The predictive value of the microbiome (throat swabs and stool samples) to identify patients who will relapse during durvalumab treatment after CRT (False negative Rate) at 6 months. Exploratory endpoints include the effects of antibiotic therapy…
ID
Source
Brief title
Condition
- Respiratory and mediastinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Progression of disease defined by regular CT scan and physical examination and
occurrence of toxicity.
Secondary outcome
Changes in circulating immune cells.
Background summary
Despite the improvements in Overall and Progression Free Survival in patients
treated with concurrent or sequential chemoradiotherapy followed by
consolidation therapy with PD-1 blockade (durvalumab), a significant number of
patients suffer from recurrent disease within one year.
To allow for a more adequate patient follow-up, identification of a biomarker
predicting early recurrence or long-lasting disease control is required. The
former group could be monitored more closely while the latter can suffice with
less outpatient visits and less radiological evaluations. Ineffective therapies
can be ceased earlier and allow a switch to a more effective regimen. This
seems appropriate since assessment of tumor recurrence after ChemoRT is more
complicated due to the ample possibility of non-malignant changes in the lung
(radiation pneumonitis or infection). So far, no biomarkers have been
identified for this purpose.
Recently, the microbiome has attracted attention for its ability to modify the
immune system and thereby changing the immune surveillance in humans. This is
considered to be of pivotal importance to sustain a long-lasting tumor control
in different tumor types treated with immune checkpoint inhibitors.
Study objective
The predictive value of the microbiome (throat swabs and stool samples) to
identify patients who will relapse during durvalumab treatment after CRT (False
negative Rate) at 6 months. Exploratory endpoints include the effects of
antibiotic therapy before and during IO treatment on toxicity and response
rate.
Mass cytometry (CyTOF) of circulating immune cells will be examined in a subset
of patients including metabolome analysis.
Study design
This is a prospective observational multicenter study, during 2 years, 126
patients will be included after first inclusion. Patients be included from 2
centers in the Netherlands and 4 centers in Belgium.
Study burden and risks
Collection of stool and throat swipe before start of durvalumab treatment;
sampling of blood for analysis of volatile organic compounds. No benefit is
foreseen in participation to this study.
Albinusdreef 2
Leiden 2333ZA
NL
Albinusdreef 2
Leiden 2333ZA
NL
Listed location countries
Age
Inclusion criteria
1. Stages IIIA, IIIB and IIIC (as per UICC 8th TNM edition) NSCLC
(histologically or cytologically confirmed) amenable for concurrent
chemoradiotherapy according to multidisciplinary tumor board.
2. No signs of disease progression after Chemoradiation (sequential and
concurrent)
3. At least 1 cycle of chemotherapy as part of the radiotherapy schedule but no
more chemotherapy between last radiotherapy session and start durvalumab
4. Absence of any of following targetable driver mutations: (EGFR, ALK, ROS1)
5. >= 18 years
6. ECOG <= 1
7. Must be willing to provide collected stool samples and allow to obtain a
throat swab during the observation period.
8. Demonstrate adequate organ function, all screening labs should be performed
within 10 days of start durvalumab
Exclusion criteria
1. Is currently participating in or has participated in a study of an
investigational agent or using an investigational device within 4 weeks of the
first dose of treatment.
2. Has had prior monoclonal antibody therapy within 4 weeks prior to study Day
1 or who has not recovered (i.e., <= Grade 1 or at baseline) from adverse events
due to agents administered more than 4 weeks earlier.
3. Previous treatment with PD-1-PD-L1 axis inhibiting immunotherapy.
4. Active or history of autoimmune disease or immune deficiency,
5. Subjects with a condition requiring systemic treatment with either
corticosteroids (> 10 mg daily prednisone equivalents) or other
immunosuppressive medications within 14 days of study drug administration
6. Has evidence of symptomatic interstitial lung disease or an active,
non-infectious pneumonitis.
Design
Recruitment
Medical products/devices used
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT04711330 |
| CCMO | NL76017.058.21 |