The treating clinician may choose to discontinue systemic treatment following LAT for patients who have experienced prior intolerable toxicity.

The first-line systemic treatment will be standard of care as determined by the treating clinician. The following standard chemotherapy regimens are allowed: single agent fluoropyrimidine, CAPOX, FOLFOX, FOLFIRI, CAPIRI or FOLFOXIRI. Treatment with a biologic is allowed including bevacizumab or an anti-EGFR antibody (cetuximab or panitumumab). For patients receiving a doublet or triplet regimen, treatment may be de-escalated to maintenance fluoropyrimidine +/- biologics or anti-EGFR monotherapy at any point after trial entry at clinician discretion.

LAT modalities allowed include surgical resection, stereotactic radiotherapy (SRT), laparoscopic or percutaneous thermal ablation \[radiofrequency ablation (RFA) or microwave ablation (MWA)\]. The LAT modalities will be delivered by specialists in the field (surgeons, radiation oncologists and/or interventional radiologists). The precise mode of delivery and number of times the LAT modality is delivered is case-dependent and is determined at a multi-disciplinary meeting (MDM).

Local Ablative Therapy

Standard of care as determined by the treating clinician. The following standard chemotherapy regimens are allowed: single agent fluoropyrimidine, CAPOX, FOLFOX, FOLFIRI, CAPIRI or FOLFOXIRI. Treatment with a biologic is allowed including bevacizumab or an anti-EGFR antibody (cetuximab or panitumumab). For patients receiving a doublet or triplet regimen, treatment may be de-escalated to maintenance fluoropyrimidine +/- biologics or anti-EGFR monotherapy at any point after trial entry at clinician discretion.

Standard first-line systemic treatment

Sukanya Sathyamurthie

Louise Christophersen

Jacqui Mcburnie

Narelle McPhee

Rachel Wong

Karen Matoga

Nadia Ranieri

Marie Luci

Jeanne Tie

Sally Heath

Stephanie Henderson

Nicole Humphreys

This study aims to assess the clinical benefit of local ablative therapy (LAT) following initial standard first-line systemic treatment including the impact on survival, compared to continued standard first-line systemic treatment for oligometastatic colorectal cancer.

Who is this study for:

Adults with unresectable oligo-metastatic colorectal who have demonstrated treatment benefit (partial response or stable disease as per RECIST criteria) after 3-4 months of standard first-line systemic treatment.

Study details

Participants will be randomly allocated to either a LAT arm, who will receive metastasis-directed LAT such as radiotherapy or thermal ablation following initial standard first-line systemic treatment, or a control arm who will receive continued first-line systemic treatment alone. Those receiving LAT will return to systemic treatment 16 weeks post-randomisation. Information on progression-free survival and treatment outcomes will be collected.

Data from this study will inform investigators of the potential benefit of local ablative therapy in the therapeutic setting for metastatic colorectal cancer.

RESOLUTE Trial Aims to Investigate the Value of Adding Local Ablative Treatment to Standard Systemic Treatment for Unresectable Oligometastatic Colorectal Cancer

Randomised Phase II Trial to Evaluate Progression-Free Survival in Integrating Local Ablative Therapy With First-Line Systemic Treatment for Unresectable Oligometastatic Colorectal Cancer

To compare the efficacy of metastasis-directed LAT following initial standard first-line systemic treatment vs continued first-line systemic treatment alone, as measured by Progression-Free Survival (PFS)

To compare the efficacy of LAT following initial standard first-line systemic treatment, compared to continued first-line systemic treatment alone, as measured by Overall Survival (OS)

To compare the efficacy of LAT following initial standard first-line systemic treatment, compared to continued first-line systemic treatment alone, on:

1. time to development of new metastatic lesions.
2. time to initiation of 2nd line systemic treatment.

To assess the time to progression of LAT treated lesions.

To compare systemic treatment-free interval between the two treatment groups.

To assess and compare rate of high-grade (Grade 3-5) toxicities between the two treatment groups.

To compare quality of life measures between the two treatment groups using patient questionnaire - The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) using the 4-point ordinal scale (not at all, a little, quite a bit and very much)

Walter and Eliza Hall Institute of Medical Research

Cancer Council Victoria

Australasian Gastro-Intestinal Trials Group

Osimertinib

Patrick Berkovic, MD

Els Wauters, MD, PhD

Johan Vansteenkiste, MD, PhD

Maarten Lambrecht, MD, PhD

Christel Oyen, RN

To determine whether in patients with EGFR mutated advanced NSCLC and osimertinib as first-line treatment, the (repeated) use of LAT to ≤ 3 OP lesions and continuation of first-line osimertinib, improves the median progression-free survival by more than 3 months (i.e. PFS2-PFS1 = \>3 months).

The (repeated) use of LAT to ≤ 3 OP lesions with continuation of first-line osimertinib, is endorsed by international guidelines (NCCN, ESMO).

In this phase IIb prospective non-randomized observational trial, we want to document the benefit of LAT in this patient cohort.

LAT for Oligoprogressive NSCLC Treated With First-line OSImertinib

Local AblativeTherapy for Oligoprogressive Non-Small-Cell Lung Cancer Treated With First-line OSImertinib

Patterns of disease progression after local ablative therapy (LAT) identified on sequential CT scans taken at 3 monthly intervals to document the natual history of the disease after LAT

Acute and late radiotherapy induced toxicities assessed using the CTCAE v4.0. and the RTOG/EORTC late morbidity score. Acute events are defined as ≤ 90 days post SBRT and late events \> 90 days.

Quality of life is measured by the EORTC QLQ-LC13 questionnaire comprised both of multi-item and single-item measures of lung cancer-associated symptoms (i.e. coughing, haemoptysis, dyspnoea and pain) and side-effects from conventional chemo- and radiotherapy (i.e. hair loss, neuropathy, sore mouth and dysphagia).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Local Ablative Therapy (LAT) in People With Non-Small Cell Lung Cancer (NSCLC)	NCT05429320	Non-small Cell ... Metastatic Non ... Nsclc NSCLC Stage IV Minimal Residua... Non Small Cell ...	Local ablative ... Blood collectio...	18 Years -	Memorial Sloan Kettering Cancer Center
RESOLUTE Trial Aims to Investigate the Value of Adding Local Ablative Treatment to Standard Systemic Treatment for Unresectable Oligometastatic Colorectal Cancer	NCT05862051	Colorectal Canc... Oligometastatic...	Local Ablative ... Standard first-...	18 Years -	Australasian Gastro-Intestinal Trials Group
RESOLUTE Trial Aims to Investigate the Value of Adding Local Ablative Treatment to Standard Systemic Treatment for Unresectable Oligometastatic Colorectal Cancer	NCT05862051	Colorectal Canc... Oligometastatic...	Local Ablative ... Standard first-...	18 Years -	Australasian Gastro-Intestinal Trials Group
A Study of Local Ablative Therapy (LAT) in People With Non-Small Cell Lung Cancer (NSCLC)	NCT05429320	Non-small Cell ... Metastatic Non ... Nsclc NSCLC Stage IV Minimal Residua... Non Small Cell ...	Local ablative ... Blood collectio...	18 Years -	Memorial Sloan Kettering Cancer Center
LAT for Oligoprogressive NSCLC Treated With First-line OSImertinib	NCT04216121	Non-Small Cell ...	Local ablative ... Local ablative ...	18 Years -	Universitaire Ziekenhuizen KU Leuven

Spots Global Cancer Trial Database for local ablative therapy