A Pilot Study Evaluating a Ketogenic Diet Concomitant to Nivolumab and Ipilimumab in Patients With Metastatic Renal Cell Carcinoma

NCT05119010 | Terminated

• 2 other identifiers: 2020-A03550-392020/3206
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to assess objective response rate (partial and complete response) of Nivolumab and Ipilimumab concomitant to a special diet (ketogenic diet, continuous or discontinuous) or standard diet with or without BHB according to RECIST v1.1 at 8 weeks.

Conditions

Metastatic Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Objective response rate

  Preliminary activity will be assessed by measuring objective response rate (ORR) (partial/complete response) of Nivolumab plus Ipilimumab concomitant to a special diet (KD continuous or discontinuous) or standard diet (SD) with or without (BHB) according to RECIST v1.1 at 8 weeks.

  at 8 weeks after diet initiation.

Secondary Outcomes (10)

• Safety of Nivolumab plus Ipilimumab concomitant to a special diet

  Events reported from the first day of diet and up to and including 100 days following the last day of diet could be included in estimating this incidence rate.

• Assessment of weight

  from the first day of diet and up to 2 years from diet initiation

• Assessment of albuminemia

  from the first day of diet and up to 2 years from diet initiation

• Assessment of prealbuminemia

  from the first day of diet and up to 2 years from diet initiation

• Assessment of C reactive protein

  from the first day of diet and up to 2 years from diet initiation

Study Arms (4)

A

EXPERIMENTAL

patients will be asked to follow in a continuous way a very low-carbohydrate, high-fat diets, which strictly limit carbohydrate consumption (less than 40g / day) and allow unlimited consumption of high-fat foods, such as pork belly, butter, coconuts oils, fat meat, eggs and cheese, etc… (cf appendix A). Patients will be provided with 2 meals (lunch and dinner), every meal with 2 dishes (first course and main course) and bread for every day for 3 months (ELIOR partnership).

Dietary Supplement: Continuous ketogenic diet

B

EXPERIMENTAL

patients will be asked to follow in a discontinuous way (15 days on, 15 days off) a very low-carbohydrate, high-fat diets, which strictly limit carbohydrate consumption (less than 40g / day) and allow unlimited consumption of high-fat foods, such as pork belly, butter, coconuts oils, fat meat, eggs and cheese…etc (cf appendix A). Patients will be provided with 2 meals (lunch and dinner), every meal with 2 dishes (first course and main course) and bread for every day for the ketogenic diet period for 3 months (ELIOR partnership).

Dietary Supplement: Discontinuous ketogenic diet

C

EXPERIMENTAL

patients will receive oral liquid ketone supplement BHB monoester, 2 tablespoons three times per day (depending on patient weight: at least 1g/kg weight body/day) 15 days-on 15 days off during 3 months. We would recommend taking it at least 30 to 60 min before meal times and they will receive standard diet (without any diet restrictions).

Dietary Supplement: beta-hydroxybutyrate (BHB) supplementation

D

NO INTERVENTION

patients will receive standard diet (without any diet restrictions) and be followed up as in arms A, B, C.

Interventions

Continuous ketogenic diet DIETARY_SUPPLEMENT

ARM A : continuous ketogenic diet

A

Discontinuous ketogenic diet DIETARY_SUPPLEMENT

ARM B : discontinuous ketogenic diet

B

beta-hydroxybutyrate (BHB) supplementation DIETARY_SUPPLEMENT

ARM C : BHB supplementation

C

Eligibility Criteria

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

You may qualify if:

• Adult men and women ≥ 18 years
• Patients with a histologically confirmed Renal Cell Carcinoma with a clear-cell component, sarcomatoid or rhabdoid
• Patients with metastatic (AJCC stage IV) Renal Cell Carcinoma, with at least one measurable lesion by CT Scan or MRI according to RECIST 1.1 or with clinically apparent disease that can be reliably monitored by the investigator
• Patients who have not received a prior systemic therapy. Prior cytokine therapies (e.g. interleukine-2, interferon-α), vaccine therapy are allowed.
• Patients with Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
• Intermediate or poor risk group patients measured by the IMDC model
• Patients with brain metastases will be eligible if they are: asymptomatic, without edema, not on corticosteroids more than 10 mg per day or already treated
• Patients treated with radiation therapy will be eligible if they are: palliative, on focal radiation therapy, on immunosuppressive doses of systemic corticosteroids less than 10 mg per day.
• Patient should understand, sign, and date the written informed consent form prior to any protocol-specific procedures performed
• Patient should be able and willing to comply with study visits and procedures as per protocol
• Patients must be affiliated to a social security system or beneficiary of the same
• Women of childbearing potential must have a negative serum pregnancy test done within 24 hours prior to diet initiation. Potentially reproductive patients must agree to use an effective contraceptive method or practice adequate methods of birth control or practice complete abstinence while on treatment with Nivolumab and Ipilimumab
• Women who are breastfeeding should discontinue nursing prior to the first dose of study drug and until 6 months after the last dose

You may not qualify if:

• Weight loss \> 5% in the last month
• Weight loss \> 10% during last 6 months
• Albumin \<30 g/l
• Known or underlying medical condition (e.g., a condition associated with diarrhea or acute diverticulitis) that, in the investigator's opinion, would make the administration of study drug hazardous to the patient or obscure the interpretation of toxicity determination or adverse events.
• Fatty acid oxidation disturbances
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements as determined by study team members.
• Failure to submit to study clinical and biological follow-up for medical, geographic or social reasons
• Pregnant or breastfeeding women
• Patient under guardianship or deprived of his liberty by a judicial or administrative decision or incapable of giving his consent
• Known drug or alcohol abuse
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of systemic immunosuppressive therapy within 7 days prior to the first dose of study treatment (except local/topical or aerosol steroids)
• Has a known history of active tuberculosis (Mycobacterium tuberculosis)
• Has had a prior monoclonal antibody within 4 weeks or 5 half-life time (whichever is shorter) prior to the first dose of study treatment or who has not recovered (i.e., ≥ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Has an active autoimmune / immune mediated inflammatory disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjörgen's syndrome will not be excluded from the study.
• Has evidence of interstitial lung disease or active, non-infectious pneumonitis

Sponsors & Collaborators

• Gustave Roussy, Cancer Campus, Grand Paris: lead

Study Sites (3)

Gustave Roussy

Villejuif, Val-de-Marne, 94805, France

Location

Hôpital Européen Georges Pompidou

Paris, 75015, France

Location

Hôpitaux Cochin-Port-Royal

Paris, 75679, France

Location

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MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

3-Hydroxybutyric Acid; Dietary Supplements

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Hydroxybutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Ketone Bodies; Ketones; Fatty Acids, Volatile; Fatty Acids; Lipids; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• Emeline COLOMBA BLAMEBLE, MD

  Gustave Roussy, Cancer Campus, Grand Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients will be included sequentially in each arm from arm A to arm D. When the first inclusion arm A will be full with 15 patients who passed the screening, then next patients will be enrolled in arm B, then it will be the same process with arm C and last patients will be included in arm D. However, the clinician has the option of including the patient in the standard diet arms with or without BHB (arm C or D), instead of the ketogenic diet arms (arm A or B), if the patient's organizational constraints do not allow for a strict ketogenic diet.

Study Record Dates

• First Submitted: October 21, 2021
• First Posted: November 12, 2021
• Study Start: March 24, 2023
• Primary Completion: May 22, 2024
• Study Completion: May 22, 2024
• Last Updated: December 5, 2024

Record last verified: 2024-12

Locations

FR (3)