Clinical Trials /

Zafirlukast in Treatment of Marker Relapsed Ovarian Cancer

NCT04339140

Description:

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

Related Conditions:
  • Fallopian Tube Carcinoma
  • Ovarian Carcinoma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Zafirlukast in Treatment of Marker Relapsed Ovarian Cancer
  • Official Title: A Phase 2 Study of Zafirlukast for the Treatment of Tumor-marker Only Relapsed Ovarian Cancer

Clinical Trial IDs

  • ORG STUDY ID: 19-814
  • NCT ID: NCT04339140

Conditions

  • Ovarian Cancer
  • Relapsed Ovarian Cancer
  • Biological Tumor Markers

Interventions

DrugSynonymsArms
ZafirlukastAccolateZafirlukast

Purpose

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
    

Trial Arms

NameTypeDescriptionInterventions
ZafirlukastExperimentalZafirlukast will be taken orally at a pre-determined dose 2x daily for 28 day cycle up to 1 year.
  • Zafirlukast

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:CA-125 Response Rate
Time Frame:84 days
Safety Issue:
Description: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

Secondary Outcome Measures

Measure:Plasma D-Dimer Response Rate
Time Frame:baseline to 28 days
Safety Issue:
Description:Plasma D-dimer response will be calculated as a proportion of those patients with a decrease in D-dimer of > 20% relative to baseline. Statistical differences will be analyzed using a paired t-test comparing baseline and C2D1 values.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Dana-Farber Cancer Institute

Trial Keywords

  • Ovarian Cancer
  • Relapsed Ovarian Cancer
  • Biological Tumor Markers

Last Updated

April 6, 2020