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Trial record 10 of 331 for:    "Adenocarcinoma of lung"

Chemoresistance and Involvement of the NOTCH Pathway in Patients With Lung Adenocarcinoma (NOTCH)

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ClinicalTrials.gov Identifier: NCT02898857
Recruitment Status : Unknown
Verified August 2016 by University Hospital, Montpellier.
Recruitment status was:  Recruiting
First Posted : September 13, 2016
Last Update Posted : September 13, 2016
Sponsor:
Collaborator:
Institut de Recherche en Cancérologie de Montpellier (IRCM)
Information provided by (Responsible Party):
University Hospital, Montpellier

Brief Summary:
Every year in France, 30.000 deaths are due to lung cancer and 39.500 new cases of this disease are diagnosed (INCa 2014). Patients suffering from locally advanced non-small-cell lung cancer (NSCLC), stage IIIa, usually undergo a multimodality treatment including chemotherapy with platinum compounds before surgery (called neoadjuvant chemotherapy or induction chemotherapy). The reason of this combined modality treatment is the really poor prognosis of patients presenting a disease already spread to lymph nodes (classified N2 when the lymph node under the carina is affected). Up till now, the five-year survival of patients who underwent surgical resection of N2 NSCLC does not exceed 15%

Condition or disease Intervention/treatment
Lung Adenocarcinoma Other: biopsies

Detailed Description:

Every year in France, 30.000 deaths are due to lung cancer and 39.500 new cases of this disease are diagnosed (INCa 2014). Patients suffering from locally advanced non-small-cell lung cancer (NSCLC), stage IIIa, usually undergo a multimodality treatment including chemotherapy with platinum compounds before surgery (called neoadjuvant chemotherapy or induction chemotherapy). The reason of this combined modality treatment is the really poor prognosis of patients presenting a disease already spread to lymph nodes (classified N2 when the lymph node under the carina is affected). Up till now, the five-year survival of patients who underwent surgical resection of N2 NSCLC does not exceed 15%.

NOTCH pathway seems to be implicated in the resistance of tumor to chemotherapy. It is known that NOTCH plays a role in the homeostasis of adult stem cells and of cancer stem cells, including intestine cancer and NSCLC. In breast cancer, it has been demonstrated that NOTCH 1 plays a role in the relapse and adding a treatment by an inhibitor of NOTCH decreases the recurrence rate. An activation of the NOTCH pathway was proven in human lung cancer cell lines (A549 and H460) treated with cisplatin. Furthermore, HES1 (Hairy enhance of split), a downstream gene resulting from NOTCH transcription, was upregulated in patient with relapse comparing resistant versus non-resistant adenocarcinoma NSCLC patients. It was proved, NOTCH pathway is associated with overall survival in NSCLC. Recently, it was showed that an inhibitor of NOTCH combined with chemotherapy strongly potentiates the anti-tumor effects of the systemic therapy. Therefore, one can hypothesize that platinum compound-induced NOTCH activation contributes to the resistance of NSCLC and beyond this point, to tumor progression.


Study Type : Observational
Estimated Enrollment : 18 participants
Time Perspective: Retrospective
Official Title: CHEMO RESISTANCE TO PLATINUM COMPOUNDS AND NOTCH PATHWAYS IN PATIENTS RECEIVING NEOADJUVANT CHEMOTHRERAPY FOR LOCALLY ADVANCED ADENOCARCINOMA OF THE LUNG.
Study Start Date : September 2016
Estimated Primary Completion Date : September 2017
Estimated Study Completion Date : December 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Biopsy Lung Cancer

Group/Cohort Intervention/treatment
down-staging of a KRAS
Six with demonstrated down-staging of a KRAS mutant adenocarcinoma who underwent biopsie The biopsies of lung tumour samples will be analysed by immunochemistry (IHC), western blotting and qPolymerase Chain Reaction (PCR) approaches
Other: biopsies
The biopsies of lung tumour samples will be analysed by immunochemistry (IHC), western blotting and qPolymerase Chain Reaction (PCR) approaches in Six with demonstrated down-staging of a KRAS mutant adenocarcinoma, Six with demonstrated no down-staging (persistent tumour cell involving lymph nodes in surgically resected specimens) of a KRAS mutant adenocarcinoma and Six with or without non-staging and triple negative adenocarcinoma

