A Pilot Study Evaluating a Ketogenic Diet Concomitant to Nivolumab and Ipilimumab in Patients With Metastatic Renal Cell Carcinoma
NCT ID: NCT05119010
Last Updated: 2024-12-05
Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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Recruitment Status
TERMINATED
Clinical Phase
NA
Total Enrollment
3 participants
Study Classification
INTERVENTIONAL
Study Start Date
2023-03-24
Study Completion Date
2024-05-22
Brief Summary
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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.
Detailed Description
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After being informed about the study and potential risks, all patients giving informed consent will undergo a 10 days screening period to determine eligibility for study entry. At week1day1, patients who meet the eligibility requirements will be enrolled in to :
* Arm A : continuous ketogenic diet for 3 months
* Arm B : discontinuous ketogenic diet (15 days on, 15 days off) for 3 months
* Arm C : oral liquid ketone supplement BHB monoester, 15 days-on 15 days off during 3 months.
* Arm D : standard diet (without any diet restrictions). and follow up as in arms A, B, C.
All patients will receive Nivolumab plus Ipilimumab according to practical routine.
* Arm A : continuous ketogenic diet for 3 months
* Arm B : discontinuous ketogenic diet (15 days on, 15 days off) for 3 months
* Arm C : oral liquid ketone supplement BHB monoester, 15 days-on 15 days off during 3 months.
* Arm D : standard diet (without any diet restrictions). and follow up as in arms A, B, C.
All patients will receive Nivolumab plus Ipilimumab according to practical routine.
Conditions
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Metastatic Renal Cell Carcinoma
Study Design
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Allocation Method
NON_RANDOMIZED
Intervention Model
PARALLEL
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.
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.
Primary Study Purpose
TREATMENT
Blinding Strategy
NONE
Study Groups
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A
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).
Group Type
EXPERIMENTAL
Continuous ketogenic diet
Intervention Type
DIETARY_SUPPLEMENT
ARM A : continuous ketogenic diet
B
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).
Group Type
EXPERIMENTAL
Discontinuous ketogenic diet
Intervention Type
DIETARY_SUPPLEMENT
ARM B : discontinuous ketogenic diet
C
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).
Group Type
EXPERIMENTAL
beta-hydroxybutyrate (BHB) supplementation
Intervention Type
DIETARY_SUPPLEMENT
ARM C : BHB supplementation
D
patients will receive standard diet (without any diet restrictions) and be followed up as in arms A, B, C.
Group Type
NO_INTERVENTION
No interventions assigned to this group
Interventions
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Continuous ketogenic diet
ARM A : continuous ketogenic diet
Intervention Type
DIETARY_SUPPLEMENT
Discontinuous ketogenic diet
ARM B : discontinuous ketogenic diet
Intervention Type
DIETARY_SUPPLEMENT
beta-hydroxybutyrate (BHB) supplementation
ARM C : BHB supplementation
Intervention Type
DIETARY_SUPPLEMENT
Eligibility Criteria
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Inclusion Criteria
1. Adult men and women ≥ 18 years
2. Patients with a histologically confirmed Renal Cell Carcinoma with a clear-cell component, sarcomatoid or rhabdoid
3. 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
4. Patients who have not received a prior systemic therapy. Prior cytokine therapies (e.g. interleukine-2, interferon-α), vaccine therapy are allowed.
5. Patients with Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
6. Intermediate or poor risk group patients measured by the IMDC model
7. 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
8. 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.
9. Patient should understand, sign, and date the written informed consent form prior to any protocol-specific procedures performed
10. Patient should be able and willing to comply with study visits and procedures as per protocol
11. Patients must be affiliated to a social security system or beneficiary of the same
12. 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
13. Women who are breastfeeding should discontinue nursing prior to the first dose of study drug and until 6 months after the last dose
2. Patients with a histologically confirmed Renal Cell Carcinoma with a clear-cell component, sarcomatoid or rhabdoid
3. 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
4. Patients who have not received a prior systemic therapy. Prior cytokine therapies (e.g. interleukine-2, interferon-α), vaccine therapy are allowed.
5. Patients with Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
6. Intermediate or poor risk group patients measured by the IMDC model
7. 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
8. 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.
9. Patient should understand, sign, and date the written informed consent form prior to any protocol-specific procedures performed
10. Patient should be able and willing to comply with study visits and procedures as per protocol
11. Patients must be affiliated to a social security system or beneficiary of the same
12. 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
13. Women who are breastfeeding should discontinue nursing prior to the first dose of study drug and until 6 months after the last dose
Exclusion Criteria
1. Weight loss \> 5% in the last month
2. Weight loss \> 10% during last 6 months
3. Albumin \<30 g/l
4. 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.
