Lung AdenocarcinomaNOTCHNCT02898857
Chemoresistance and Involvement of the NOTCH Pathway in Patients With Lung Adenocarcinoma
An observational study of Lung Adenocarcinoma, run by University Hospital, Montpellier at 1 site in France.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Lung Adenocarcinoma
- What is being tested?
- biopsies
- How many people
- 18 participants
- Where
- 1 siteFrance
- Study dates
- Sep 2016to Dec 2017
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Who may be able to join
- 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.
Who cannot join
- 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).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: CHEMO RESISTANCE TO PLATINUM COMPOUNDS AND NOTCH PATHWAYS IN PATIENTS RECEIVING NEOADJUVANT CHEMOTHRERAPY FOR LOCALLY ADVANCED ADENOCARCINOMA OF THE LUNG.
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%
Read the 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.
- Conditions
- Lung Adenocarcinoma
- Being tested
- biopsies
- Medical subject headings
- Adenocarcinoma of Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
biopsiesOther
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
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Other: biopsies | |
| 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 Receives: Other: biopsies | |
| 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 Receives: Other: biopsies |
What is being measured
The primary outcome is the main question the study is designed to answer.
analysed by immunochemistry (IHC)
The biopsies of lung tumour samples will be analysed by immunochemistry (IHC)
Measured: 1 day
Secondary outcomes (2)
western blotting (WB)
The biopsies of lung tumour samples will be analysed by western blotting (WB)
Measured: 1 day
qPolymerase Chain Reaction (PCR)
The biopsies of lung tumour samples will be analysed by qPolymerase Chain Reaction (PCR)
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2016 (estimated)
- Study startSep 2016
- Primary completionSep 2017 (estimated)
- Study completionDec 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lung AdenocarcinomaStudies of the same condition, open and under way.
- More trials run by University Hospital, MontpellierThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Time perspective
- Retrospective
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Montpellier
- Sponsor type
- University, hospital or other
- Collaborators
- Institut de Recherche en Cancérologie de Montpellier (IRCM)
- Responsible party
- Sponsor
- Investigators
- Jean Louis PUJOL, MD, PhD, Study director, University Hospital, Montpellier
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02898857
- Sponsor's protocol ID
- 9758
- Acronym
- NOTCH
- Status last verified
- Aug 2016
- First submitted
- 8 Sep 2016
- Last updated
- 13 Sep 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 13 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CHEMO RESISTANCE TO PLATINUM COMPOUNDS AND NOTCH PATHWAYS IN PATIENTS RECEIVING NEOADJUVANT CHEMOTHRERAPY FOR LOCALLY ADVANCED ADENOCARCINOMA OF THE LUNG.
- ClinicalTrials.gov ID
- NCT02898857
- Acronym / sponsor ID
- NOTCH / 9758
- Conditions
- Lung Adenocarcinoma
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- University Hospital, MontpellierUniversity, hospital or other
- Collaborators
- Institut de Recherche en Cancérologie de Montpellier (IRCM)
- Study start
- Sep 2016
- Primary completion
- Sep 2017 (estimated)
- Study completion
- Dec 2017 (estimated)
- First posted
- 13 Sep 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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%
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 design
- Time perspective
- Retrospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| down-staging of a KRAS | – | Other: biopsiesSix 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 |
| no down-staging of a KRAS | – | Other: biopsiesSix 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 |
| non-staging and triple negative adenocarcinoma | – | Other: biopsiesSix 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 |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (1 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| biopsiesThe 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 | Other | down-staging of a KRAS, no down-staging of a KRAS, non-staging and triple negative adenocarcinoma |
Primary outcome
analysed by immunochemistry (IHC)
Time frame: 1 day
The biopsies of lung tumour samples will be analysed by immunochemistry (IHC)
2 secondary outcomes
western blotting (WB)
Time frame: 1 day
qPolymerase Chain Reaction (PCR)
Time frame: 1 day
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Sep 2016.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jean Louis PUJOL, MD, PhD study director
University Hospital, Montpellier
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Lung Adenocarcinoma, run by University Hospital, Montpellier at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 13 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jean Louis PUJOL, MD, PhD (4 67 33 61 35 ext. 33, jl-pujol@chu-montpellier.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
analysed by immunochemistry (IHC) (time frame: 1 day). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Sep 2016.