The aim is to investigate whether it is feasible to perform a 12-weeks nutritional intervention study in NSCLC patients on PD-1 ICI, and to effectively assess their nutritional, immune, and microbial status, with the intention to use this…
ID
Source
Brief title
Condition
- Respiratory and mediastinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main endpoint is the recruitment rate: how many patients can be recruited
in 1 year? Secundary endpoints are the rate of compliance to the study
procedures including the intake of the nutritional intervention and the rate of
data collection (blood samples, fecal samples, diaries). In order to study
feasibility of an nutritional intervention study in NSCLC patients receiving
anti PDL-1 treatment, the primary objective is to assess whether it is possible
to recruit 50 patients in 1.5 year for this study. The secondary objective is
to assess whether it is feasible for the subjects to comply with the study
protocol (i.e. undergo study assessments and collect blood and faecal samples
at the indicated time points). Lastly, exploratory objectives are to study the
effect of the nutritional intervention on anti-PD-1 drug clearance, immune
activation status, nutritional status, microbiome status, and clinical
response.
Secondary outcome
not applicable
Background summary
Several studies in cancer patients receiving chemotherapy have shown that
nutritional supplements influences catabolism. We hypothesize that high
energy/high protein nutritional supplements decrease protein clearance
including drug clearance in NSCLC patients reveiving anti-PD-1 ICIs, which on
its turn would positively affect anti-PD-1 drug bioavailability, leading to
activation of the immune system and thereby an increased response to PD-1 ICIs.
An increased clearance of anti-PD-1 ICI may also represent a general
dysfunctioning of the immune system, because immune cell activation,
proliferation, migration and tumor cell killing may all be influenced by
cachexia. Enrichment of nutritional supplements with specific nutrients known
to have immune-modulating properties, may further balance immune responses
supportive of ICI efficacy.
In conclusion, nutrional intervention with high energy/high protein nutritional
supplements, especially if enriched with nutrients known for their immune- or
microbiome-modulation properties, may have a positive impact on several
mechanisms underlying cachexia-induced PD-1 ICI efficacy impairment. Lung
cancer (NSCLC) patients are a relevant target population to investigate the
clinical relevance of a nutritional intervention on anti-PD-1 ICI, because
NSCLC is one of the cancer types with highest prevalence of cancer-induced
cachexia amongst patients and PD-1 ICI is a standard of care treatment for
these patients. However, nutritional intervention studies in a vulnerable
patient population, such as patients with cancer, can be perceived as a burden,
especially when there are a lot of additional assessments (e.g. questionnaires,
diaries, blood sampling, fecal sampling). Therefore, the recruitment of
sufficient representative patients within a certain time period can be
challenging.
Study objective
The aim is to investigate whether it is feasible to perform a 12-weeks
nutritional intervention study in NSCLC patients on PD-1 ICI, and to
effectively assess their nutritional, immune, and microbial status, with the
intention to use this information for designing an efficacy study to
effectively show the added value of a nutritional intervention in cancer
patients undergoing immunotherapy.
Study design
NutriCim is a feasibility study specifically designed to gather information on:
(i) the rate of NSCLC patient recruitment,(ii) the feasibility of collecting
relevant data (compliance to protocol), and (iii) the effects of nutritional
intervention on a number of parameters representing the patients* nutritional,
immune, and microbiomal status.
Patients will start with the daily nutritional intervention prior to start of
the first infusion of anti-PD-1 ICI immunotherapy and will continue this
nutritional support for 4 treatment cycles, corresponding with 12 weeks of
treatment. Blood samples, questionnaires and faecal specimens will be
collected on several time points during this treatment. Changes from baseline
for the different parameters on an individual patient level will, taking into
account nutritional supplements compliance, be compared to patient outcomes, as
well as with a historical cohort of NSCLC patients on similar treatment not
receiving nutritional supplements.
Intervention
Patients will start with 2 times daily nutritional intervention preferably 5
days (with a minum of 3 days) prior to start the first infusion of
immunotherapy, and remain on treatment and nutritional intervention for the
period of 4 cycles of q3week treatment.
Study burden and risks
In the studyprocedures the only intervention is the drawal of blood sampes,
which is accompanied by a negligible addition risk of complications.
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Listed location countries
Age
Inclusion criteria
Participants are eligible to be included in the study if the following criteria
apply:
• Age > 18 years
• Patient must be willing and capable of giving written Informed Consent, and
meeting all study requirements
• Capable of oral intake and digestion of the nutritional test product
• Subjects with cytologically confirmed Stage IV or recurrent NSCLC, who have
not received prior systemic therapy treatment for their advanced NSCLC.
Completion of treatment with cytotoxic chemotherapy, biological therapy, and/or
radiation as part of neoadjuvant/adjuvant therapy is allowed as long as therapy
was completed at least 6 months prior to the diagnosis of metastatic disease.
Exclusion criteria
• Subject with an active auto-immune disease requiring systemic treatment
• Lung disease requiring systemic steroids in doses of >10 mg prednisolone (or
equivalent dose of other steroid)
• Previous allogeneic or organ transplant
• Serious concomitant systemic disorders (for example active infection,
unstable cardiovascular disease) which in the opinion of the investigator would
compromise the patient's ability to complete the study, or would interfere with
the evaluation of the efficacy and safety of the study treatment
• Known positive test for hepatitis B virus or hepatitis C virus or human
immunodeficiency virus (HIV) indicating acute or chronic infection
• Allergy to cow*s milk protein, soy or fish, requiring a fibre-free diet or
suffering galactosemia or lactose intolerance
• Moderate to severe hypercalcemia, i.e. total calcium level corrected for
albumin >=142.0 mg/dL (3.05 mmol/L )
• Patient has had other malignancies within the past 3 years , except for
stable non-melanoma skin cancer, fully treated and stable early stage prostate
cancer or carcinoma in situ of the cervix or breast without need of treatment
• Simultaneous participation in other clinical trial
• Pregnant or lactating women
Design
Recruitment
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 |
|---|---|
| CCMO | NL76015.078.21 |