A Nutritional Supplement to Support People With Non-small Cell Lung Cancer

Study Overview
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Brief Summary
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People with non-small cell lung cancer are at risk for nutritional deficiencies. The purpose of this study is to find out what effects a nutritional product has on patient's response to immunotherapy or combination of immunotherapy and chemotherapy. To do this, some of the participants will get the nutritional product and some will receive a placebo (a substance that looks like the study drug but does not have any active or medicinal ingredients). A placebo is used to make the results of the study more reliable. Participants will be randomized to any of the following treatment groups: - Group 1 (Experimental intervention): standard intervention of immunotherapy or combination of immunotherapy and chemotherapy plus the experimental intervention nutritional product. Group 2 (Non-experimental intervention): standard intervention of immunotherapy or combination of immunotherapy and chemotherapy plus the non-experimental intervention placebo product. Participants will take 5 capsules each day by mouth, starting on the first day of immunotherapy with or without chemotherapy and stopping upon completion of their immunotherapy with or without chemotherapy treatment. Participants will complete a diary of their nutritional/ placebo product intake and will undergo the following assessments: Physical examination. Height and weight. ECOG status (the physician will record the impact on the cancer on daily living abilities). Concomitant medications recording. Adverse Event Assessment Computed tomography (CT) scan. A series of x-rays of the body from many angles that are turned into 3-dimensional pictures on a screen. Quality of life questionnaires. Blood collection

Official Title
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Exploring the Effects of a Nutritional Supplement During Immunotherapy or Combination of Immunotherapy and Chemotherapy in Non-small Cell Lung Cancer Patients

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Dietary Supplement: Nutritional supplement
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Subject inclusion criteria Systemic therapy-naïve patients with a histologically confirmed diagnosis of incurable or metastatic stage IIIB/IV non-small cell lung cancer with no EGFR and ALK mutation, who have agreed to receive chemotherapy or both immunotherapy and chemotherapy. Patients who have received prior platinum-based chemotherapy +/- immunotherapy in the curative setting will be allowed to enroll as long as the curative therapy ended at least 12 months prior to enrolment. Age > or = 18 years. A diagnostic CT image taken with a maximum of 60 days before initiation of systemic therapy. An Eastern Cooperative Oncology Group Performance Status of ≤ 2. Patients must have the ability to read, understand, and sign an informed consent and must be willing to comply with study treatment and follow-up. Subject exclusion criteria. Prior other malignancy, active (i.e., requiring treatment or intervention) within the previous 2 years, except for locally curable malignancies that have been apparently cured, which are allowed, such as basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast. Life expectancy <6 months at the discretion of the treating physician Patients currently taking a supplement containing the nutritional supplement under study. Patients should have stopped taking supplements containing the nutritional supplement under study at least 30 days prior to enrolment. A known hypersensitivity / allergy to the investigational product, placebo or to any ingredient in their formulations (e.g. gelatin or glycerin). Enrolment in any other clinical protocol or investigational study with an interventional agent or assessments that may interfere with study procedures. Weight loss >10% over past 6 months (weight 6 months ago minus weight today, divided by weight 6 months ago) x 100 = weight loss%. Blood transfusions within 2 weeks of blood collection for the trial. Untreated brain metastases (patients with previously resected and/or radiated brain metastases without neurologic symptoms are permitted). Subject requires or has received systemic steroid therapy or any other immunosuppressive therapy within 14 days prior to study drug administration. Subjects using a physiologic replacement dose of hydrocortisone or its equivalent (defined as up to 30 mg per day of hydrocortisone, 2 mg per day of dexamethasone or up to 10 mg per day of prednisone) are allowed. Patients may take corticosteroids for ≤4 days as part of routine cancer-directed therapy prophylaxis (e.g., chemotherapy-induced nausea and vomiting). Active autoimmune disease. Subjects with type 1 diabetes mellitus, stable endocrinopathies maintained on appropriate replacement therapy and skin disorders (e.g., vitiligo, psoriasis or alopecia) not requiring systemic treatment are allowed. Uncontrolled diabetes, i.e. with random blood glucose >15.0 mmol/L. Current or expected difficulty or inability to swallow capsules. Use of non-steroidal anti-inflammatory drugs (NSAIDs) for ≥7 consecutive days. Patients are allowed to receive single doses of NSAIDs and may take daily 81 mg ASA. In the investigators' opinion, patients who have medical conditions that could interfere with drug metabolism or absorption (e.g., short bowel syndrome, history of small bowel obstruction, Crohn's disease, etc.) Serum albumin <35 g/L

