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Transformation Into Small Cell Lung Cancer : a Mode of Resistance to Treatment (TransCPC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03419286
Recruitment Status : Completed
First Posted : February 1, 2018
Last Update Posted : February 1, 2018
Sponsor:
Information provided by (Responsible Party):
University Hospital, Grenoble

Brief Summary:
The discovery of oncogenic mutations and the use of targeted therapies have transformed the management of certain tumors. Thus 12 to 15% of bronchial adenocarcinomas (AD) carry mutations of EGFR and receive from the first line inhibitors of this kinase (ITK). Despite spectacular results, relapse and resistance are quasi-general phenomena. In most known cases, EGFR-TKI resistance mechanisms involve secondary mutations of EGFR or the activation of alternative oncogenic pathways. However, in 5 to 15% of patients, resistance is manifested by the emergence of a small cell carcinoma (CPC), a cancer of neuroendocrine origin very different from AD by its cellular, molecular and epidemiological characteristics. This phenotypic transformation is an almost unique phenomenon in oncology and its molecular bases are not understood. To study this phenomenon, a Franco-Italian network was established that documented and collected cases of this rare tumor. This series is the subject of detailed anatomopathological, clinical and therapeutic documentation. This project aims to investigate the exome of one or more matched lesion regions to evaluate the evolutionary processes leading from the initial AD to the relapsing CPC. These results will guide future research on predictive markers of relapse and their targeted treatment.

Condition or disease
Small Cell Lung Cancer

Detailed Description:

An international multicentric retrospective collection of cases was performed between 2005 and 2017. A global e-mailing to a network of thoracic oncology centers in France and Italy called for the selection of retrospective cases. Consecutive non small cell lung cancer (NSCLC) patients with stage III or IV EGFR NSCLC with or without initial EGFR mutation with a secondary transformation to small cell lung cancer (SCLC) in participating centers in France and Italy were included. Patients with a previous history of SCLC or neuroendocrine tumor of the lung were excluded as well as patients with combined Small cell/ Non-small cell lung cancer on the initial pathology sample.

Study ethics approval was obtained on December 8th of 2015 (CECIC Rhône-Alpes-Auvergne, Clermont-Ferrand, IRB 5891). Anonymized data were collected at each center then centrally analyzed at the Albert Bonniot Institute, Inserm U 823, Grenoble Alpes University, in Grenoble, France.

The primary objective of this study was to analyze survival data after transformation to SCLC. The secondary objectives were to define: the epidemiological characteristics at the time of diagnosis of NSCLC, the histomolecular characteristics at the time of diagnosis of NSCLC and at the time of diagnosis of SCLC; the clinical characteristics at the time of diagnosis of NSCLC and SCLC and the treatment characteristics before and after transformation from NSCLC to SCLC.

All identified cases will be analyzed. This concerns about sixty two patients because the transformation into small cell lung cancer is a rare mechanism of resistance, it is for this reason that all the cases will be included in order to obtain the most exhaustive data possible.

Continuous variables were described as median (25%-75% interquartile range [IQR]) and categorical variables as number (%). Associations between categorical variables were compared using the chi-2 test or Fisher's exact test and those between continuous variables using the Wilcoxon test. Patients were followed until November of 2017. Overall survival (OS) is the time from the initial diagnosis of lung cancer to death and survival after SCLC transformation is from the rebiopsy to death. Kaplan-Meier plots of survival curves were compared between groups using the log-rank test. All tests were two-sided, and P values <0.05 were considered statistically significant. All statistical analyses were performed using SAS 9.3 (SAS Institute, Cary, NC, USA).

