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

(Stage IV NSCLC Trial)

Recruiting at 3 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

Trial Summary

What is the purpose of this trial?

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

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 data supports the effectiveness of the treatment FMD for non-small cell lung cancer?

Research shows that a fasting-mimicking diet (FMD) can enhance the effectiveness of cancer treatments by improving the body's immune response and reducing side effects. In studies with mice and some cancer patients, FMD helped boost the effects of standard cancer therapies, suggesting it might also be beneficial for non-small cell lung cancer when combined with immunotherapy. ^{1 2 3 4 5}

Is the fasting-mimicking diet safe for humans?

The fasting-mimicking diet (FMD) has been shown to be safe in clinical trials involving 101 patients with cancer, where it was combined with standard cancer treatments. It resulted in significant metabolic changes and was well tolerated, suggesting it is generally safe for human use. ^{1 2 4 5 6}

How does the fasting-mimicking diet treatment differ from other treatments for non-small cell lung cancer?

The fasting-mimicking diet (FMD) is unique because it involves cycles of a low-calorie, low-carbohydrate, and low-protein diet that mimics fasting, which can enhance the effectiveness of standard cancer treatments like immunotherapy. This approach not only helps in reducing blood sugar and growth factors that fuel cancer but also boosts the body's immune response against tumors, potentially leading to better outcomes with fewer side effects compared to traditional treatments alone. ^{1 2 3 6 7}

Research Team

Shadia Jalal, MD

Principal Investigator

Richard L. Roudebush VA Medical Center, Indianapolis, IN

Eligibility Criteria

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

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

Ability to provide written informed consent and HIPAA authorization

BMI 19 kg/m2

Exclusion Criteria

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.

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

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Exceptional tumour responses to fasting-mimicking diet combined with standard anticancer therapies: A sub-analysis of the NCT03340935 trial. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Fasting-Mimicking Diet Is Safe and Reshapes Metabolism and Antitumor Immunity in Patients with Cancer. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Fasting renders immunotherapy effective against low-immunogenic breast cancer while reducing side effects. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Fasting-mimicking diet synergizes with ferroptosis against quiescent, chemotherapy-resistant cells. [2023]

5. Netherlands 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. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Fasting potentiates the anticancer activity of tyrosine kinase inhibitors by strengthening MAPK signaling inhibition. [2018]

7. England 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. [2021]