Non-small Cell Lung CancerNutriCimNCT05902260
The Effects of an Nutritional Intervention on PD-1 ICI in NSCLC
A study testing Nutritional intervention and Immunotherapy in people with Non-small Cell Lung Cancer, run by Joachim Aerts, MD PhD at 1 site in Netherlands.
Trial summary
Over 65% of all lung cancer patients experience significant weight loss fuelled by a catabolic state that is represented by enhanced protein breakdown. The metabolic state of patients is a key effector of protein clearance, and the increased albumin as well as monoclonal antibodies clearance that is observed in… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-small Cell Lung Cancer
- What is being tested?
- Nutritional intervention and Immunotherapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 51 participants
- Where
- 1 siteNetherlands
- Study dates
- 6 Jul 2021to 25 Apr 2024
- Phase
- Interventional
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- Subjects must have programmed death-ligand 1 (PD -L1) immunohistochemical (IHC) testing.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
- Measurable disease by CT per response evaluation criteria in solid tumors version 1.1 (RECIST 1.1) criteria
- Adequate haematological, renal and liver function
Who cannot join
- 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 ≥14.0 mg/dL (3.5 mmol/L)
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effects of an Oncology Tailored Nutritional Intervention on the Bioavailability and Immune-activity of PD-1 Immune Checkpoint Inhibitors in Patients with Lung Cancer
Over 65% of all lung cancer patients experience significant weight loss fuelled by a catabolic state that is represented by enhanced protein breakdown. The metabolic state of patients is a key effector of protein clearance, and the increased albumin as well as monoclonal antibodies clearance that is observed in patients with progressive cancer disease inversely correlates with treatment response and may well be consequential to changes in the metabolic state of cancer patients. Interestingly, several studies in cancer patients receiving chemotherapy, amongst which are NSCLC patients, have shown that weight loss and catabolism can be prevented or improved by intake of high energy/high protein Oral Nutritional Supplements (ONS). 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.
The investigators hypothesize that high energy/high protein nutritional supplements decrease protein clearance including drug clearance in NSCLC patients receiving 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.
The primary aim is to investigate the variability of clearance during a 12-weeks nutritional intervention period. The secondary aim is to investigate the feasibility for the subjects to comply with the study protocol. Lastly, the investigators aim to study the feasibility of gathering data on a number of exploratory parameters that may link nutritional intake to clinically relevant outcomes.
Read the detailed description
Rationale: Over 65% of all lung cancer patients experience significant weight loss fuelled by a catabolic state that is represented by enhanced protein breakdown. The metabolic state of patients is a key effector of protein clearance, and the increased albumin as well as monoclonal antibodies clearance that is observed in patients with progressive cancer disease inversely correlates with treatment response and may well be consequential to changes in the metabolic state of cancer patients. Interestingly, several studies in cancer patients receiving chemotherapy, amongst which are NSCLC patients, have shown that weight loss and catabolism can be prevented or improved by intake of high energy/high protein Oral Nutritional Supplements (ONS).
The investigators hypothesize that high energy/high protein nutritional supplements decrease protein clearance including drug clearance in NSCLC patients receiving 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, nutritional 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.
Objective: The primary aim is to investigate the variability of clearance during a 12-weeks nutritional intervention period. The secondary aim is to investigate the feasibility for the subjects to comply with the study protocol. Lastly, the investigators aim to study the feasibility of gathering data on a number of exploratory parameters that may link nutritional intake to clinically relevant outcomes.
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 microbiome status with a primary focus on pembrolizumab clearance.
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.
- Conditions
- Non-small Cell Lung Cancer
- Being tested
- Nutritional intervention, Immunotherapy
- Keywords
- immunotherapy, nutritional intervention
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nutritional interventionDietary supplement
Subjects should consume two 200 mL bottles of study product per day next to their cancer treatment (immunotherapy)
ImmunotherapyDrug
Pembrolizumab monotherapy with or without combination chemotherapy according to standard of care
| Study group | Role | What they receive |
|---|---|---|
| Nutritional intervention | Experimental | Subjects should consume two 200 mL bottles of study product per day Receives: Dietary Supplement: Nutritional intervention; Drug: Immunotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
The variability of clearance of pembrolizumab during a 12-weeks nutritional intervention period in NSCLC patients receiving anti PDL-1 treatment,
Blood for pharmacokinetic analysis and biomarker analysis will be withdrawn in a 5 mL serum tube
Measured: from baseline to end of study (16 weeks)
Secondary outcomes (2)
Feasibility of recruiting 50 patients in 1.5 year for this study
Recruitment rate of patient inclusion, every patient eligible for this study will be asked for enrollment
Measured: 1.5 year after first inclusion
Feasibility for the subjects to comply with the study protocol
Rate of compliance to the study procedures including the intake of the nutritional intervention and the feasibility of data collection.