5. Fatty acid oxidation disturbances
6. Uncontrolled diabetes defined as a hemoglobin A1C level \> 8%. Diabetes is not exclusionary provided the patient is not maintained with either oral medications or insulin.
7. 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.
8. Failure to submit to study clinical and biological follow-up for medical, geographic or social reasons
9. Pregnant or breastfeeding women
10. Patient under guardianship or deprived of his liberty by a judicial or administrative decision or incapable of giving his consent
11. Known drug or alcohol abuse
12. 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)
13. Has a known history of active tuberculosis (Mycobacterium tuberculosis)
14. 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.
15. 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.
16. Has evidence of interstitial lung disease or active, non-infectious pneumonitis
17. Has an active infection requiring systemic therapy
18. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
19. Positive for Human Immunodeficiency Virus (HIV) antibody testing
20. Active or chronic hepatitis C and/or B infection. Patients with past/resolved HBV infection (defined as the presence of anti-hepatitis B core antibody, IgG anti-HBs +) are eligible. Hepatitis B virus DNA should be obtained in these patients prior to the first dose of study treatment. Patients positive for hepatitis C virus antibody are eligible only if PCR is negative for HCV RNA
21. Patients with altered hematopoietic or organ function, as indicated by the following criteria (assessed within 5 days prior registration):
* White blood cell \< 3000/μL
* Polynuclear neutrophils \< 1.5 x 109/L
* Platelets \< 100 x 109/L
* Hemoglobin \< 7.0 g/mL
* Alanine aminotransferase/aspartate aminotransferase \> 3.0 x ULN in the absence of liver metastases or \> 5x upper limit of normal in the presence of liver metastases
* Bilirubin \> 1.5 x ULN (except Gilbert Syndrome: \< 3.0 mg/dL)
* Creatinine clearance ≤ 35 mL/min (measured or calculated by Cockcroft and Gault formula)
2. Weight loss \> 10% during last 6 months
3. Albumin \<30 g/l
4. 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.
5. Fatty acid oxidation disturbances
6. Uncontrolled diabetes defined as a hemoglobin A1C level \> 8%. Diabetes is not exclusionary provided the patient is not maintained with either oral medications or insulin.
7. 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.
8. Failure to submit to study clinical and biological follow-up for medical, geographic or social reasons
9. Pregnant or breastfeeding women
10. Patient under guardianship or deprived of his liberty by a judicial or administrative decision or incapable of giving his consent
11. Known drug or alcohol abuse
12. 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)
13. Has a known history of active tuberculosis (Mycobacterium tuberculosis)
14. 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.
15. 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.
16. Has evidence of interstitial lung disease or active, non-infectious pneumonitis
17. Has an active infection requiring systemic therapy
18. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
19. Positive for Human Immunodeficiency Virus (HIV) antibody testing
20. Active or chronic hepatitis C and/or B infection. Patients with past/resolved HBV infection (defined as the presence of anti-hepatitis B core antibody, IgG anti-HBs +) are eligible. Hepatitis B virus DNA should be obtained in these patients prior to the first dose of study treatment. Patients positive for hepatitis C virus antibody are eligible only if PCR is negative for HCV RNA
21. Patients with altered hematopoietic or organ function, as indicated by the following criteria (assessed within 5 days prior registration):
* White blood cell \< 3000/μL
* Polynuclear neutrophils \< 1.5 x 109/L
* Platelets \< 100 x 109/L
* Hemoglobin \< 7.0 g/mL
* Alanine aminotransferase/aspartate aminotransferase \> 3.0 x ULN in the absence of liver metastases or \> 5x upper limit of normal in the presence of liver metastases
* Bilirubin \> 1.5 x ULN (except Gilbert Syndrome: \< 3.0 mg/dL)
* Creatinine clearance ≤ 35 mL/min (measured or calculated by Cockcroft and Gault formula)
Minimum Eligible Age
18 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
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Gustave Roussy, Cancer Campus, Grand Paris
OTHER
Sponsor Role
lead
Responsible Party
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Responsibility Role
SPONSOR
Principal Investigators
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Emeline COLOMBA BLAMEBLE, MD
Role: PRINCIPAL_INVESTIGATOR
Gustave Roussy, Cancer Campus, Grand Paris
Locations
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Gustave Roussy
Villejuif, Val-de-Marne, France
Site Status
Hôpital Européen Georges Pompidou
Paris, , France
Site Status
Hôpitaux Cochin-Port-Royal
Paris, , France
Site Status
Countries
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France
References
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Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
2020/3206
Identifier Type: OTHER
Identifier Source: secondary_id
2020-A03550-39
Identifier Type: -
Identifier Source: org_study_id