Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Patients will not receive PCI, but will be observed and the same items will be measured as in the PCI-arm.

* 18 fractions of 2Gy
* 12 fractions of 2.5Gy
* 10 fractions of 3 Gy

Prophylactic Cranial Irradiation

Dirk De Ruysscher, MD, PhD

Harry Groen, MD, PhD

For patients with stage III non-small cell lung cancer, which is radically treated, we will investigate whether prophylactic cranial irradiation (PCI) should become standard of care to prevent brain metastases.

For this group of patients, brain metastases are one of the major sites of tumor failure. Radical therapy of symptomatic brain metastases is seldom possible and only very rarely, long term survival can be achieved. PCI has shown to reduce the incidence of brain metastases in patients with non-small cell lung cancer to the same extent as in limited disease small-cell lung cancer. However, the exact value of PCI in stage III NSCLC patient, treated with contemporary chemo-radiation schedule with or without surgery, remains unsettled. Therefore this study is launched, in order to investigate whether PCI should become the standard of care in patients with stage III NSCLC who are treated with curative intention.

Prophylactic Cranial Irradiation (PCI) vs Observation in Stage III NSCLC

Prophylactic Cranial Irradiation (PCI) Versus Observation in Radically Treated Patients With Stage III Non-small Cell Lung Cancer; A Phase III Randomized Study.

University Medical Center Groningen

The Netherlands Cancer Institute

Maastricht Radiation Oncology

Pharmaceutical Solutions

All Drugs and Chemicals

Antineoplastic Agents

Immunomodulating Agents

Cemiplimab

Antineoplastic Agents, Immunological

Cemiplimab IV 350 mg every 3 weeks for up to 12 months or until progression or discontinuation

Placebo (saline solution) IV every 3 weeks for up to 12 months or until progression or discontinuation

Cemiplimab is provided in a 10 ml glass vial

Placebo

EORTC

Dirk de Ruysscher, MD

Frank Aboubakar Nana, MD

This is a multi-center, double-blind, placebo-controlled randomized phase II study to assess whether continuation of cemiplimab treatment (for up to 12 months) increases progression-free survival (PFS) as compared to placebo in patients with a stage IV, synchronous, oligometastatic non-small cell lung cancer (NSCLC) who have not progressed following 4 cycles of cemiplimab with our without platinum-based chemotherapy and radical treatment.

Eligible patients are randomized with a 1:1 ratio to either the cemiplimab or placebo group and will undergo disease assessment (e.g. imaging, blood tests) at regular follow-up visits.

Immunotherapy Consolidation After Radical Treatment of Synchronous Oligo-metastatic NSCLC

FFPE tumour tissue will be collected at diagnosis, at metastasectomy and at progression (if available).

NGS panel, WES (including germline), RNAseq will be used for analysis.

Blood will be collected at registration, at induction (C2D1), after induction, after radical therapy, at consolidation (every 9 weeks from C1D1 (5 times), at end of treatment and at PD.

FFPE tumour tissue and blood will be collected on regular time points during the study.

Analysis will be using multiplex Immuno-Fluorescence (mIF) or other imaging techniques, and/or spatial transcriptomics.

PFS is defined as the time from the date of randomization until first occurrence of any of the following events:

* Disease progression at any site: loco-regional progression/recurrence (related to primary tumour); progression/recurrence of oligometastatic lesions initially present at registration
* Development of new metastatic lesions
* Death due to any cause.

Disease progression will be assessed using the RECIST 1.1 criteria.

OS is defined as the time from the date of randomization until date of death, for any reason

Time to disease progression is defined as the time from the date of randomization to the date of first occurrence of any of the following events:

* Disease progression at any site: loco-regional progression/recurrence (related to primary tumour); progression/recurrence of oligometastatic lesions initially present at registration
* Development of new metastatic lesions
* Death due to progressive disease.

Time to development of new metastatic lesions is the time interval from the date of randomization to the date of first occurrence of any of the following events:

* Development of new metastatic lesions not initially present at registration,
* Death due to progressive disease.

Time to progression in oligometastatic lesions initially present at registration is the time interval from the date of randomization to the date of first progression/recurrence in at least one of the oligometastatic lesions initially present at registration

This study will use the International Common Terminology Criteria for Adverse Events (CTCAE), version 5.0, for adverse event reporting

This questionnaire is composed of 30 individual questions that are scored into 15 multi-item and single-item scales according the EORTC scoring manual. These include five functional scales (physical, role, emotional, social, and cognitive), nine symptom scales (fatigue, nausea and vomiting, pain, dyspnoea, insomnia, appetite loss, constipation, diarrhoea and financial difficulties) and a global health status/QoL scale.