no down-staging of a KRAS
Six with demonstrated no down-staging (persistent tumour cell involving lymph nodes in surgically resected specimens) of a KRAS mutant adenocarcinoma who underwent biopsie The biopsies of lung tumour samples will be analysed by immunochemistry (IHC), western blotting and qPolymerase Chain Reaction (PCR) approaches
Other: biopsies
The biopsies of lung tumour samples will be analysed by immunochemistry (IHC), western blotting and qPolymerase Chain Reaction (PCR) approaches in Six with demonstrated down-staging of a KRAS mutant adenocarcinoma, Six with demonstrated no down-staging (persistent tumour cell involving lymph nodes in surgically resected specimens) of a KRAS mutant adenocarcinoma and Six with or without non-staging and triple negative adenocarcinoma

non-staging and triple negative adenocarcinoma
Six with or without non-staging and triple negative adenocarcinoma who underwent biopsie The biopsies of lung tumour samples will be analysed by immunochemistry (IHC), western blotting and qPolymerase Chain Reaction (PCR) approaches
Other: biopsies
The biopsies of lung tumour samples will be analysed by immunochemistry (IHC), western blotting and qPolymerase Chain Reaction (PCR) approaches in Six with demonstrated down-staging of a KRAS mutant adenocarcinoma, Six with demonstrated no down-staging (persistent tumour cell involving lymph nodes in surgically resected specimens) of a KRAS mutant adenocarcinoma and Six with or without non-staging and triple negative adenocarcinoma




Primary Outcome Measures :
  1. analysed by immunochemistry (IHC) [ Time Frame: 1 day ]
    The biopsies of lung tumour samples will be analysed by immunochemistry (IHC)


Secondary Outcome Measures :
  1. western blotting (WB) [ Time Frame: 1 day ]
    The biopsies of lung tumour samples will be analysed by western blotting (WB)

  2. qPolymerase Chain Reaction (PCR) [ Time Frame: 1 day ]
    The biopsies of lung tumour samples will be analysed by qPolymerase Chain Reaction (PCR)



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
  • Six with demonstrated down-staging of a KRAS mutant adenocarcinoma
  • Six with demonstrated no down-staging (persistent tumour cell involving lymph nodes in surgically resected specimens) of a KRAS mutant adenocarcinoma
  • Six with or without non-staging and triple negative adenocarcinoma
Criteria

Inclusion Criteria:

patients of both sex, aged 75 years or younger, diagnostic specimen demonstrating an adenocarcinoma, KRAS mutation on exon 2 and codon 12 or codon 13 or triple negative, clinical pathological N2, having received a platinum-based regimen as first line therapy, at less three courses of chemotherapy must have been delivered, with only these molecules : cisplatin-vinorelbine, cisplatin-gemcitabine, cisplatin-docetaxel, cisplatin-paclitaxel, having been operated upon and having been surgically resected R0 or R1.

Exclusion Criteria:

patients having received more than one line of preoperative chemotherapy, having received concurrent chemo-radiotherapy as preoperative treatment, no available diagnostic specimen, patients who underwent R2 resection or no resection, patients affected by adenocarcinoma harbouring either EGFR mutation or EML4-ALK translocation, patients with pathological complete response (yT0yN0).


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): NCT02898857


Contacts
Contact: Jean Louis PUJOL, MD, PhD 4 67 33 61 35 ext 33 jl-pujol@chu-montpellier.fr
Contact: Camille TRAVERT 4 67 33 61 35 ext 33 jl-pujol@chu-montpellier.fr

Locations
France
PUJOL Recruiting
Montpellier, France, 34290
Sponsors and Collaborators
University Hospital, Montpellier
Institut de Recherche en Cancérologie de Montpellier (IRCM)
Investigators
Study Director: Jean Louis PUJOL, MD, PhD University Hospital, Montpellier

Responsible Party: University Hospital, Montpellier
ClinicalTrials.gov Identifier: NCT02898857     History of Changes
Other Study ID Numbers: 9758
First Posted: September 13, 2016    Key Record Dates
Last Update Posted: September 13, 2016
Last Verified: August 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Additional relevant MeSH terms:
Adenocarcinoma
Lung Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases