Zafirlukast in Treatment of Marker Relapsed Ovarian Cancer
Zafirlukast in Treatment of Marker Relapsed Ovarian Cancer
This research study is evaluating the effectiveness of Zafirlukast to prevent tumor activity
 in participants with tumor marker-only relapsed ovarian cancer.

 -  The name of the study drug involved in this study is:

 -  Zafirlukast
This is a single-arm Simon two-stage phase 2 clinical trial to determine whether zafirlukast
 reduces the tumor marker CA-125 as well the tendency to form blood clots in tumor marker-only
 relapsed ovarian cancer.

 The research study procedures include screening for eligibility and study treatment including
 evaluations and follow up visits.

 -  The name of the study drug involved in this study is:

 -  Zafirlukast

 Eligible participants will receive study treatment for up to 1 year and will be followed for
 up to one year following treatment.

 It is expected that about 30 people will take part in this research study.

 The U.S. Food and Drug Administration (FDA) has not approved zafirlukast for this specific
 disease but it has been approved for other uses.

 Zafirlukast is currently approved to be used for the treatment of asthma. It has been
 recently learned that Zakfirlukast demonstrates anti-tumor activity in laboratory studies of
 ovarian cancer. This means that these results were not found in humans.

 The National Institutes of Health are supporting this research study by providing funding
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 and
 surgery with a response, in the opinion of the investigator, defined as no evidence of
 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-125 more
 than twice the upper limit of normal (35 U/mL) in the setting of a normal baseline
 CA-125 levels or CA-125 greater than twice the nadir count on two successive
 measurements for CA-125 values that remain above baseline without measurable
 radiographic disease.

 -  Minimum age ≥ 18 years. Because no dosing or adverse event data are currently
 available on the use of zafirlukast in participants under 18 years of age with ovarian
 cancer, children are excluded from this study but will be eligible for future
 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 incompletely
 characterized. For this reason, women of child-bearing potential must agree to use
 adequate contraception (hormonal or barrier method of birth control; abstinence) prior
 to study entry and for the duration of study participation. Should a woman become
 pregnant or suspect she is pregnant while she or her partner is participating in this
 study, she should inform her treating physician immediately. Men are not eligible for
 this study.

 -  Ability to understand and the willingness to sign a written informed consent document

 Exclusion Criteria:

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

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

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

 -  Participants who are receiving any other investigational agents.

 -  Participants with known brain metastases should be excluded from this clinical trial
 because of their poor prognosis and because they often develop progressive neurologic
 dysfunction that would confound the evaluation of neurologic and other adverse events.

 -  History of allergic reactions attributed to compounds of similar chemical or biologic
 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 use
 regular use of higher doses of non-steroidal anti-inflammatory agents as determined by
 the treating physician (e.g. ibuprofen > 800 mg daily or equivalent).

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

 -  Participants with uncontrolled intercurrent illness.

 -  Participants with psychiatric illness/social situations that would limit compliance
 with study requirements.

 -  Pregnant women are excluded from this study because zafirlukast is a class B agent
 with the potential for teratogenic or abortifacient effects. Because there is an
 unknown but potential risk for adverse events in nursing infants secondary to
 treatment of the mother with zafirlukast, breastfeeding should be discontinued if the
 mother is treated with zafirlukast.