Study Evaluating the Ketogenic Diet in Patients With Metastatic Pancreatic Cancer

Sponsor

Translational Drug Development (Other)

Overall Status

Recruiting

CT.gov ID

NCT04631445

Collaborator

Translational Genomics Research Institute (Other)

Enrollment

Locations

Arms

29.9

Anticipated Duration (Months)

5.7

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will evaluate the effects of the ketogenic diet in patients with metastatic pancreatic cancer while receiving chemotherapy.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Pancreatic Ductal Adenocarcinoma	Other: Ketogenic Diet	N/A

Detailed Description

A randomized, phase II trial designed to evaluate the progression free survival in patients with metastatic pancreatic cancer on triplet therapy (nab-paclitaxel + gemcitabine + cisplatin) while on ketogenic diet or non-ketogenic diet. This study also aims to compare the changes in serum metabolites and quality of life between the two arms.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Ketogenic diet with standard of care chemotherapy versus non-ketogenic diet with standard of care chemotherapyKetogenic diet with standard of care chemotherapy versus non-ketogenic diet with standard of care chemotherapy

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Randomized Phase II Trial of Two Different Nutritional Approaches for Patients Receiving Treatment for Their Advanced Pancreatic Cancer

Actual Study Start Date :

Dec 2, 2020

Anticipated Primary Completion Date :

Mar 1, 2023

Anticipated Study Completion Date :

Jun 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ketogenic (KD) + Triplet Ketogenic diet plus nab-paclitaxel 125 mg/m2, cisplatin 25 mg/m2, and gemcitabine 1000 mg/m2 all administered intravenously (IV) on Days 1 and 8 every 21 days.	Other: Ketogenic Diet Ketogenic diet (KD) will consist of macros: dietary carbohydrates restricted to < 30 g/day; daily protein intake will be targeted to 1.5 g/kg/day (targeted to ideal body weight).
No Intervention: Non-ketogenic + Triplet Non-ketogenic diet plus nab-paclitaxel 125 mg/m2, cisplatin 25 mg/m2, and gemcitabine 1000 mg/m2 all administered intravenously (IV) on Days 1 and 8 every 21 days.

Arm

Intervention/Treatment

Experimental: Ketogenic (KD) + Triplet

Ketogenic diet plus nab-paclitaxel 125 mg/m2, cisplatin 25 mg/m2, and gemcitabine 1000 mg/m2 all administered intravenously (IV) on Days 1 and 8 every 21 days.

Other: Ketogenic Diet

Ketogenic diet (KD) will consist of macros: dietary carbohydrates restricted to < 30 g/day; daily protein intake will be targeted to 1.5 g/kg/day (targeted to ideal body weight).

No Intervention: Non-ketogenic + Triplet

Non-ketogenic diet plus nab-paclitaxel 125 mg/m2, cisplatin 25 mg/m2, and gemcitabine 1000 mg/m2 all administered intravenously (IV) on Days 1 and 8 every 21 days.

Outcome Measures

Primary Outcome Measures

Progression-free survival per RECIST 1.1 [36 months]
Progression-free survival (PFS) is defined as the time from randomization to first documentation of objective tumor progression or to death due to any cause.

Secondary Outcome Measures

To compare the number of responses by RECIST 1.1 [36 months]
To compare the number of complete responses/partial responses as defined by CT scan using the Response Evaluation Criteria In Solid Tumors 1.1 (RECIST 1.1) and CA 19-9 (or CA 125, or CEA if not expressers of CA 19-9) down to normal limits (from at least > 2X ULN).
To compare the disease control rate using the Response Evaluation Criteria In Solid Tumors 1.1 (RECIST 1.1). [36 months]
(Partial Response + Complete Response + Stable Disease for at least 9 weeks)
Cancer Biomarkers [36 months]
Change in CA 19-9 (or CA 125, or CEA if not expressers of CA 19-9)
Cancer Biomarkers returning to normal [36 months]
Rates of normalization of CA 19-9 (or CA 125, or CEA if not expressers of CA 19-9)
Change in BMI [36 months]
To compare the average weight (kg), using BMI calculation (BMI = weight (kg) / height (m2))
Compare insulin levels [36 months]
To compare average insulin levels
To compare the average HbgA1c level [36 months]
To compare the average HbgA1c levels
To compare changes in serum metabolites [36 months]
To compare changes in serum metabolites
To compare quality of life between arms via the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire QLC-C30 (EORTC QLQ-C30) assessment. [36 months]
Higher scores in the quality of life on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire QLC-C30 (EORTC QLQ-C30) assessment may show a better outcome.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥ 18 years of age; male or female.
Histologically or cytologically confirmed metastatic pancreatic ductal adenocarcinoma, not previously treated for their metastatic disease.
Capable of providing informed consent and complying with trial procedures.
Karnofsky Performance Status (KPS) of ≥ 70%.
Life expectancy ≥ 12 weeks.
Measurable tumor lesions according to RECIST 1.1 criteria.
<Grade 2 pre-existing peripheral neuropathy per NCI CTCAE, Version 5.0.
Patient has acceptable coagulation status as indicated by an INR ≤1.5 times institutional upper limit of normal (ULN). Patients on anticoagulation can be included at the discretion of the investigator.
Patients must have normal organ and marrow function as defined below:

Absolute neutrophil count ≥1,500/mm3
Platelet concentration ≥100,000/mm3 with no platelet transfusions within 7 days prior to laboratory sample
Hemoglobin ≥ 9.0g/dL (PRBCs may be given to meet this criteria)
Hematocrit level ≥ 27%
Total bilirubin within 1.25 x ULN
AST (SGOT) and ALT (SGPT) ≤ 2.5 times upper limit of normal (if liver metastases are present, then ≤ 5 x ULN is allowed)
Serum creatinine < 1.5 mg/dL.

Patient must have a Smartphone or computer in order to work with Virta
Females of child-bearing potential (defined as a sexually mature woman who (1) has not undergone hysterectomy [the surgical removal of the uterus] or bilateral oophorectomy [the surgical removal of both ovaries] or (2) has not been naturally postmenopausal for at least 24 consecutive months [i.e., has had menses at any time during the preceding 24 consecutive months]) must:
Either commit to true abstinence* from heterosexual contact (which must be reviewed on a monthly basis), or agree to use, and be able to comply with, effective contraception without interruption, 28 days prior to starting IP therapy (including dose interruptions), and while on study medication or for a longer period if required by local regulations following the last dose of IP; and
Have a negative serum pregnancy test (β -hCG) result at screening and agree to ongoing pregnancy testing during the course of the study, and after the end of study therapy. This applies even if the subject practices true abstinence* from heterosexual contact.
Male subjects must practice true abstinence* or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for 6 months following discontinuation from study treatment, even if he has undergone a successful vasectomy.

True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. [Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception].

Exclusion Criteria:

Patients must have received no previous radiotherapy, surgery, chemotherapy or investigational therapy for the treatment of their metastatic pancreatic disease. Prior treatment in the adjuvant setting with chemotherapy and radiation are allowed, provided at least 6 months have elapsed since completion of the last therapy and recurrence and no lingering toxicities are present (this will be first line treatment for metastatic disease).
Evidence of central nervous system (CNS) metastasis (negative imaging study, if clinically indicated, within 4 weeks of Screening Visit).
History of other malignancies (except cured basal cell carcinoma, superficial bladder cancer or carcinoma in situ of the cervix) unless documented free of cancer for ≥ 2 years.
Uncontrolled intercurrent illness, including but not limited to New York Heart Association Class III or IV, myocardial infarction within the past 6 months, or unstable arrhythmia.
Known infection with HIV, hepatitis B, or hepatitis C.
Active, uncontrolled bacterial, viral, or fungal infections, requiring systematic therapy.
Major surgery within 4 weeks prior to study entry. (Port-a-cath may be inserted during this time period).
Any condition in the opinion of the principal investigator that might interfere with the patient's participation in the study or in the evaluation of the study results.
Any condition in the opinion of the principal investigator that is unstable and could jeopardize the patient's participation in the study.
Unwillingness or inability to comply with procedures required in this protocol, including unwillingness to follow a ketogenic diet.
Severe malnutrition or body mass index (BMI) < 18.
Albumin < 3.0 g/dL.
History of Type 1 diabetes.
History of diabetic ketoacidosis (DKA).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Honor Health	Scottsdale	Arizona	United States	85258
2	USC/Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
3	Nuvance Health-Danbury Hospital	Danbury	Connecticut	United States	06810
4	Nuvance Health	Norwalk	Connecticut	United States	06856
5	Atlantic Health System	Morristown	New Jersey	United States	07962
6	South Texas Accelerated Research Therapeutics, LLC	San Antonio	Texas	United States	78229
7	Baylor Scott and White	Temple	Texas	United States	76508