Using Aspirin to Improve Immunological Features of Ovarian Tumors

Study Overview
=================
Brief Summary
-----------------
The purpose of the study is to evaluate the effectiveness of aspirin with neoadjuvant chemotherapy for decreasing markers of immune suppression in the tumor at interval debulking surgery, in women with diagnosed ovarian, fallopian tube, or peritoneal carcinoma

Official Title
-----------------
Pilot Study to Assess the Efficacy of Aspirin to Improve Immunological Features of Ovarian Tumors

Conditions
-----------------
Ovarian Cancer, Fallopian Tube Cancer, Peritoneal Cancer

Intervention / Treatment
-----------------
* Drug: Aspirin 325mg
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participants that are greater than or equal to 18 years of age For U.S. sites, patients can read and understand English or Spanish; for Canadian site, participants can read and understand English or French Histology confirmed, or clinical suspicion of, invasive epithelial ovarian, fallopian tube, or peritoneal carcinoma. Must be grade 2 or 3 or high (where high is defined as grade 2/3). All histologies including serous, endometrioid, clear cell sarcoma, or carcinosarcoma histology is acceptable. Mixed histology also acceptable. Treatment naïve for this cancer diagnosis Planned for neoadjuvant chemotherapy (platinum-based doublet with taxane +/- anti-VEGF antibody) for at least 3 but no more than 5 cycles followed by an interval debulking surgery. [Note: this study evaluates response while on neoadjuvant treatment. The final collection of specimen and questionnaire is at the time of surgery and immediate post-operative state. Therefore, there are no eligibility criteria related to treatment in the adjuvant setting (e.g., intraperitoneal treatment) and adjuvant therapy should proceed as the physician deems appropriate.] Measurable disease as defined by RECIST 1.1, CT scan (with or without contrast) within 12 weeks of study enrollment. Eastern Cooperative Oncology Group (ECOG) performance status of 0,1, or 2 Able to provide tissue biopsy (core or excisional) sufficient for diagnosis and biomarker analysis, may use outside archival tissue if available. If currently using anti-coagulation medication, no contraindication for temporary stoppage of use during the study based on physician judgement Willing and able to swallow pills without difficulty Un-transfused platelet count > 100,000 cells/μL Willing and able to participate in all required evaluations and procedures in this study protocol (e.g. undergoing treatment, scheduled visits and examinations, serum testing, questionnaires, pill log/diary) Absolute neutrophil count > 1.5 x 109 cells/L Hemoglobin > 9.0 g/dL, may use transfusions and the value can be post-transfusion Estimated creatinine clearance of > 30 mL/min, calculated using the formula Cockcroft-Gault [(140-age) x Mass (kg)/(72 x creatinine mg/dL)] x 0.85 for female No severe hepatic impairment defined as AST or ALT elevation < 2.5 x institutional ULN, unless liver metastasis is present < 5 x ULN Exclusion Criteria: Definite contraindication for either aspirin use or stopping current aspirin use based on physician's clinical judgment History of vascular event in the last 12 months (e.g., myocardial infarction or unstable angina, stroke, coronary artery angioplasty or stenting, coronary artery bypass graft, relevant [serious or significant] arrhythmias, significant vascular disease, congestive heart failure or vascular interventions). History of hypertensive crisis and/ or uncontrolled HTN, systolic blood pressure > 150 mmHg; diastolic blood pressure > 90mmHg. Participants must have blood pressure < 150/90 mmHg taken in a clinic setting by a medical professional within 2 weeks prior to starting study. Current or history of ulcers which prohibits aspirin consumption, severe hepatic failure, or acute or chronic renal disease where aspirin use is contraindicated History of gastrointestinal or genitourinary bleeding or other bleeding diathesis or coagulopathy within 6 months prior to enrollment of study Uncontrolled erosive esophagitis requiring 2 or more treatments Other cancer diagnosis in the last 3 years other than non-melanoma skin cancer Autoimmune disorder requiring systemic therapy Chronic steroid use defined as 3 weeks in the past year or any length of time in the past 30 days. Other aspirin or NSAID hypersensitivities or contraindications (e.g. allergy) History of bariatric surgery Currently pregnant at the Screening visit or planning on becoming pregnant during the study period Participant is unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with study medication. Metabolism CYP2C9, known G6PD deficient patients

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Participants Randomized to Aspirin<br>Participants randomized to this arm will receive 325mg daily dose aspirin | Drug: Aspirin 325mg<br>* Participants will receive a tablet of 325mg aspirin that is taken once daily by mouth. Study treatment begins on first day of neoadjuvant chemotherapy for up to 5 cycles. Participants will be expected to take the study treatment for between 63 and 175 days (3-5 cycles). Participants will stop taking study treatment 7 days prior to participants interval debulking surgery.<br>|
| Placebo Comparator: Participants Randomized to Placebo<br>Participants randomized to this arm will receive a daily dose of a placebo (inactive substance) | Drug: Placebo<br>* Participants will receive a placebo tablet that is taken once daily by mouth. Study treatment begins on first day of neoadjuvant chemotherapy for up to 5 cycles. Participants will be expected to take the study treatment for between 63 and 175 days (3-5 cycles). Participants will stop taking study treatment 7 days prior to participants interval debulking surgery.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in intratumoral density of immunosuppressive T-regulatory (FOXP3+) cells from diagnostic biopsy to interval debulking surgery | Change in intratumoral density of immunosuppressive T-regulatory (FOXP3+) cells will be measured by using this formula: (density in the debulking surgery tissue sample - density in the biopsy tissue sample)*100 / density in the biopsy tissue sample. | Up to 5 months | 
| Change in intratumoral density of M2 tumor-associated macrophages (CD163+ cells) from diagnostic biopsy to interval debulking surgery | Change in intratumoral density of of M2 tumor-associated macrophages (CD163+ cells) will be measured by using this formula: (density in the debulking surgery tissue sample - density in the biopsy tissue sample)*100 / density in the biopsy tissue sample. | Up to 5 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in density of tumor COX1 | Change in density of tumor COX1 will be measured by using this formula: (density in the debulking surgery tissue sample - density in the biopsy tissue sample)*100 / density in the biopsy tissue sample. | Up to 5 Months | 
| Change in density of tumor COX2 | Change in density of tumor COX2 will be measured by using this formula: (density in the debulking surgery tissue sample - density in the biopsy tissue sample)*100 / density in the biopsy tissue sample. | Up to 5 Months | 
| Change in blood levels of IL-6 | Investigators will calculate the percent change in the concentration of the biomarker from baseline to Visit 4 | Up to 84 days | 
| Change in blood levels of p-selectin | Investigators will calculate the percent change in the concentration of the biomarker from baseline to Visit 4 | Up to 84 days | 
| Change in blood levels of CA 125 | Investigators will calculate the percent change in the concentration of the biomarker from baseline to Visit 4 | Up to 84 days | 
| Change in tumor burden as defined by RECIST 1.1 | Change in tumor burden be assessed using Response Evaluation Criteria in Solid Tumors guideline version 1.1 (RECIST 1.1) | Up to 5 Months |