Ovarian Cancer
Conditions
Keywords
Ovarian Cancer, Relapsed Ovarian Cancer
Brief summary
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
Detailed description
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
Interventions
DRUGZafirlukast
Oral tablets, 2x daily for 28 day cycle up to 1 year
Sponsors
National Institutes of Health (NIH)
National Cancer Institute (NCI)
Dana-Farber Cancer Institute
Beth Israel Deaconess Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| CA-125 Response Rate | 84 days | Response will be defined according to GCIG criteria which requires a reduction of CA-125 of \> 50% relative to pre-treatment CA-125 level, maintained for at least 28 days |
Countries
United States
Participant flow
Recruitment details
Single-arm study. All participants received 40 mg of Zafirlukast twice daily.
Participants by arm
| Arm | Count |
|---|---|
| Zafirlukast Zafirlukast will be taken orally at a pre-determined dose 2x daily for 28 day cycle up to 1 year.
Zafirlukast: Oral tablets, 2x daily for 28 day cycle up to 1 year | 4 |
| Total | 4 |
Baseline characteristics
| Characteristic | Zafirlukast |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 4 |
| other Total, other adverse events | 3 / 4 |
| serious Total, serious adverse events | 0 / 4 |
Outcome results
Primary
CA-125 Response Rate
Response will be defined according to GCIG criteria which requires a reduction of CA-125 of \> 50% relative to pre-treatment CA-125 level, maintained for at least 28 days
Time frame: 84 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Zafirlukast | CA-125 Response Rate | 0 Participants |