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental intervention<br>Standard intervention of immunotherapy or combination of immunotherapy and chemotherapy, plus the experimental intervention nutritional product. | Dietary Supplement: Nutritional supplement<br>* Subjects will orally consume two gelatin capsules of nutritional supplement (1 gram), 2 times per day with meals, and 1 capsule at one additional meal or snack, totaling five capsules per day beginning the first day of treatment and continuing for the duration of their treatment.<br>|
| Placebo Comparator: Non-experimental intervention<br>Standard intervention of immunotherapy or combination of immunotherapy and chemotherapy, plus the non-experimental intervention placebo product. | Other: Placebo<br>* Subjects will orally consume two gelatin capsules of placebo (1 gram), 2 times per day with meals, and 1 capsule at one additional meal or snack, totaling five capsules per day beginning the first day of treatment and continuing for the duration of their treatment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease control rate | Disease control rate is defined as the sum of patients with a complete response, partial response or stable disease via RECIST v.1.1 or iRECIST after 4-cycles of immunotherapy or a combination of chemotherapy and immunotherapy. | Upon completion of 4 cycles of treatment (each cycle is 21-days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | Defined as the time from treatment to time of documented disease progression or death. The RECIST v 1.1 or iRECIST will be used as the standardized tumor response assessment on CT images to determine disease progression. | Analysis will occur once 1-year survival data has been collected for all study participants. | 
| 1-year survival | 1-year survival (or death before 1-year) | Analysis will occur once 1-year survival data has been collected for all study participants. | 
| Systemic therapy-induced toxicities | Toxicity will be assessed and graded using the National Cancer Institute CTCAE, version 5.0. | On day 1 of each treatment cycle (each cycle is 21 days) and at the end of treatment visit (within 30 days of last dose) | 
| Change in skeletal muscle mass and adipose tissue | Changes in cross-sectional areas of skeletal muscle will determined using two consecutive CT images from the third lumbar vertebrae region and normalized for stature (cm²/m²). | Upon completion of 4 cycles of chemotherapy (each cycle is 21 days) | 
| Change in Serum CRP | Serum CRP will be determined using enzyme-linked immunosorbent assays. | Upon completion of 4 cycles of chemotherapy (each cycle is 21 days) | 
| Change in Serum Albumin | Serum albumin will be determined using enzyme-linked immunosorbent assays. | Upon completion of 4 cycles of chemotherapy (each cycle is 21 days) | 
| Change in Fatty Acid Incorporation and Omega-3 Index | A phospholipid analysis will be performed on blood samples collected prior to treatment on day 1 of cycles 1-4 and the end of treatment visit. Omega 3-Index will be calculated from the results of the phospholipid analysis. | On day 1 of each treatment cycle (each cycle is 21 days) and at the end of treatment visit (within 30 days of last dose) | 
| Changes in Quality of Life via PROMIS Global Health Scale | The PROMIS Global Health Scale v1.2 will be administered at cycle 1, 3 and at the end of treatment visit. The questionnaire will be scored according to the scoring manual, and changes analyzed to asses the effect of the investigational product on quality of life during treatment. | Questionnaire will be administered at cycle 1 day 1, cycle 3 day 1 (each cycle is 21 days) and at the end of treatment (within 30 days of last dose). | 
| Changes in Quality of Life via PROMIS Physical Function Short Form | The PROMIS Physical Function form v2.0 will be administered at cycle 1, 3 and at the end of treatment visit. The questionnaire will be scored according to the scoring manual, and changes analyzed to asses the effect of the investigational product on quality of life during treatment. | Questionnaire will be administered at cycle 1 day 1, cycle 3 day 1 (each cycle is 21 days) and at the end of treatment (within 30 days of last dose). | 
| Changes in Quality of Life via FAACT | The Functional Assessment of Anorexia Cachexia (FAACT) form version 4 will be administered at cycle 1, 3 and at the end of treatment visit. The questionnaire will be scored according to the scoring manual, and changes analyzed to asses the effect of the investigational product on quality of life during treatment. | Questionnaire will be administered at cycle 1 day 1, cycle 3 day 1 (each cycle is 21 days) and at the end of treatment (within 30 days of last dose). | 
| Changes in Quality of Life via Taste and Smell Survey | The Taste and Smell Survey v29Oct2015 will be administered at cycle 1, 3 and at the end of treatment visit. The questionnaire will be scored according to the scoring manual, and changes analyzed to asses the effect of the investigational product on quality of life during treatment. | Questionnaire will be administered at cycle 1 day 1, cycle 3 day 1 (each cycle is 21 days) and at the end of treatment (within 30 days of last dose). | 
| Disease Control Rate after 2 cycles | Disease control rate is defined as the sum of patients with a complete response, partial response or stable disease after 2 cycles of systemic therapy divided by the number of patients in the group. The Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or iRECIST will be used as the standardized tumor response assessment on CT images. | Upon completion of 2 cycles of treatment (each cycle is 21-days) |