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Study Type : Observational
Actual Enrollment : 62 participants
Observational Model: Case-Only
Time Perspective: Retrospective
Official Title: Retrospective Study of Cases of Small Cell Lung Cancer (SCLC) That Appeared During Treatment of Another Lung Carcinoma With or Without Oncogenic Activation (TransCPC)
Actual Study Start Date : February 2016
Actual Primary Completion Date : November 2017
Actual Study Completion Date : November 2017

Resource links provided by the National Library of Medicine


Group/Cohort
EGFR MUTATED
patient with lung cancer with EGFR mutation before transformation into small cell lung cancer
EGFR NON MUTATED
patient with lung cancer without driver oncogenic before transformation into small cell lung cancer



Primary Outcome Measures :
  1. survival time after transformation to small cell lung cancer (SCLC) [ Time Frame: 2005 to 2017 ]
    months of survival after transformation into small cell lung cancer


Secondary Outcome Measures :
  1. time from initial diagnosis of non small cell lung cancer (NSCLC) to small cell lung cancer transformation [ Time Frame: 2005 to 2017 ]
    median of months between initial diagnosis of non small cell lung cancer and small cell lung cancer transformation

  2. histology type at the time of diagnosis of NSCLC and at the time of diagnosis of small cell lung cancer (SCLC) [ Time Frame: 2005 to 2017 ]
    histology on biopsy at the initial diagnosis and at transformation according with OMS classification

  3. type of specific treatments administered before and after transformation from non small cell lung cancer into small cell lung cancer [ Time Frame: 2005 to 2017 ]
    The type of treatment administered before and after SCLC transformation. percentage of patients in each type of specific treatment used

  4. sexe of patients [ Time Frame: 2005 to 2017 ]
    sexe female or male in percentage of patients

  5. stage of NSCLC at initial diagnosis [ Time Frame: 2005 to 2017 ]
    percentage of patients with stage III and with IV of NSCLC

  6. smocking status at diagnosis initial of non small cell lung cancer [ Time Frame: 2005 to 2017 ]
    percentage of patients in never, former or active smokers

  7. type of mutations at the diagnostic initial NSCLC and at transformation [ Time Frame: 2005 to 2017 ]
    the mutation on initial biopsy and on biopsy at transformation in SCLC in percentage of patients

  8. treatment lines before transformation into small cell lung cancer (SCLC) [ Time Frame: 2005 to 2017 ]
    Median number of lines of treatment for the NSCLC before transformation into SCLC

  9. response rates to first line treatment after transformation into small cell lung cancer [ Time Frame: 2005 to 2017 ]
    response rate in percentage of patients after transformation into SCLC according with the RECIST criteria

  10. lines of treatment after transformation into SCLC [ Time Frame: 2005 to 2017 ]
    median number of lines of treatment after transformation into SCLC

  11. age of patients [ Time Frame: 2005 to 2017 ]
    the median in years at the he diagnosis initial of non small cell lung cancer



Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
All cases diagnosed between 2005 to 2017 in France and in Italy who respond at the eligibility criteria were included. they are patients with non small cell lung cancer with or without EGFR mutation at the initial diagnosis transformed into small cell lung cancer during treatment of non small cell lung cancer
Criteria

Inclusion Criteria:

  • Patient with no history of small cell cancer or Neuroendocrine cancer
  • Patients with non-small cell lung cancer at baseline, stage IIIB or IV
  • Transformation during treatment of non small cell lung cancer, in small cell cancer proven by biopsy

Exclusion Criteria:

  • History of small cell cancer or Neuroendocrine cancer
  • Absence of histological evidence of the transformation into small cell lung cancer after treatment of non small cell lung cancer
  • Patients with non-small cell lung cancer at initial biopsy, stage I, II, IIIA

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03419286


Sponsors and Collaborators
University Hospital, Grenoble
Investigators
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Principal Investigator: Denis Moro-Sibilot, MD-PHD University Hospital, Grenoble
Publications:

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Responsible Party: University Hospital, Grenoble
ClinicalTrials.gov Identifier: NCT03419286    
Other Study ID Numbers: 38RC16.053
First Posted: February 1, 2018    Key Record Dates
Last Update Posted: February 1, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lung Neoplasms
Small Cell Lung Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms