Medical Food for the Dietary Management of Metastatic Pancreatic Cancer

• ClinicalTrials.gov Identifier: NCT05078775
• Recruitment Status: Recruiting
• First Posted: October 14, 2021
• Last Update Posted: October 14, 2021
• Sponsor: Faeth Therapeutics
• Information provided by (Responsible Party): Faeth Therapeutics

Study Description

Brief Summary:

This is a single arm study evaluating the tolerability and markers of pancreatic cancer with a specially designed medical food restricted in specific amino acids for the dietary management of subjects with metastatic pancreatic adenocarcinoma. Subjects will be receiving two FDA approved first line drug therapies, gemcitabine and nab-paclitaxel (gem+nabP), that are routinely prescribed in combination for metastatic pancreatic cancer as part of their routine care.

Condition or disease	Intervention/treatment	Phase
Metastatic Pancreatic Cancer	Other: NEAAR Medical Food	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 60 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Prospective, Single Arm Medical Food Study to Evaluate a Standardized Nonessential Amino Acid Restriction (NEAAR) Medical Food for the Dietary Management of Metastatic Pancreatic Cancer
• Estimated Study Start Date: October 2021
• Estimated Primary Completion Date: August 2023
• Estimated Study Completion Date: August 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Nonessential Amino Acid Restriction (NEAAR) Medical Food; This is a single arm study in which all subjects will receive NEAAR medical food and standard of care FDA approved chemotherapy. Each week NEAAR medical food will be consumed 5 consecutive days followed by 2 days of habitual food.	Other: NEAAR Medical Food; All subjects will receive NEAAR Medical Food, a standardized non-essential amino acid restricted medical food, and will also receive standard of care FDA approved chemotherapy consisting of gemcitabine and nab-paclitaxel.

Outcome Measures

Primary Outcome Measures :

1. Demonstrate tolerability of the NEAAR medical food. [ Time Frame: Through study completion, average of 6 months ]
   The primary endpoint is the rate of the most common Grade 3 and 4 adverse event (AE) related to the NEAAR medical food (when added to standard of care chemotherapy) regimen. This will be compared with the rate of the most common Grade 3 and 4 AE of the historical control (i.e. standard of care).

Secondary Outcome Measures :

1. Comparison of gene mutation and gene expression as predictors of management of disease with the NEAAR medical food, assessed in relation to: [ Time Frame: Through study completion, average of 6 months ]
   Absolute and relative change of biomarkers of interest (CA19-9, CEA, and CA125)
2. Comparison of gene mutation and gene expression as predictors of management of disease with the NEAAR medical food, assessed in relation to: [ Time Frame: Through study completion, average of 6 months ]
   Overall Response Rates using RECIST 1.1
3. Comparison of gene mutation and gene expression as predictors of management of disease with the NEAAR medical food, assessed in relation to: [ Time Frame: Through study completion, average of 6 months ]
   Progression-free Survival using RECIST 1.1
4. Comparison of gene mutation and gene expression as predictors of management of disease with the NEAAR medical food, assessed in relation to: [ Time Frame: Through study completion, average of 6 months ]
   Overall survival
5. Establish the impact of NEAAR medical food on ECOG (Eastern Cooperative Oncology Group) performance status and weight compared to historical controls [ Time Frame: Through study completion, average of 6 months ]
   ECOG Performance Status will be measured utilizing the ECOG performance status scale
6. Establish all plasma amino acid concentrations (nmol/mL) for the time period the subject is consuming NEAAR medical food and compare with baseline measurements. [ Time Frame: Through study completion, average of 6 months ]
7. Correlation and regression analysis with blood amino acid concentrations (nmol/mL) for: [ Time Frame: Through study completion, average of 6 months ]
   L-glutamine, L-glutamic acid, L-alanine, glycine, L-arginine, L-proline, L-aspartic acid, L-serine, L-asparagine, L-tyrosine, L-cysteine/L-cystine, L-lysine, L-valine, L-histidine, L-leucine, L-isoleucine, L-tryptophan, L-phenylalanine, L-methionine, L-threonine.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Subjects presenting with histologically or cytologically confirmed metastatic pancreatic adenocarcinoma diagnosed within 6 weeks prior to screening.
2. Subjects are eligible for and being scheduled to begin standard of care treatment with the gem+nabP regimen.
3. Subjects who are 18 years of age or older.
4. Subjects are capable of giving signed informed consent.
5. Females of child-bearing potential (defined as a sexually mature woman who has not undergone hysterectomy or bilateral oophorectomy or 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:
6. Commit to true abstinence from heterosexual contact or agree to use, and be able to comply with, effective contraception without interruption until their final study visit and return to habitual food; and
7. have a negative serum pregnancy test (β -hCG) result at screening. This applies even if the subject practices true abstinence from heterosexual contact.
8. Male subjects must commit to practicing true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential starting at screening until discontinuation from study, even if he has undergone a successful vasectomy. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
9. Subjects with measurable disease as determined by RECIST 1.1.
10. ECOG Performance Status of ≤ 1.

11. Subject has adequate organ function during screening evaluations defined as all the following:

    1. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (1500/µL).
    2. Platelet count ≥ 100 x 109/L.
    3. Hemoglobin ≥ 9 g/dL.
    4. Activated partial thromboplastin time /international normalized ratio (aPTT/INR) ≤ 1.5 x upper limit of normal (ULN) unless the subject is on anticoagulants in which case therapeutically acceptable values (as determined by the investigator) meet eligibility requirements.
    5. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2.5 × ULN. In the case of known (i.e., radiological or biopsy documented) liver metastasis, serum transferase levels must be ≤ 5 x ULN.
    6. Total serum bilirubin ≤ 1.5 x ULN (except for subjects with known Gilbert's Syndrome for which ≤ 3 x ULN is permitted).
    7. Serum creatinine < 2.0 x ULN and creatinine clearance ≥ 50 mL/min/1.73m2.
    8. Serum albumin ≥ 3.5mg/dL.
12. Subjects must express elevated levels of carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), and/or carbohydrate antigen 125 (CA125) during screening.
13. Subjects must have normal Vitamin D levels or be willing to start Vitamin D supplementation during the NEAAR medical food period.
14. Subjects must have available pancreatic adenocarcinoma tissue samples from a primary or metastatic site that has been biopsied within the last 6 months and provide consent for them to be obtained and analyzed by the study sponsor to assist in determining eligibility. A minimum of five (ten preferred) formalin fixed paraffin embedded (FFPE) archival or fresh tumor tissue slides are required.
15. Confirmation of low expression of specific enzymes as assessed by immunohistochemical (IHC) assay on the FFPE archival or fresh tumor tissue slides provided by the site.
16. Subjects must be willing to stop taking any supplements, herbal medicines, or alternative remedies or other prescribed or over the counter supplements for at least 1 week prior to Cycle 1 Day 1 of gem+nabP and through the NEAAR medical food period.
17. Subjects either have normal pancreatic function or are already taking Pancreatic Enzyme Replacement Therapy (PERT). If pancreatic insufficiency status is unknown, subjects must have a fecal elastase test to check for moderate or severe pancreatic insufficiency. Subjects with diagnosed pancreatic insufficiency must take PERT.

Exclusion Criteria:

1. Any prior neoadjuvant or adjuvant therapy for pancreatic cancer within 6 months of screening.
2. Comorbidity risk, that in the discretion of the investigator would make the subject a poor candidate for the NEAAR medical food.
3. Diagnosis of another malignancy within the past 2 years (excluding a history of carcinoma in situ of the cervix, superficial non-melanoma skin cancer, or superficial bladder cancer that has been adequately treated, or stage 1 prostate cancer that does not require treatment or requires only treatment with luteinizing hormone-releasing hormone agonists or antagonists if initiated at least 30 days prior to beginning the NEAAR medical food).
4. A body mass index (BMI) <20 kg/m2 or >40 kg/m2 or, serious or refractive cachexia or anorexia that, in the investigator's opinion, realistically prohibits subjects from having energy or appetite sufficient to reliably engage in a strict medical food regimen for an extended time.
5. Insulin-dependent diabetes.
6. Subjects who must take medications that impact amino acid levels
7. Inability or unwillingness to comply with study and/or follow-up procedures, or medical food modifications described in the protocol.
8. Presence of any significant comorbidity including clinically significant cardiac disease (e.g., congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias not well controlled with medication), myocardial infarction or unstable angina within the 12 months prior to screening, or any major organ failure.
9. Known hypersensitivity, intolerance, or religious restrictions regarding pork or pork-derived products or to any of the components of the medical food modification, gemcitabine or nab-paclitaxel, PERT products (e.g., Pancreaze), or formulary excipients in these products.
10. Untreated clinically significant hyperlipidemia per investigator.
11. Subjects with a condition (including gallbladder disease and/or fatty acid oxidation disorders) where high-fat or fatty food is contraindicated.
12. Any non-cancerous co-existing condition that could elevate CA19-9, CEA, or CA125.
13. Presence of central nervous system or brain metastases that are not controlled under treatment as assessed by the investigator.
14. Presence of any condition (e.g., persistent diarrhea) that renders the subject unable to satisfactorily chew, swallow, digest, or tolerate the majority of foods and liquids of the NEAAR medical food.
15. Taking or needs to take any protein or amino acid containing nutritional supplements (e.g., Ensure®).
16. Women who are, plan to be, or may potentially be pregnant or lactating.
17. Lack of physical integrity of the upper or lower gastrointestinal (GI) tract.
18. Known, existing uncontrolled coagulopathy.
19. Major surgery or significant traumatic injury within 14 days of planned start of NEAAR medical food or the anticipation of the need for a major surgical procedure during the study.
20. Active, clinically significant, uncontrolled bacterial, viral, or fungal infection(s).
21. Known current infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.
22. History of confirmed food allergy.
23. Currently enrolled in any other investigational trial or treatment with investigational therapy(ies).
24. Diagnosed with an eating disorder, irritable bowel syndrome (IBS), Crohn's disease, ulcerative colitis, or gluten-sensitive enteropathy.

Contacts and Locations

Contacts

Contact: Katelyn Patterson, BS; 415-234-0538; katelyn@faeththerapeutics.com

Contact: Todd Young, MD; 650-515-7886; todd@faeththerapeutics.com

Locations

United States, New Jersey

Atlantic Health; Recruiting

Morristown, New Jersey, United States, 07962

Contact: Nancy Ginder, RN, BSN 973-971-6608 Nancy.Ginder@atlantichealth.org

Principal Investigator: Angela Alistar, MD

Sponsors and Collaborators

Faeth Therapeutics

Investigators

• Principal Investigator: Andrew Hendifar, MD; Cedars-Sinai

More Information

• Responsible Party: Faeth Therapeutics
• ClinicalTrials.gov Identifier: NCT05078775
• Other Study ID Numbers: NEAAR-001
• First Posted: October 14, 2021
• Last Update Posted: October 14, 2021
• Last Verified: October 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Pancreatic Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases