The Effects of an Nutritional Intervention on PD-1 ICI in NSCLC

NCT05902260 | Completed DMC

• 1 other identifier: METC2021-0104
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Non-small Cell Lung Cancer

Keywords

immunotherapy; nutritional intervention

Outcome Measures

Primary Outcomes (1)

• 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  Blood for pharmacokinetic analysis and biomarker analysis will be withdrawn in a 5 mL serum tube

  from baseline to end of study (16 weeks)

Secondary Outcomes (2)

• Feasibility of recruiting 50 patients in 1.5 year for this study

  1.5 year after first inclusion

• Feasibility for the subjects to comply with the study protocol

  from baseline to 16 weeks (end of study)

Study Arms (1)

Nutritional intervention

EXPERIMENTAL

Subjects should consume two 200 mL bottles of study product per day

Dietary Supplement: Nutritional intervention; Drug: Immunotherapy

Interventions

Nutritional intervention DIETARY_SUPPLEMENT

Subjects should consume two 200 mL bottles of study product per day next to their cancer treatment (immunotherapy)

Nutritional intervention

Immunotherapy DRUG

Pembrolizumab monotherapy with or without combination chemotherapy according to standard of care

Nutritional intervention

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• Joachim Aerts, MD PhD: lead

Study Sites (1)

Erasmus MC

Rotterdam, 3015 GD, Netherlands

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Immunotherapy

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Immunomodulation; Biological Therapy; Therapeutics

Study Officials

• Joachim Aerts

  Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof dr

Study Record Dates

• First Submitted: March 7, 2023
• First Posted: June 13, 2023
• Study Start: July 6, 2021
• Primary Completion: April 25, 2024
• Study Completion: April 25, 2024
• Last Updated: September 19, 2024

Record last verified: 2024-09

Locations

NL (1)