The functional and symptom questions follow the same structure using a 4-point Likert scale with responses from "not at all" to "very much".

The questions on global health an QoL use a 7-point Likert scale with responses from "very poor" to "excellent".

This questionnaire includes self-assessment of treatment side effects, most notable pneumonitis.

The questions follow the same structure using a 4-point Likert scale with responses from "not at all" to "very much" and are scored according to the scale structure of their respective source questionnaire.

This questionnaire includes 8 questions from the EORTC lung cancer specific module (QLQ-LC29) were selected: the coughing domain scale (2 questions), the dyspnoea scale (3 questions), chest pain (1 question) and physical capabilities (1 question).

The questions follow the same structure using a 4-point Likert scale with responses from "not at all" to "very much" and are scored according to the scale structure of their respective source questionnaire.

This questionnaire includes 1 item from the validated QLQ-ELD14 questionnaire to include self-assessment on treatment burden: "How much has your treatment been a burden to you?" The questions follow the same structure using a 4-point Likert scale with responses from "not at all" to "very much" and are scored according to the scale structure of their respective source questionnaire.

European Organisation for Research and Treatment of Cancer - EORTC

Neoplasms, Multiple Primary

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Amino Acids

Etoposide

Gemcitabine

Vinorelbine

Paclitaxel

Carboplatin

Pemetrexed

Albumin-Bound Paclitaxel

Cisplatin

Etoposide phosphate

Mitogens

Afatinib

Tyrosine Kinase Inhibitors

Erlotinib Hydrochloride

Gefitinib

Tyrosine

Patients with synchronous metastases at Central Nervous System (CNS), evaluated in less than one week by the Multidisciplinary Committee at National Cancer Institute of Mexico to define the initial treatment. Patients with metastases at other sites than CNS will receive first line systemic treatment, in those EGFR-mutated with tyrosine kinase inhibitors (TKI) and in patients without a driver mutation with first line duplet of chemotherapy based on platin. The type of TKI or chemotherapy will be at discretion of the treating physician.

After 4 cycles of treatment, patients with stable disease or partial response will be evaluated by de Multidisciplinary Committee to establish the type of radical treatment to the primary and to the metastases, radiation therapy and chemoradiotherapy.

Epidermal growth factor receptor (EGFR)-mutated with tyrosine kinase inhibitors (afatinib, erlotinib or gefitinib). Patients without driver mutation duplet of chemotherapy based on platin taking account histologic subtype (Carboplatin or Cisplatin plus pemetrexed for adenocarcinomas, gemcitabine for epidermoid or paclitaxel for both) at discretion of the treating physician.

First line systemic treatment

to the primary and to the metastases will be with surgery, radiotherapy, chemoradiotherapy, stereotactic radiosurgery or radiofrequency ablation.

Radical treatment

Patients will receive dose and fraction regimen according to the metastatic site.

radiation therapy

Chemoradiotherapy with duplet based on platins (Carboplatin or cisplatin plus pemetrexed or paclitaxel or etoposide or vinorelbine) or monotherapy with carboplatin.

Chemoradiotherapy

Oscar Arrieta, MD

Non-small cell lung cancer (NSCLC) is the most frequent neoplasm worldwide and also represents the main cause of cancer death. However, it represents the main cause of death by cancer. The prognosis of survival at 5 years is poor, approximately 13-15%.

Various studies suggest that patients who clinically present with a limited number of metastases, a term defined as oligometastatic disease, could have a better prognosis of survival with a radical treatment, than for their counterparts with a greater number of metastasis.

The purpose of this study is to add more information to the current medical literature about the benefits in overall survival of radical treatment of oligometastatic disease in patients with NSCLC and equal or less than 5 synchronous metastases at the time of diagnosis.

The outcomes of the study are to determine the global survival and progression-free survival in patients with synchronous oligometastatic (equal to or less than 5 sites) advanced NSCLC undergoing radical treatment of all metastatic sites and the primary tumor.

Non-small cell lung cancer (NSCLC) is the most frequent neoplasm worldwide and also represents the main cause of cancer death. However, it represents the main cause of death by cancer. The prognosis of survival at 5 years is poor, approximately 13-15%.

The timely detection of NSCLC is difficult and the options for curative treatment are limited since the majority of patients are diagnosed in advanced stages. The standard treatment in metastatic disease is cytotoxic chemotherapy with platins (cisplatin or carboplatin) in combination with a third generation drug (vinorelbine, paclitaxel, docetaxel, gemcitabine or pemetrexed). This therapeutic scheme results in response rates between 20-30%, with a mean overall survival between 8-11 months.