Measured: from baseline to 16 weeks (end of study)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2023
- Study start6 Jul 2021
- Primary completion25 Apr 2024
- Study completion25 Apr 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-small Cell Lung CancerStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- Joachim Aerts, MD PhD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Joachim Aerts, MD PhD, Erasmus Medical Center
- Investigators
- Joachim Aerts, Principal investigator, Erasmus Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05902260
- Sponsor's protocol ID
- METC2021-0104
- Acronym
- NutriCim
- Status last verified
- Sep 2024
- First submitted
- 7 Mar 2023
- Last updated
- 19 Sep 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of an Oncology Tailored Nutritional Intervention on the Bioavailability and Immune-activity of PD-1 Immune Checkpoint Inhibitors in Patients with Lung Cancer
- ClinicalTrials.gov ID
- NCT05902260
- Acronym / sponsor ID
- NutriCim / METC2021-0104
- Conditions
- Non-small Cell Lung Cancer
- Keywords
- immunotherapy, nutritional intervention
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 51 participants (actual)
- Lead sponsor
- Joachim Aerts, MD PhDUniversity, hospital or other
- Study start
- 6 Jul 2021 (actual)
- Primary completion
- 25 Apr 2024 (actual)
- Study completion
- 25 Apr 2024 (actual)
- First posted
- 13 Jun 2023 (actual)
- 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.
Over 65% of all lung cancer patients experience significant weight loss fuelled by a catabolic state that is represented by enhanced protein breakdown. The metabolic state of patients is a key effector of protein clearance, and the increased albumin as well as monoclonal antibodies clearance that is observed in patients with progressive cancer disease inversely correlates with treatment response and may well be consequential to changes in the metabolic state of cancer patients. Interestingly, several studies in cancer patients receiving chemotherapy, amongst which are NSCLC patients, have shown that weight loss and catabolism can be prevented or improved by intake of high energy/high protein Oral Nutritional Supplements (ONS). 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.
The investigators hypothesize that high energy/high protein nutritional supplements decrease protein clearance including drug clearance in NSCLC patients receiving 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.
The primary aim is to investigate the variability of clearance during a 12-weeks nutritional intervention period. The secondary aim is to investigate the feasibility for the subjects to comply with the study protocol. Lastly, the investigators aim to study the feasibility of gathering data on a number of exploratory parameters that may link nutritional intake to clinically relevant outcomes.
Detailed description
Rationale: Over 65% of all lung cancer patients experience significant weight loss fuelled by a catabolic state that is represented by enhanced protein breakdown. The metabolic state of patients is a key effector of protein clearance, and the increased albumin as well as monoclonal antibodies clearance that is observed in patients with progressive cancer disease inversely correlates with treatment response and may well be consequential to changes in the metabolic state of cancer patients. Interestingly, several studies in cancer patients receiving chemotherapy, amongst which are NSCLC patients, have shown that weight loss and catabolism can be prevented or improved by intake of high energy/high protein Oral Nutritional Supplements (ONS).
The investigators hypothesize that high energy/high protein nutritional supplements decrease protein clearance including drug clearance in NSCLC patients receiving 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, nutritional 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.
Objective: The primary aim is to investigate the variability of clearance during a 12-weeks nutritional intervention period. The secondary aim is to investigate the feasibility for the subjects to comply with the study protocol. Lastly, the investigators aim to study the feasibility of gathering data on a number of exploratory parameters that may link nutritional intake to clinically relevant outcomes.
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 microbiome status with a primary focus on pembrolizumab clearance.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Nutritional intervention | Experimental | Dietary Supplement: Nutritional intervention, Drug: ImmunotherapySubjects should consume two 200 mL bottles of study product per day |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
- Subjects must have programmed death-ligand 1 (PD -L1) immunohistochemical (IHC) testing.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
- Measurable disease by CT per response evaluation criteria in solid tumors version 1.1 (RECIST 1.1) criteria
Key exclusion criteria (9 listed)
- 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
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 |
|---|---|---|
| Nutritional interventionSubjects should consume two 200 mL bottles of study product per day next to their cancer treatment (immunotherapy) | Dietary supplement | Nutritional intervention |
| ImmunotherapyPembrolizumab monotherapy with or without combination chemotherapy according to standard of care | Drug | Nutritional intervention |
Primary outcome
The variability of clearance of pembrolizumab during a 12-weeks nutritional intervention period in NSCLC patients receiving anti PDL-1 treatment,
Time frame: from baseline to end of study (16 weeks)
Blood for pharmacokinetic analysis and biomarker analysis will be withdrawn in a 5 mL serum tube
2 secondary outcomes
Feasibility of recruiting 50 patients in 1.5 year for this study
Time frame: 1.5 year after first inclusion
Feasibility for the subjects to comply with the study protocol
Time frame: from baseline to 16 weeks (end of study)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- 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.
Joachim Aerts principal investigator
Erasmus Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Nutritional intervention and Immunotherapy in people with Non-small Cell Lung Cancer, run by Joachim Aerts, MD PhD at 1 site in Netherlands.
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 6 inclusion and 9 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: finished, as of the sponsor's last update on 19 Sep 2024. 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 Netherlands. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The variability of clearance of pembrolizumab during a 12-weeks nutritional intervention period in NSCLC patients receiving anti PDL-1 treatment, (time frame: from baseline to end of study (16 weeks)). 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 19 Sep 2024.