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Alkylating agents

ZEN003694 + Chemotherapy for Cancer

Phase 1 & 2

Recruiting

Led By Michael Cheng

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Calculated creatinine clearance >= 60 mL/min (based on the calculated Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] glomerular filtration rate estimation for adults or 60 mL/min/1.73m^2 for patients 12-17 years as calculated based on bedside Schwartz formula

Participants must have a diagnosis of NC based on standard criteria for the disease, with diagnostic testing performed in a Clinical Laboratory Improvement Act (CLIA) certified laboratory: Ectopic expression of NUT protein per World Health Organization (WHO) criteria as determined by immunohistochemistry (IHC) testing, Detection of the NUT gene translocation as determined by fluorescence in situ hybridization (FISH) testing, Detection of the NUT gene translocation as determined by sequencing, eg. DNA next generation sequencing (NGS) or RNA sequencing.

Must not have

Pregnant women are excluded from this study because ZEN003694 is a bromodomain and extraterminal domain (BET) inhibitor with the potential for teratogenic or abortifacient effects.

Participants with known untreated central nervous system (CNS) metastases.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new combination of drugs to treat NUT carcinoma and to see if it works to shrink the tumor.

Who is the study for?

Adults and children (12-17 years) with NUT carcinoma, a rare cancer type. Participants must be able to swallow pills, have certain blood counts within normal ranges, no severe liver or kidney issues, not on specific anticoagulants or other investigational drugs, and without untreated brain metastases. They should also not have gastrointestinal disorders affecting drug absorption.

What is being tested?

The trial is testing the safety and effectiveness of adding ZEN003694 to standard chemotherapy (etoposide and cisplatin). It aims to find the best dose that's safe in phase I and then see if this combination can shrink tumors in phase II. The study will also look at changes in tumor/blood characteristics due to treatment.

What are the potential side effects?

Potential side effects include reactions related to the new drug ZEN003694 which may affect organ function similar to other anti-cancer medications. Chemotherapy with etoposide and cisplatin can cause nausea, hair loss, fatigue, increased risk of infection due to low blood cell counts.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My kidney function, measured by creatinine clearance, is good.

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My diagnosis of NUT carcinoma was confirmed by a certified lab using specific tests.

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I haven't had certain cancer treatments in the last 2 weeks or 5 half-lives, whichever is shorter.

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I am mostly active and can care for myself, regardless of my age.

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My bilirubin levels are within the normal range for my age.

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I can swallow and keep down pills.

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I had hepatitis C but am cured, or I'm being treated with an undetectable viral load.

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My hepatitis B virus is undetectable with treatment.

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My heart's electrical cycle is within a normal range.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am not pregnant, as the study drug may harm my unborn baby.

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I have brain metastases that have not been treated.

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I am not taking strong medication that affects liver enzymes.

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I cannot receive EP treatment.

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I have a history of serious heart problems.

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I have never been treated with BET inhibitors, including ZEN003694.

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I am not on blood thinners like warfarin or LMWH.

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I do not have any severe illnesses that are not under control.

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My cancer started in the chest area.

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More than a quarter of my bone marrow has been exposed to radiation.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Maximum tolerated dose (MTD) (phase 1)

Objective response rate (ORR) in patients following treatment with triplet combination (phase 2)

Secondary study objectives

Duration of response (DoR) (phase 1, phase 2, and non-thoracic, non-BRD4 exploratory cohort)

ORR (phase 1 and non-thoracic, non-BRD4 exploratory cohort)

Overall survival (phase 1, phase 2, and non-thoracic, non-BRD4 exploratory cohort)

+3 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (ZEN-3694, etoposide, cisplatin)Experimental Treatment9 Interventions

Patients receive ZEN003694 PO once or twice daily on days 1-14 or days 1-21 of each cycle depending upon dosage assignment. Patients also receive etoposide IV over 60 minutes on days 1-3 for cycles 1-4 or up to 8 cycles, and cisplatin IV over 60 minutes on day 1 of cycles 1-4 or up to 8 cycles. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may undergo radiologic evaluation (chest x-ray, CT, PET-CT, MRI, and/or FDG-PET) and biopsy throughout the study.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Magnetic Resonance Imaging

2017

Completed Phase 3

~1160

Computed Tomography

2017

Completed Phase 2

~2740