Ketogenic Diet in Evaluating Metabolomic and Tissue Effects in Overweight or Obese Patients with Stage I-IVA Endometrial Cancer

Status: Active

Description

This randomized pilot clinical trial studies how well a ketogenic diet works in evaluating metabolomic and tissue effects in overweight or obese patients with stage I-IVA endometrial cancer. Ketogenic diet may lower inflammation, bad cholesterol, insulin and blood sugar, and these changes may help to control signals in the body that could shrink endometrial cancer.

Eligibility Criteria

Inclusion Criteria

  • Patients must have a diagnosis endometrial carcinoma on a tissue sample obtained at MSK or WCMC (biopsy); patients with the following histologic epithelial cell types are eligible: endometrioid adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, adenocarcinoma not otherwise specified (N.O.S.), mucinous adenocarcinoma, squamous cell carcinoma, transitional cell carcinoma, carcinosarcoma
  • Patients must have consented to surgery with a board-certified gynecology (Gyn) surgeon
  • Patients must have no had adjuvant therapy for the management of endometrial carcinoma; this includes chemotherapy, chemotherapy and radiation therapy, and/or consolidation/maintenance therapy; chemotherapy administered in conjunction with primary radiation as a radio-sensitizer WILL be counted as a systemic chemotherapy regimen; this also pertains to hormonal, vascular, and targeted therapy for the management of endometrial cancer
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Patients with stage I-IVA are eligible
  • Absolute neutrophil count (ANC) >= 1.5 k/mcl (obtained within 10 days prior to first study treatment)
  • Platelet count >= 100 k/mcl (obtained within 10 days prior to first study treatment)
  • Hemoglobin >= 9.0 g/dL (obtained within 10 days prior to first study treatment)
  • Total bilirubin =< 1.5 x the upper limit of normal (ULN) (obtained within 10 days prior to first study treatment)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3.0 x ULN (obtained within 10 days prior to first study treatment)
  • Albumin >= 3.5 g/dL (obtained within 10 days prior to first study treatment)
  • Serum creatinine =< 1.5 x ULN OR creatinine clearance >= 50 mL/min on the basis of the Cockcroft-Gault glomerular filtration rate estimation (obtained within 10 days prior to first study treatment)
  • Glycosylated hemoglobin (HbA1c) =< 7.9 %
  • BMI >= 25 kg/m^2
  • Patients must agree to consent to the companion genomic profiling study MSK IRB 12-245
  • Patients must agree to consent for their tumor samples to be used for generation of cellular research tools such as organoids
  • Willingness to travel to the CTSC at WCMC weekly
  • Patient and/or legally authorized representative must have the ability to read, write, speak and understand English; note: If patient does not have the capability to read or write in English, the patient's preferred language should be English and the legally authorized representative (LAR) will be responsible for completing all study forms on the patient's behalf

Exclusion Criteria

  • History of diabetes and on active diabetes treatment with pharmacotherapy (oral hypoglycemics or insulin)
  • History of gout
  • History of myocardial infarction or unstable angina within 6 months prior to first study treatment
  • Active infection requiring antibiotics (with the exception of uncomplicated urinary tract infection)
  • New York Heart Association class II or greater congestive heart failure
  • Patients with a corrected QT (QTc) interval of > 450 milliseconds (msec) on screening electrocardiogram (ECG) for men or > 470 msec for women
  • History of malabsorption syndrome or other condition that would interfere with enteral absorption
  • Inability or unwillingness to swallow
  • Clinically significant history of liver disease, including cirrhosis and current alcohol abuse
  • Known active hepatitis infection
  • Known human immunodeficiency virus (HIV) infection
  • Need for current chronic corticosteroid therapy (>= 10 mg of prednisone per day or an equivalent dose of other anti-inflammatory corticosteroids)
  • Pregnancy, lactation, or breastfeeding
  • Patients of childbearing potential must have a negative pregnancy test within 10 days prior to treatment start to be eligible
  • Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease)
  • Major surgical procedure or significant traumatic injury within 28 days prior to day 1 or anticipation of the need for major surgery during the course of study treatment
  • Known untreated or active central nervous system (CNS) metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control); patients with a history of treated CNS metastases are eligible, provided that they meet all of the following criteria: * Presence of measurable disease outside the CNS * No radiographic evidence of worsening upon the completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study * No history of intracranial hemorrhage or spinal cord hemorrhage * No ongoing requirement for dexamethasone as therapy for CNS disease (anticonvulsants at a stable dose are allowed) * Absence of leptomeningeal disease
  • Inability to comply with study and follow-up procedures
  • Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the investigator’s opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
  • History of nephrolithiasis or nephrolithiasis including that incidentally discovered during computed tomography (CT) screening
  • Known selenium deficiency
  • Diagnosis of seizure disorder
  • Participation in a diet (Atkins, Weight Watchers, Best Life, Nutrisystem, South Beach, Jenny Craig, Paleo Diet, Zone etc) or weight loss plan within 28 days prior to day 1 of treatment
  • Severe constipation or condition where exacerbation of constipation is not advisable (e.g. small bowel obstruction history)
  • Planned vacation or dental work during the study phase
  • Vegetarian or vegan eating habits
  • History of muscle cramps or restless legs
  • Untreated or poorly controlled gastro-esophageal reflux disease
  • Gum chewing habit
  • An allergy or intolerance to egg, gluten or milk protein

