Zafirlukast in Treatment of Marker Relapsed Ovarian Cancer

Inclusion Criteria:

• Participants must have histologically confirmed epithelial ovarian, fallopian tube,or primary peritoneal cancer.

• Participants must have completed at least first-line platinum based chemotherapy andsurgery with a response, in the opinion of the investigator, defined as no evidenceof disease progression or rising CA-125 at any time during front-line treatment.

• Participants must meet criteria for tumor marker-only relapse, defined as CA-125more than twice the upper limit of normal (35 U/mL) in the setting of a normalbaseline CA-125 levels or CA-125 greater than twice the nadir count on twosuccessive measurements for CA-125 values that remain above baseline withoutmeasurable radiographic disease.

• Minimum age ≥ 18 years. Because no dosing or adverse event data are currentlyavailable on the use of zafirlukast in participants under 18 years of age withovarian cancer, children are excluded from this study but will be eligible forfuture pediatric trials.

• Life expectancy of greater than 4 months.

• ECOG performance status ≤ 2 (Karnofsky ≥ 60%, see Appendix A).

• Participants must be able to swallow tablets.

• Participants must have adequate organ and marrow function as defined below:

• Absolute neutrophil count ≥1,000/mcL

• Platelets ≥100,000/mcL

• Total bilirubin ≤ 1.3 × institutional upper limit of normal (ULN)

• AST(SGOT)/ALT(SGPT) ≤ 2 × institutional ULN

• Creatinine ≤ institutional ULN OR

• Glomerular filtration rate (GFR) ≥45 mL/min/1.73 m2

• The effects of zafirlukast on the developing human fetus are incompletelycharacterized. For this reason, women of child-bearing potential must agree to useadequate contraception (hormonal or barrier method of birth control; abstinence)prior to study entry and for the duration of study participation. Should a womanbecome pregnant or suspect she is pregnant while she or her partner is participatingin this study, she should inform her treating physician immediately. Men are noteligible for this study.

• Ability to understand and the willingness to sign a written informed consentdocument

Exclusion Criteria:

• Non-epithelial tumors (pure sarcomas) or ovarian tumors with low malignant potential (ie borderline tumors) or mucinous tumors. Mixed mullerian tumors or carcinosarcomasare allowed.

• Participants who have had cytotoxic chemotherapy including bevacizumab orradiotherapy within 4 weeks prior to entering the study. This does not includemaintenance therapy (>8 weeks prior to enrollment of stable dose) with a PARPinhibitor, such as olaparib or niraparib. (PARP inhibitor, rucaparib is not allowedto be co-administered with CYP2C9 substrates as maintenance therapy as it couldincrease exposure to zafirlukast).

• Participants who have ongoing adverse effects from prior anti-cancer therapy greaterthan National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, v5.0) Grade 1, with the exception of Grade 2 non-hematologic toxicity suchas alopecia and peripheral neuropathy.

• Participants who are receiving any other investigational agents.

• Participants with known brain metastases should be excluded from this clinical trialbecause of their poor prognosis and because they often develop progressiveneurologic dysfunction that would confound the evaluation of neurologic and otheradverse events.

• History of allergic reactions attributed to compounds of similar chemical orbiologic composition to zafirlukast.

• Currently receiving anticoagulant therapy.

• Current daily use of aspirin (> 81 mg daily), clopidogrel (Plavix), cilostazol (Pletal), aspirin-dipyridamole (Aggrenox) (within 10 days) or considered to useregular use of higher doses of non-steroidal anti-inflammatory agents as determinedby the treating physician (e.g. ibuprofen > 800 mg daily or equivalent).

• Participants receiving any medications or substances that are inhibitors or inducersof CYP2C9 are ineligible. Because the lists of these agents are constantly changing,it is important to regularly consult a frequently updated medical reference. As partof the enrollment/informed consent procedures, the participant will be counseled onthe risk of interactions with other agents, and what to do if new medications needto be prescribed or if the participant is considering a new over-the-countermedicine or herbal product.

• Participants with uncontrolled intercurrent illness.

• Participants with psychiatric illness/social situations that would limit compliancewith study requirements.

• Pregnant women are excluded from this study because zafirlukast is a class B agentwith the potential for teratogenic or abortifacient effects. Because there is anunknown but potential risk for adverse events in nursing infants secondary totreatment of the mother with zafirlukast, breastfeeding should be discontinued ifthe mother is treated with zafirlukast.