Zafirlukast in Treatment of Marker Relapsed Ovarian Cancer

A Phase 2 Study of Zafirlukast for the Treatment of Tumor-marker Only 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

Study Overview

• Status: Recruiting
• Conditions: Ovarian Cancer
• Intervention / Treatment: Drug: 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

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Rushad Patell, MD; Phone Number: 617-667-2139; Email: rpatell@bidmc.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Beth Israel Deaconess Medical Center
      • Contact: Rushad Patell, MD; Phone Number: 617-667-2139; Email: rpatell@bidmc.harvard.edu
      • Principal Investigator: Rushad Patell, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Zafirlukast; Zafirlukast will be taken orally at a pre-determined dose 2x daily for 28 day cycle up to 1 year.	Drug: Zafirlukast; Oral tablets, 2x daily for 28 day cycle up to 1 year; Other Names: Accolate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	84 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma D-Dimer Response Rate	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.	baseline to 28 days

Collaborators and Investigators

• Sponsor: Beth Israel Deaconess Medical Center
• Collaborators: National Cancer Institute (NCI); Dana-Farber Cancer Institute; National Institutes of Health (NIH)
• Investigators: Principal Investigator: Rushad Patell, MD, Beth Israel Deaconess Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): June 24, 2020
• Primary Completion (Estimated): December 31, 2023
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: April 6, 2020
• First Submitted That Met QC Criteria: April 6, 2020
• First Posted (Actual): April 9, 2020

Study Record Updates

• Last Update Posted (Actual): June 15, 2023
• Last Update Submitted That Met QC Criteria: June 14, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Ovarian Cancer; Relapsed Ovarian Cancer
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Asthmatic Agents; Respiratory System Agents; Leukotriene Antagonists; Hormone Antagonists; Zafirlukast
• Other Study ID Numbers: 19-814; 1R21CA231000-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
• IPD Sharing Time Frame: Data can be shared no earlier than 1 year following the date of publication
• IPD Sharing Access Criteria: Contact the Beth Israel Deaconess Medical Center Technology Ventures Office at tvo@bidmc.harvard.edu
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No