Locations & Contacts

New York

New York
Memorial Sloan Kettering Cancer Center
Status: Active
Contact: Vicky Makker
Phone: 646-888-4224
West Harrison
Memorial Sloan Kettering Westchester
Status: Active
Contact: Vicky Makker
Phone: 646-888-4224

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To evaluate the feasibility of a ketogenic diet in pre-surgical endometrial cancer patients.

II. To assess rates of recruitment.

III. To assess eligibility criteria and demographics of the recruited population.

IV. To assess participant’s ability to:

IVa. Present for and complete scheduled laboratory assessments.

IVb. Obtain and complete meal assessments and completion records.

IVc. Complete quality of life (QOL) surveys.

V. To assess participants ability to obtain and consume ketogenic diet (KD) meals.

VI. To assess rates of:

VIa. Attrition.

VIb. Participant burden.

VIc. Ketosis in the study population in comparison to standard diet.

SECONDARY OBJECTIVES:

I. To prospectively evaluate ketogenic diet effects on serum fasting insulin, glucose, lipids, adipokines, and circulating mediators of inflammation.

II. To investigate effects of ketogenic diet on surgical pathology specimens compared to presurgical biopsy with regards to tumor grade, and expression of Ki67, phosphorylated (p)-S6, p-AKT, p-ERK, INSR, glucose transporter 1 (GLUT-1), and p signal transducer and activator of transcription (STAT) via immunohistochemistry probes on paraffin-embedded tissue.

III. To investigate body composition and tumor size.

IV. To evaluate weekly changes in host factors such body mass index (BMI) and blood pressure over period of study.

V. To investigate QOL via European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ)-C30 and supplemental EORTC QLQ-Endometrial Cancer Module (EN24) questionnaires pre-initiation and post completion of diet intervention.

VI. Proteomic and metabolomic testing of presurgical tumor biopsy and surgical pathology.

EXPLORATORY OBJECTIVES:

I. To molecularly profile presurgical tumor biopsy and surgical resection specimen using the Memorial Sloan Kettering (MSK)-Integrated Mutation Profiling of Actionable Cancer Targets (IMPACT) platform in an effort to evaluate for potential molecular changes in pre-surgical and surgical pathology.

II. Research grade messenger (m) ribonucleic acid (RNA) sequencing of presurgical fresh frozen tumor biopsy and fresh frozen surgical resection specimen using TruSeq Standard mRNA Library prep kit and HiSeq2500 Rapid Run will be performed (Weill Cornell Medical Center Institutional Review Board [IRB] Protocol 1305013903).

III. Tumor organoid establishment from presurgical fresh (in cases with enough material) and fresh surgical resection specimen will be established in the Englander Institute for Precision Medicine research laboratory according to internal standard operating procedures (SOP)’s (IRB Protocol 1305013903).

IV. Research grade whole exome sequencing (EXaCT-2) of fresh frozen surgical resection specimen using the HaloPlex System (Agilent) and HiSeq2500 will be performed (IRB Protocol 1305013903).

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I (KETOGENIC DIET): Patients consume KD meal plan prepared by Clinical Translational Science Center (CTSC) for 21-28 days (up to day 33 if required to accommodate surgery date). Patients then undergo surgery the day after conclusion of diet plan.

ARM II (STANDARD DIET): Patients consume their normal diet plan for 21-28 days (up to day 33 if required to accommodate surgery date). Patients also meet with dietitian from the CTSC at Weill Cornell Medical Center (WCMC) weekly and receive standard nutritional counseling from the CTSC. Patients then undergo surgery the day after conclusion of diet plan.

After completion of study, patients are followed up at 2-4 weeks.

Trial Phase & Type

Trial Phase

No phase specified

Trial Type

Treatment

Lead Organization

Lead Organization
Memorial Sloan Kettering Cancer Center

Principal Investigator
Vicky Makker

Trial IDs

Primary ID 17-396
Secondary IDs NCI-2017-01838
Clinicaltrials.gov ID NCT03285152