Evaluating a Fasting-mimicking Diet in Combination With Immunotherapy in Patients With Non-small Cell Lung Cancer (Stage IV NSCLC)

Evaluating the Impact of Intermittent Fasting in Combination With Checkpoint Inhibitors in Patients With Non-small Cell Lung Cancer

The purpose of this study is to learn the effects of fasting on cancer cells while you get maintenance treatment.

Study Overview

• Status: Recruiting
• Conditions: NSCLC; Immunotherapy; Fasting Mimicking Diet; Stage IV NSCLC
• Intervention / Treatment: Combination product: Regular Diet Plus FMD; Dietary supplement: FMD

Detailed Description

Cancer cells use an increased supply of glucose to make energy and do not have protection against fasting that normal cells do. Because of this, researchers would like to study how fasting may help immunotherapy target cancer cells. Initial studies suggest that fasting may decrease the side effects of immunotherapy and increase the chances of your cancer responding to the immunotherapy. Patient populations will have non-small cell lung cancer in which pembrolizumab have been recommended to treat the cancer as part of standard care

• Study Type: Interventional
• Enrollment (Estimated): 66
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Shadia Jalal, MD; Phone Number: (317) 274-5500; Email: Shadia.Jalal@va.gov
• Study Contact Backup: Name: Aleksandra Radovanovich, RN; Phone Number: (317) 988-3338; Email: aleksandra.radovanovich@va.gov

Study Locations

• United States
  • California
    • Long Beach, California, United States, 90822
      • Recruiting
      • VA Long Beach Healthcare System, Long Beach, CA
      • Contact: Pankaj Gupta, MD; Phone Number: 2243 562-826-8000; Email: Pankaj.Gupta@va.gov
      • Contact: Neha Shah, PhD; Phone Number: 13284 5628268000; Email: Neha.shah3@va.gov
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Recruiting
      • Jesse Brown VA Medical Center, Chicago, IL
      • Contact: Larry Feldman, MD; Phone Number: 312-569-5385; Email: lawrence.feldman@va.gov
      • Contact: Cindy Chan; Phone Number: 3129987962; Email: cindy.chan2@va.gov
  • Indiana
    • Indianapolis, Indiana, United States, 46202-2884
      • Recruiting
      • Richard L. Roudebush VA Medical Center, Indianapolis, IN
      • Principal Investigator: Shadia Jalal, MD
      • Contact: Shadia Jalal, MD; Phone Number: (317) 274-5500; Email: Shadia.Jalal@va.gov
      • Contact: Aleksandra Radovanovich, RN; Phone Number: (317) 988-3338; Email: aleksandra.radovanovich@va.gov
  • Missouri
    • St Louis, Missouri, United States, 63106-1621
      • Recruiting
      • St. Louis VA Medical Center John Cochran Division, St. Louis, MO
      • Contact: Theodore Thomas, MD; Phone Number: 53640 314-652-4100; Email: Theodore.Thomas2@va.gov
      • Contact: Carla Prost; Phone Number: 3148143231; Email: Carla.prost@va.gov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 18 years at the time of informed consent
• Ability to provide written informed consent and HIPAA authorization.
• Eastern cooperative group (ECOG) performance status of 0 to 2
• Newly diagnosed histologically or cytologically confirmed stage IV Non-Small Cell Lung Cancer (NSCLC). Patients with locally advanced NSCLC that are not candidates for definitive therapy but are candidates for trial are allowed per investigator discretion.
• BMI 19 kg/m2
• Patients should be enrolled prior to starting standard of care immunotherapy for the treatment of stage IV NSCLC. Patients should be on PD (L)1 inhibitor alone (i.e., with PD-L1 expression 50%) in the metastatic setting. The investigators will allow single agent pembrolizumab only as the checkpoint inhibitor.
• Patients requiring palliative radiation or definitive radiation to an oligometastatic disease prior to the initiation of single agent checkpoint inhibitors are allowed once radiation has been completed and patients have recovered from toxicities.

Exclusion Criteria:

• Self-reported weight loss of > 10% in the 6 weeks prior to study entry
• History of symptomatic hypoglycemia or uncontrolled diabetes
• Prior therapies with inhibitors of insulin growth factor I(IGF-1) such as Linsitinib or Picropodophyllin
• Concurrent use of somatostatin
• Concurrent use of immunosuppressive medications including sirolimus, tacrolimus, mycophenolate mofetil, azathioprine, prednisone, dexamethasone, or cyclosporine
• Significant food allergies which would make the subject unable to consume the food provided.
• History or current evidence of any uncontrolled medical or psychiatric condition, therapy that may confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the participating subject as deemed by the treating investigator.
• Pregnant or lactating females are not eligible.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Regular Diet; Patients will eat a RD with the first 3 cycles, then receive 3 cycles of FMD as they continue cycles 4-6.	Combination product: Regular Diet Plus FMD; Patients will eat a RD with the first 3 cycles, then receive 3 cycles of FMD as they continue cycles 4-6; Other Names: Regular Diet Plus Xentigen
Experimental: FMD; Plant based diet program.	Combination product: Regular Diet Plus FMD; Patients will eat a RD with the first 3 cycles, then receive 3 cycles of FMD as they continue cycles 4-6; Other Names: Regular Diet Plus Xentigen; Dietary supplement: FMD; Plant-based diet program; Other Names: Xentigen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of fasting mimicking diet intervention	Feasibility will be defined as the proportion of the patients who can finish the 3 cycles FMD without serious adverse events. The investigators define FMD as being a feasible intervention in NSCLC receiving checkpoint inhibitors if 70% of patients on study complete 3 cycles of FMD.	Through study completion up to 2 years.
Compliance	Compliance will be measured by analysis of daily food diaries at the end of each FMD cycle.	Through study completion up to 2 years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune Mediated Toxicities	Toxicities as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0.	Through study completion up to 2 years.
Overall response rate (ORR)	ORR defined as complete response (CR) + partial response (PR) per RECIST 1.1 criteria.	Through study completion up to 2 years.
Disease control rate (DCR)	Defined as Complete Response (CR) + Partial Response (PR) + Stable Disease (SD) per RECIST 1.1 .	Through study completion up to 2 years.
Progression Free Survival (PFS)	Defined as time from day 1 of starting on study to disease progression by RECIST 1.1 or death from any cause.	Through study completion up to 2 years.
Functional Assessment of Cancer Therapy-Lung-(FACT-L)	A 36-item, questionnaire measured on a 5-point Likert scale with response options ranging from "not at all" to "very much." Total scores are summed in the range of 0 to 136. Higher scores indicate better QOL.	Through study completion up to 2 years.
European Organization for the Research and Treatment of Cancer Quality of Life -(EORTC QLQ-C30)	A 30-item questionnaire measured on a 4-point response option ranging from ("not at all," to "very much"), except the global QoL scale which, has a 7-point response from ("very poor" to "excellent"). Scores range from 0-100, a higher score represents a higher ("better") level of functioning, or a higher ("worse") level of symptoms.	Through study completion up to 2 years.

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Collaborators: Indiana University; L-Nutra Inc; US Department of Veterans Affairs Cooperative Studies Program
• Investigators: Principal Investigator: Shadia Jalal, MD, Richard L. Roudebush VA Medical Center, Indianapolis, IN

Study record dates

Study Major Dates

• Study Start (Actual): October 27, 2025
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: October 31, 2024
• First Submitted That Met QC Criteria: October 31, 2024
• First Posted (Actual): November 4, 2024

Study Record Updates

• Last Update Posted (Actual): November 10, 2025
• Last Update Submitted That Met QC Criteria: November 5, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: NSCLC; Fasting; PD1 inhibitors; Phase 2; Open Label
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Behavior; Feeding Behavior; Carcinoma, Non-Small-Cell Lung; Fasting; Diet, Food, and Nutrition; Physiological Phenomena; Nutritional Physiological Phenomena; Diet
• Other Study ID Numbers: ONCB-014-24S; 14094145/CX002843 (Other Grant/Funding Number: VA Clinical Science Research & Development)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No