Brain Tumors, Colorectal Cancer, Endometrial Cancer, Ovarian Cancer, Sarcoma
Conditions
Keywords
Montelukast, Almonds/Almond oil, Specialized pro-resolving mediators, Tumor-associated macrophages, Lipid mediators, Colorectal cancer, Inflammation
Brief summary
The purpose of this study is to create a prospective investigation to examine the effects of montelukast, almonds/almond oil, and specialized pro-resolving mediators (SPMs) on lipid profiles and tumor-associated macrophages (TAMs) in cancer patients (colorectal cancer, sarcoma, brain tumors, endometrial cancer, and ovarian cancer). The focus will be on assessing changes in lipid mediator concentrations, TAM reprogramming, and immune cell function in treated versus untreated patients. It is hypothesized that montelukast will reduce the pro-inflammatory effects of leukotriene B4 (LTB4), while SPMs and almonds/almond oil will shift the balance toward pro-resolving mediators, enhancing anti-inflammatory and immune-stimulatory responses and reprogramming TAMs.
Detailed description
This prospective study investigates the effects of montelukast, almonds/almond oil, and specialized pro-resolving mediators (SPMs) on lipid profiles and tumor-associated macrophages (TAMs) in patients with colorectal cancer (CRC), sarcoma, brain tumors (BT), endometrial cancer (EC), and ovarian cancer (OvCa). Patients receiving these treatments will be compared to untreated controls, with tissue samples collected post-surgery for analysis. A cohort of patients who have undergone tumor resection will be included for the assessment of lipid mediator concentrations (approximately 65 arachidonic acid pathway lipids) and TAM reprogramming, with an emphasis on comparing treated and untreated groups. The study will also examine peripheral blood mononuclear cells (PBMCs) and plasma concentrations of lipid mediators before and after treatment, focusing on changes in PBMC function and phenotype. It is hypothesized that montelukast, an LTB4/ cysteinyl leukotriene receptor 1 (CYSLTR1) inhibitor, will reduce the pro-inflammatory effects of LTB4 in cancer tissues. Furthermore, it is anticipated that SPMs and almonds/almond oil will shift the lipid mediator balance toward pro-resolving mediators, enhancing anti-inflammatory responses, stimulating immune function, and reprogramming TAMs.
Interventions
Montelukast 10 Mg Oral Tablet daily
COMBINATION_PRODUCTMontelukast 10 Mg Oral Tablet and SPM 4 g
Montelukast 10 Mg Oral Tablet and SPM 4 g
DIETARY_SUPPLEMENTCold- Pressed Almond Oil 30 mL
Cold- Pressed Almond Oil 30 mL every morning
DIETARY_SUPPLEMENTSports Pro Resolve 4 g
Sports Pro Resolve 4 tabs (2 g) twice daily
DIETARY_SUPPLEMENTDouble Wood SPM 4 g
Double Wood SPM 4 tabs (2 g) twice daily
DIETARY_SUPPLEMENT20 California Sweet Almonds
10 California Sweet Almonds twice daily
OTHERNo Interventions
No study treatment other than the standard of care management.
Sponsors
University of South Florida
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Masking description
None (Open Label)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Newly diagnosed individuals with stages I-IV colorectal or ovarian cancer, grade 1 and 2 endometrial cancer, as well as those with brain tumors or sarcoma. 2. Participants scheduled for surgical intervention at least two (2) weeks from the day of enrollment. 3. Patients must be able to understand and willing to sign a written informed consent document for both this study and the University of South Florida (USF)/ Tampa General Hospital (TGH) Biorepository study (STUDY000356). 4. Age 18 or older.
Exclusion criteria
1. Inability to give consent due to a mental condition that makes the participant unable to understand the study's nature, scope, and possible consequences. 2. Participants who are unlikely to adhere to the protocol as determined by the study investigator. 3. Allergy to fish, seafood, aspirin, NSAIDs, montelukast, or nuts 4. Participants with a history of asthma or chronic obstructive pulmonary disease (COPD). 5. Patients with a history of phenylketonuria (PKU). 6. Participants with a history of a psychiatric illness (e.g., major depression, anxiety disorder, bipolar disorder, obsessive-compulsive disorder, etc.). 7. Surgical intervention scheduled more than eight (8) weeks from the initial enrollment day. 8. No evidence of a discrete mass on endoscopy or radiologic imaging 9. Concomitant existence of other malignancies 10. Uncontrolled hypertension or diabetes mellitus 11. Chronic Liver Disease or cirrhosis 12. Liver function impairment or persisting elevations (confirmed by retest) of alanine aminotransferase (ALT), aspartate aminotransferase (AST), or direct bilirubin greater than 2x the upper limit of the normal range (ULN) 13. Bleeding conditions such as disorders of platelet function, idiopathic thrombocytopenia purpura (ITP), thrombotic thrombocytopenic purpura (TTP), hemophilia or any clotting factor deficiency, von Willebrand disease or Glanzmann disease among other 14. Use of antiplatelet or anticoagulant medications, including aspirin, clopidogrel, warfarin, direct oral anticoagulants (DOACs), and heparin, among others 15. Persistent significant or severe infection, either acute or chronic 16. Participants with significantly impaired bone marrow function or significant anemia, leukopenia, or thrombocytopenia (confirmed by retest): 1. Hematocrit \< 35% and/or 2. Absolute white blood cell count \< 3000 cells/mm3 (μL) and/or 3. Platelet count \< 150 000 cells/mm3 (μL) and/or 4. Absolute neutrophil ≤ 1500 cells/mm3 (μL) 17. Chronic use of immunosuppressive medications 18. History of organ transplantation 19. Emergency surgery 20. Pregnant or breast-feeding women or those who plan to become pregnant during the study. 21. Women of childbearing potential who are not protected by effective contraceptive methods of birth control and/or are unwilling or unable to be tested for pregnancy. 22. Prisoners 23. Participants who have received treatment with leukotriene inhibitors, taken omega-3 supplements, or eaten almonds within the last 4 weeks. 24. Prior use of any investigational drug in the preceding six (6) months 25. Participants who, after being enrolled in this study and assigned a particular study treatment, consume products involved in other study cohorts other than what they were assigned (i.e. if a patient is assigned to take SPMs as their study treatment but during the course of the study also is consuming daily almonds) 26. Participants who are unable to swallow oral medication or chew almonds. 27. Participants who have already started neoadjuvant therapies for their cancer diagnosis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Quantity of lipid mediators in a tumor specimen after 2 weeks of study treatment. | Day 14 of treatment | Quantitation will be assessed using liquid chromatography tandem mass spectrometry (LC-MS/MS). The absolute quantity of these lipid mediators will be compared to the absolute quantity in the corresponding normal tissue. In preliminary studies, the investigators have used LC-MS/MS to measure \ 65 different lipid mediators of the arachidonic acid pathway in colorectal cancer. Interestingly, the investigators found high proportions of pro-inflammation mediators and depressed levels of pro-resolution-of-inflammation mediators in cancer tissue compared with the non-affected tissue of the same patients. Possible study treatments include: specialized pro-resolving mediators vs Montelukast vs almonds/almond oil vs combination). |
| Quantity of lipid mediators in a non-cancerous (i.e. normal) tissue from the resected surgical specimen after 2 weeks of study treatment. | Day 14 of treatment | Quantitation will be assessed using liquid chromatography tandem mass spectrometry (LC-MS/MS). The absolute quantity of these lipid mediators will be compared to the absolute quantity in the corresponding cancer tissue. This change in quantity will enable us to make deductions about the influence of the corresponding study treatment on the tumor and its environment. For example, does the treatment in question make the tumor environment less inflamed/promote healing and therefore make the cancer more susceptible to treatment? Possible study treatments include: specialized pro-resolving mediators vs Montelukast vs almonds/almond oil vs combination). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quantity of tumor microenvironment subpopulations in a tumor specimen versus corresponding normal tissue after 2 weeks of study treatment. | Day 14 of treatment | Tumor microenvironment subpopulations are defined as the various components of the immune system in the tissue surrounding a cancer, i.e.: cluster of differentiation 4 (CD4) T cells, cluster of differentiation 8 (CD8) T cells, B cells, natural killer (NK) cells, macrophages, etc. Quantitation will be assessed using n-counter analysis. |
| Distribution of tumor-associated macrophage (TAM) phenotype in tumor specimens versus corresponding normal tissue after 2 weeks of study treatment. | Day 14 of treatment | There are two main TAM phenotypes: M1 and M2. M1 are the classically activated, anti-tumor macrophages, and M2 are the bad, pro-inflammation/neoplastic macrophages. Change in distribution will be assessed using multiparameter flow cytometry. M1 versus M2 phenotypes will be identified by utilizing macrophage-specific biomarkers. |
| Functionality of tumor-associated macrophages in tumor specimens versus corresponding normal tissue after 2 weeks of study treatment. | Day 14 of treatment | Change in functionality will be determined using efferocytosis assays. |
| Change in quantity of lipids in peripheral blood from day 0 to day 14 of study treatment. | Day 0 and Day 14 | Quantitation will be assessed using liquid chromatography tandem mass spectrometry (LC-MS/MS). This assessment will enable us to correlate peripheral blood levels of lipid mediators with tissue penetrance. For example, the investigators may find that a study treatment has a significant impact on the lipid mediator profile of the blood but that same impact is not seen in the corresponding tissue of that patient; therefore, there deductions can be made about tissue penetrance capability. |
Countries
United States
Contacts
Primary ContactAvennette Pinto
Backup ContactBeth Montera
Outcome results
None listed