Fasting-Mimicking Diet and Immunotherapy for Non-Small Cell Lung Cancer

(Stage IV NSCLC Trial)

Recruiting at 5 trial locations

Overseen By Shadia Jalal, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: VA Office of Research and Development

Must be taking: PD-L1 inhibitors

Must not be taking: Immunosuppressants, IGF-1 inhibitors

Disqualifiers: Uncontrolled diabetes, Significant food allergies, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years

66 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how a fasting-mimicking diet (a special plant-based diet) might affect cancer cells in individuals with non-small cell lung cancer (NSCLC) undergoing maintenance treatment. Researchers aim to determine if this diet can enhance the effects of immunotherapy. The trial includes two groups: one will follow the fasting-mimicking diet, while the other will begin with a regular diet before switching to the fasting-mimicking diet. This trial suits individuals with stage IV NSCLC who are about to start immunotherapy and do not have significant weight loss or diabetes issues. As an unphased trial, it provides an opportunity to explore innovative dietary approaches that could improve cancer treatment outcomes.

Will I have to stop taking my current medications?

The trial requires that you do not take certain medications, such as immunosuppressive drugs like prednisone or dexamethasone, while participating. If you are on these medications, you may need to stop them to join the trial.

What prior data suggests that this fasting-mimicking diet is safe for non-small cell lung cancer patients?

Research has shown that the fasting-mimicking diet (FMD) is generally safe for most people. Several studies have found that individuals can follow FMD without major issues, experiencing only mild side effects. For instance, one study noted that participants maintained their weight and muscle strength while on this diet. Another study found that FMD is safe and can improve how the body processes food. These results suggest that FMD is a safe choice for many people, including those receiving cancer treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using a Fasting-Mimicking Diet (FMD) for non-small cell lung cancer because it offers a unique approach compared to traditional treatments like chemotherapy and immunotherapy. Unlike these standard treatments, which target cancer cells directly, the FMD is a plant-based diet program designed to simulate the effects of fasting, potentially enhancing the body's natural immune response against cancer. This approach may improve the effectiveness of existing immunotherapies by creating a more favorable environment for the immune system to attack cancer cells. The idea is to boost the body's defenses while maintaining nutrition, which represents a novel strategy in cancer treatment.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

Research shows that a fasting-mimicking diet (FMD) might help treat cancer. In this trial, participants will initially follow either an FMD or a regular diet, with some transitioning to FMD in later cycles. Studies suggest that FMD can enhance the effectiveness of chemo-immunotherapy for individuals with non-small cell lung cancer (NSCLC). In certain cancer studies, FMD has slowed tumor growth when combined with immunotherapy. Additionally, short-term fasting like FMD may reduce chemotherapy side effects and improve the likelihood of a positive cancer response. Early findings indicate that FMD is safe for cancer patients and could positively impact their health. ^{2 4 6 7 8}

Who Is on the Research Team?

Shadia Jalal, MD

Principal Investigator

Richard L. Roudebush VA Medical Center, Indianapolis, IN

Are You a Good Fit for This Trial?

This trial is for individuals with Non-Small Cell Lung Cancer who are currently receiving maintenance immunotherapy. The study aims to understand how a special diet that mimics fasting affects cancer treatment.

Inclusion Criteria

Ability to provide written informed consent and HIPAA authorization

BMI 19 kg/m2

I have been newly diagnosed with stage IV NSCLC or have advanced NSCLC not eligible for standard treatment but can join a trial.

Exclusion Criteria

Significant food allergies which would make the subject unable to consume the food provided

I have lost more than 10% of my weight in the last 6 weeks.

I have been treated with drugs targeting IGF-1 like Linsitinib.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a fasting-mimicking diet in combination with immunotherapy for non-small cell lung cancer

Up to 2 years

Regular visits as per treatment cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• FMD

Trial Overview Participants will either continue their regular diet or switch to a Fasting Mimicking Diet (FMD) while undergoing their standard immunotherapy treatments. The goal is to see if the FMD can improve the effectiveness of the therapy.

How Is the Trial Designed?

Group I: FMD Experimental Treatment 2 Interventions

Plant based diet program.

Group II: Regular Diet Active Control 1 Intervention

Patients will eat a RD with the first 3 cycles, then receive 3 cycles of FMD as they continue cycles 4-6.

