Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04487457 |
| Other study ID # |
RIPH3-RNI20 / CINECI |
| Secondary ID |
2020-A01478-31 |
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
September 3, 2021 |
| Est. completion date |
September 29, 2022 |
Study information
| Verified date |
April 2023 |
| Source |
University Hospital, Tours |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Non-small cell lung cancer (NSCLC) is the most common histological form, accounting for 85%
of all bronchopulmonary cancers (PBC). The advent of Immunity Checkpoint Inhibitors (ICIs)
targeting Programmed cell Death-1 (PD-1) is changing current treatment algorithms.
Preliminary results from work carried out in the Medical Oncology Department of the
University Hospital of Tours suggest that immunotherapy targeting ICI, when administered
beforehand, increases the effect of catch-up chemotherapy. In NSCLC, the progression-free
survival (PFS) of 3rd line chemotherapy after anti-PD-1 immunotherapy was better than the PFS
of 3rd line chemotherapy performed at the end of conventional chemotherapy. Moreover, the
combination of chemotherapy and immunotherapy gives paradoxically better results than
immunotherapy alone.
Immunotherapy restores the anti-tumor T immunity inhibited by the cancer cell. While the mode
of action of ICIs is well known, the mechanisms of resistance to them are poorly understood.
Several pathways are evoked, in particular the modulation of cellular interactions within the
tumour microenvironment (TME), the molecular expression profile of cancer cells, or the
immunological status of the patient.
Regulatory T lymphocytes (Treg) participate in the maintenance of immune system homeostasis
by ensuring tolerance to self antigens. Within TME, Treg inhibit anti-tumor T cell activity
and potentiate tumor proliferation. The latter, by specifically recognizing tumor antigens,
block the activity of effector T lymphocytes directed against tumor cells. Thus, an increase
in circulating Treg concentrations and in TME is a poor prognostic factor, especially in
NSCLC.
Gemcitabine chemotherapy is commonly used in the management of NSCLC. Recent data show that
gemcitabine decreases Treg activity and regulates levels of anti-inflammatory TME cytokines
such as IL10, TGF-β and interferon-Ɣ.
The hypothesis of this study is that the decrease in Treg blood concentration by catch-up
chemotherapy restores sensitivity to immunotherapy.
Description:
Non-small cell lung cancer (NSCLC) is the most common histological form, accounting for 85%
of all bronchopulmonary cancers (PBC). The advent of Immunity Checkpoint Inhibitors (ICIs)
targeting Programmed cell Death-1 (PD-1) is changing current treatment algorithms.
Preliminary results from work carried out in the Medical Oncology Department of the
University Hospital of Tours suggest that immunotherapy targeting ICI, when administered
beforehand, increases the effect of catch-up chemotherapy. In NSCLC, the the progression-free
survival (PFS) of 3rd line chemotherapy after anti-PD-1 immunotherapy was better than the PFS
of 3rd line chemotherapy performed at the end of conventional chemotherapy. Moreover, the
combination of chemotherapy and immunotherapy gives paradoxically better results than
immunotherapy alone.
Immunotherapy restores the anti-tumor T immunity inhibited by the cancer cell. While the mode
of action of ICIs is well known, the mechanisms of resistance to them are poorly understood.
Several pathways are evoked, in particular the modulation of cellular interactions within the
tumour microenvironment (TME), the molecular expression profile of cancer cells, or the
immunological status of the patient.
Regulatory T lymphocytes (Treg) participate in the maintenance of immune system homeostasis
by ensuring tolerance to self antigens. Within TME, Treg inhibit anti-tumor T cell activity
and potentiate tumor proliferation. The latter, by specifically recognizing tumor antigens,
block the activity of effector T lymphocytes directed against tumor cells. Thus, an increase
in circulating Treg concentrations and in TME is a poor prognostic factor, especially in
NSCLC.
Gemcitabine chemotherapy is commonly used in the management of NSCLC. Recent data show that
gemcitabine decreases Treg activity and regulates levels of anti-inflammatory TME cytokines
such as IL10, TGF-β and interferon-Ɣ.
The hypothesis of this study is that the decrease in Treg blood concentration by catch-up
chemotherapy restores sensitivity to immunotherapy.