In recent years, research in oncology has focused on the development of therapies aimed at molecular targets that control the growth and proliferation of the tumor cell. Various monoclonal antibodies (bevacizumab, cetuximab) and tyrosine kinase inhibitors (erlotinib, gefitinib, afatinib, crizotinib) have been evaluated with this purpose in NSCLC treatment. Clinical studies in advanced NSCLC, using these new drugs with or without chemotherapy, have had favorable results by increasing the progression-free survival and the response rate, without being able to demonstrate to date, a significant improvement in the overall survival.

Various studies suggest that patients who clinically present with a limited number of metastases, a term defined as oligometastatic disease, could have a better prognosis of survival with a radical treatment, than for their counterparts with a greater number of metastasis.

Much of the current medical information on clinical outcomes in oligometastatic disease is based on clinical studies and retrospective case series of institutions. The majority of the reports have included a mix of patients with synchronous and metachronous oligometastatic disease, focusing on the radical treatment of specific sites such as the brain and adrenal glands. These results have been recognized by the European Society for Medical Oncology (ESMO) and have been included in its treatment guidelines for lung cancer (2012). The recommendation states to consider some radical treatment in selected patients with solitary metastases.

There is limited information about the clinical benefits in overall survival in the subgroup of patients with NSCLC that clinically present with synchronous oligometastatic disease and equal to or less than 5 synchronous metastases at the time of diagnosis.

The purpose of this study is to add more information to the current medical literature about the benefits in overall survival of radical treatment of oligometastatic disease in patients with NSCLC and equal to or less than 5 synchronous metastases at the time of diagnosis. The outcomes of the study are to determine the global survival and progression-free survival in patients with synchronous oligometastatic (equal to or less than 5 sites) advanced NSCLC undergoing radical treatment of all metastatic sites and the primary tumor.

First line systemic treatment Epidermal growth factor receptor (EGFR)-mutated with tyrosine kinase inhibitors (afatinib, erlotinib or gefitinib). Patients without driver mutation duplet of chemotherapy based on platin taking account histologic subtype (Carboplatin or Cisplatin plus pemetrexed for adenocarcinomas, gemcitabine for epidermoid or paclitaxel for both) at discretion of the treating physician.

Radical treatment to the primary and to the metastases will be with surgery, radiotherapy, chemoradiotherapy, stereotactic radiosurgery or radiofrequency ablation.

Radiation: radiation therapy Patients will receive dose and fraction regimen according to the metastatic site.

Chemoradiotherapy Chemoradiotherapy with duplet based on platins (Carboplatin or cisplatin plus pemetrexed or paclitaxel or etoposide or vinorelbine) or monotherapy with carboplatin.

Radical Treatment of Synchronous Oligometastatic Non-Small Cell Lung Carcinoma

Radical Treatment of Synchronous Oligometastatic Disease and Primary Tumor in Advanced Non-small Cell Lung Carcinoma (NSCLC)

Time to event as calculated from confirmed histopathological diagnosis of NSCLC up until death or last follow up.

Time to event as calculated from first-line therapy start (any therapy) until documented radiological progression as assessed by PET-CT using RECIST 1.1 criteria.

No evidence of metabolic activity by FDG PET-CT scan

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Prophylactic Cranial Irradiation (PCI) vs Observation in Stage III NSCLC	NCT01282437	Non Small Cell ... Radical Treatme... Stage III Non-S...	Prophylactic Cr...	18 Years -	Maastricht Radiation Oncology
Immunotherapy Consolidation After Radical Treatment of Synchronous Oligo-metastatic NSCLC	NCT06219317	NSCLC Stage IV	Cemiplimab Placebo	18 Years -	European Organisation for Research and Treatment of Cancer - EORTC
Prophylactic Cranial Irradiation (PCI) vs Observation in Stage III NSCLC	NCT01282437	Non Small Cell ... Radical Treatme... Stage III Non-S...	Prophylactic Cr...	18 Years -	Maastricht Radiation Oncology
Radical Treatment of Synchronous Oligometastatic Non-Small Cell Lung Carcinoma	NCT02805530	Carcinoma, Non-... Synchronous Neo...	First line syst... Radical treatme... radiation thera... Chemoradiothera...	18 Years -	Instituto Nacional de Cancerologia de Mexico

Spots Global Cancer Trial Database for radical treatment