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Indiana University

Collaborator

Trials

1,063

Recruited

1,182,000+

US Department of Veterans Affairs Cooperative Studies Program

Collaborator

Trials

3

Recruited

710+

L-Nutra Inc

Industry Sponsor

Trials

10

Recruited

730+

Published Research Related to This Trial

In a study of 131 patients with HER2-negative stage II/III breast cancer, a fasting mimicking diet (FMD) during chemotherapy did not increase toxicity compared to a regular diet, even without the use of dexamethasone.

Patients on the FMD showed significantly better treatment responses, with a higher likelihood of achieving complete or partial tumor response and a greater chance of 90-100% tumor-cell loss, indicating enhanced therapeutic efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fasting mimicking diet as an adjunct to neoadjuvant chemotherapy for breast cancer in the multicentre randomized phase 2 DIRECT trial. de Groot, S., Lugtenberg, RT., Cohen, D., et al.[2021]

In a phase Ib trial involving 101 patients with advanced cancer, cyclic fasting-mimicking diets (FMDs) were found to be safe and feasible when combined with standard cancer treatments, showing positive metabolic and immunologic changes.

Remarkably, five patients with poor prognosis solid tumors achieved complete and long-lasting tumor remissions, suggesting that cyclic FMD may enhance the effectiveness of standard anticancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exceptional tumour responses to fasting-mimicking diet combined with standard anticancer therapies: A sub-analysis of the NCT03340935 trial. Ligorio, F., Fucà, G., Provenzano, L., et al.[2022]

Fasting or a fasting-mimicking diet (FMD) can slow down tumor growth but does not enhance the sensitivity of colorectal cancer (CRC) cells to chemotherapy drugs like 5-fluorouracil and oxaliplatin, indicating a complex relationship between fasting and cancer treatment.

The study identified that fasting induces CRC cells to enter a slow-cycling state, which may lead to the development of drug-tolerant persister cells that contribute to cancer relapse; however, combining fasting with ferroptosis inducers could enhance tumor inhibition and target these resistant cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fasting-mimicking diet synergizes with ferroptosis against quiescent, chemotherapy-resistant cells. Liu, X., Peng, S., Tang, G., et al.[2023]

In a phase II study involving 129 patients with HER2-negative breast cancer, a fasting mimicking diet (FMD) improved patients' perceptions of chemotherapy side effects and overall quality of life compared to a regular diet.

Patients adhering to the FMD reported better emotional, physical, and social functioning, along with lower levels of fatigue, nausea, and insomnia, suggesting that FMD may enhance the supportive care during neoadjuvant chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality of life and illness perceptions in patients with breast cancer using a fasting mimicking diet as an adjunct to neoadjuvant chemotherapy in the phase 2 DIRECT (BOOG 2013-14) trial. Lugtenberg, RT., de Groot, S., Kaptein, AA., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10037739/

Short-term fasting and fasting mimicking diets combined ... In this narrative review, we identify and describe the current evidence about feasibility and effects of STF and FMDs in cancer patients receiving chemotherapy.

2. sciencedirect.com sciencedirect.com/science/article/pii/S1550413124002705

Cyclic fasting-mimicking diet in cancer treatment In non-small cell lung cancer (NSCLC) models that are primarily resistant to ICIs, fasting or immunotherapy alone do not affect tumor growth ...

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2019-00699

Fasting-mimicking Diet in Increasing the Effectiveness of ... This pilot phase II trial studies how well a fasting-mimicking diet works in increasing the effectiveness of chemo-immunotherapy in patients with non-small ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03700437

Study Details | NCT03700437 | Fasting-mimicking Diet ... Initial studies suggest that fasting may decrease the side effects of chemotherapy and increase the chances of your cancer responding to the chemotherapy.

5. aacr.org aacr.org/patients-caregivers/progress-against-cancer/fasting-mimicking-diet-found-safe-and-potentially-helpful-to-cancer-patients/

“Fasting-mimicking” Diet Found Safe and Potentially ... A diet involving short-term, severe calorie restriction was safe and resulted in biological effects in the body that may be helpful in cancer treatment.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8391327/

Safety and Feasibility of Fasting-Mimicking Diet and Effects ... FMD was largely safe with only mild side effects. The patients' weight and handgrip remained stable, the phase angle and fat-free mass increased ...

7. annalsofoncology.org annalsofoncology.org/article/S0923-7534(20)34965-6/fulltext

Safety and metabolic effects of the fasting mimicking diet in ... Our interim analysis suggests that the proposed FMD scheme is safe and significantly modifies systemic metabolism in a heterogeneous population of cancer pts.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06671613

Evaluating a Fasting-mimicking Diet in Combination With ... Study Overview. The purpose of this study is to learn the effects of fasting on cancer cells while you get maintenance treatment.