Clinical trial NCT05080946: Using Aspirin to Improve Immunological Features of Ovarian Tumors
Official title: Pilot Study to Assess the Efficacy of Aspirin to Improve Immunological Features of Ovarian Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Ovarian Cancer
Fallopian Tube Cancer
Peritoneal Cancer
Lead sponsor: H. Lee Moffitt Cancer Center and Research Institute
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
name: Sharp
First posted: 2021-10-18
Enrollment: 100
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


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

Primary outcomes:
measure: Change in intratumoral density of immunosuppressive T-regulatory (FOXP3+) cells from diagnostic biopsy to interval debulking surgery
timeFrame: Up to 5 months
measure: Change in intratumoral density of M2 tumor-associated macrophages (CD163+ cells) from diagnostic biopsy to interval debulking surgery
timeFrame: Up to 5 Months
Secondary outcomes:
measure: Change in density of tumor COX1
timeFrame: Up to 5 Months
measure: Change in density of tumor COX2
timeFrame: Up to 5 Months
measure: Change in blood levels of IL-6
timeFrame: Up to 84 days
measure: Change in blood levels of p-selectin
timeFrame: Up to 84 days
measure: Change in blood levels of CA 125
timeFrame: Up to 84 days
measure: Change in tumor burden as defined by RECIST 1.1
timeFrame: Up to 5 Months
Other outcomes:
Locations:
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Charlottesville
country: United States
facility: University of Virginia Comprehensive Cancer Center
state: Virginia
city: Fairfax
country: United States
facility: Inova Schar Cancer Institute
state: Virginia
Study officials:
affiliation: Moffitt Cancer Center
name: Jing-Yi Chern, MD
role: PRINCIPAL_INVESTIGATOR
References: