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RecruitingNCT05019716

Testing the Safety and Efficacy of the Addition of a New Anti-cancer Drug, ZEN003694, to Chemotherapy Treatment (Cisplatin and Etoposide or Carboplatin and Paclitaxel) for Adult and Pediatric Patients (12-17 Years) With NUT Carcinoma

A Phase 1 Study of the Bromodomain Inhibitor ZEN003694 in Combination With Platinum-based Chemotherapy in Patients With NUT Carcinoma

Status
Recruiting
Phase
Phase 1 / Phase 2
Study type
Interventional
Enrollment
36 (estimated)
Sponsor
National Cancer Institute (NCI) · NIH
Sex
All
Age
12 Years
Healthy volunteers
Not accepted

Summary

This phase I trial tests the safety, side effects, and best dose of ZEN003694 in combination with cisplatin and etoposide or carboplatin and paclitaxel in treating patients with NUT carcinoma. Another purpose of this study is to see whether there are any changes in patient's tumor or blood characteristics (e.g. genes, molecules, etc.) due to combination therapy. ZEN003694 inhibits the production of certain growth-promoting proteins and may prevent proliferation of tumor cells that use those proteins for their growth. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of tumor cells. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and deoxyribonucleic acid (DNA) repair and may kill tumor cells. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Paclitaxel is in a class of medications called antimicrotubule agents. It stops tumor cells from growing and dividing and may kill them. Combination therapy with ZEN003694 and etoposide and cisplatin or carboplatin and paclitaxel may be safe and effective in treating patients with NUT carcinoma.

Detailed description

PRIMARY OBJECTIVE: I. Determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of the addition of BET bromodomain inhibitor ZEN-3694 (ZEN003694) to etoposide and cisplatin (EP) in participants with NUT carcinoma (NC). SECONDARY OBJECTIVES: I. Evaluate the preliminary progression-free survival (PFS) rate, overall response rate (ORR), duration of response (DoR), and overall survival (OS) of the addition of ZEN003694 to etoposide and cisplatin (EP) in participants with NC utilizing Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria. II. Determine the pharmacokinetic (PK) profile of ZEN003694, etoposide, and cisplatin when administered in combination. III. To observe and record anti-tumor activity. (Phase 1, non-thoracic, non-BRD4 exploratory cohort, and ZEN003694/carboplatin/paclitaxel safety cohort) IV. Explore potential biomarker indicators of response and resistance in tumor tissue samples. (Phase 1, non-thoracic, non-BRD4 exploratory cohort, and ZEN003694/carboplatin/paclitaxel safety cohort) V. To perform molecular profiling assays on malignant and normal tissues, including, but not limited to, whole exome sequencing (WES) and messenger ribonucleic acid (RNA) sequencing (RNAseq), in order to: Va. Identify potential predictive and prognostic biomarkers beyond any genomic alteration by which treatment may be assigned; (Phase 1, non-thoracic, non-BRD4 exploratory cohort, and ZEN003694/carboplatin/paclitaxel safety cohort) Vb. Identify resistance mechanisms using genomic DNA- and RNA-based assessment platforms; (Phase 1, non-thoracic, non-BRD4 exploratory cohort, and ZEN003694/carboplatin/paclitaxel safety cohort) VI. To contribute genetic analysis data from de-identified biospecimens to Genomic Data Commons (GDC), a well annotated cancer molecular and clinical data repository, for current and future research; specimens will be annotated with key clinical data, including presentation, diagnosis, staging, summary treatment, and if possible, outcome. (Phase 1, non-thoracic, non-BRD4 exploratory cohort, and ZEN003694/carboplatin/paclitaxel safety cohort) VII. To bank formalin-fixed, paraffin-embedded (FFPE) tissue, blood (for cell-free DNA analysis), and nucleic acids obtained from patients at the National Cancer Institute (NCI) Early-Phase and Experimental Clinical Trials Biospecimen Bank (EET Biobank) at Nationwide Children's Hospital. (Phase 1, non-thoracic, non-BRD4 exploratory cohort, and ZEN003694/carboplatin/paclitaxel safety cohort) VIII. Evaluate the safety and tolerability of ZEN003694 in combination with carboplatin and paclitaxel in participants with NC. (ZEN003694/carboplatin/paclitaxel safety cohort) IX. To determine the PK profile of the combination of ZEN003694, carboplatin, and paclitaxel in combination. (ZEN003694/carboplatin/paclitaxel safety cohort) OUTLINE: This is a dose escalation study of ZEN003694 with fixed dose etoposide and cisplatin OR fixed dose carboplatin and paclitaxel. Patients are assigned to 1 of 3 cohorts. COHORT I (PHASE 1): Patients receive ZEN003694 orally (PO) once or twice daily on days 1-14 or days 1-21 of each cycle depending upon dosage assignment. Patients also receive etoposide intravenously (IV) over 60 minutes on days 1-3 of each cycle and cisplatin IV over 60 minutes on day 1 of each cycle. Cycles repeat every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients may then receive etoposide and cisplatin for an additional 4 cycles in the absence of disease progression or unacceptable toxicity, per the treating investigator's discretion. After completion of etoposide and cisplatin treatment, patients may then receive ZEN003694 PO once or twice daily on days 1-14 or 1-21 of each cycle, per the treating investigator's discretion. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo imaging scans, blood sample collection, and biopsies throughout the study. COHORT II (SAFETY COHORT): 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 carboplatin IV over 15-30 minutes on day 1 of each cycle and paclitaxel IV over 3 hours on day 1 of each cycle. Cycles repeat every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients may then receive carboplatin and paclitaxel for an additional 4 cycles in the absence of disease progression or unacceptable toxicity, per the treating investigator's discretion. After completion of carboplatin and paclitaxel treatment, patients may then receive ZEN003694 PO once or twice daily on days 1-14 or 1-21 of each cycle, per the treating investigator's discretion. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo imaging scans, blood sample collection, and biopsies throughout the study. COHORT III (NON-THORACIC, NON-BRD4 EXPLORATORY COHORT): Patients receive ZEN003694 PO on days 1-5, 8-12, and 15-19 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression have the option to cross-over to Cohort I and receive treatment for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Cross-over patients may then receive ZEN003694 PO on days 1-21 of each cycle in the absence of disease progression or unacceptable toxicity, per the treating investigator's discretion. Patients also undergo imaging scans, blood sample collection, and biopsies throughout the study. After completion of study treatment, patients are followed for 30 days after the last dose and then every 4 weeks for a maximum of 2 years.

Conditions

Interventions

TypeNameDescription
DRUGBET Bromodomain Inhibitor ZEN-3694Given PO
PROCEDUREBiopsy ProcedureUndergo biopsy
PROCEDUREBiospecimen CollectionUndergo blood sample collection
DRUGCarboplatinGiven IV
DRUGCisplatinGiven IV
DRUGEtoposideGiven IV
PROCEDUREImaging ProcedureUndergo imaging scans
DRUGPaclitaxelGiven IV

Timeline

Start date
2022-07-13
Primary completion
2026-06-30
Completion
2026-06-30
First posted
2021-08-25
Last updated
2026-04-13

Locations

5 sites across 1 country: United States

Regulatory

Source: ClinicalTrials.gov record NCT05019716. Inclusion in this directory is not an endorsement.