Metastatic NUT Carcinoma Clinical Trial
Official title:
A Phase 1/2 Study of the Bromodomain Inhibitor Molibresib in Combination With Etoposide/Platinum in Patients With NUT Carcinoma
This phase I/II trial studies the side effects and best dose of molibresib when given together with chemotherapy (etoposide and cisplatin) and how well they work for the treatment of NUT cancer that has spread to other places in the body (metastatic) or cannot be removed by surgery (unresectable). Molibresib may stop the growth of tumor cells by blocking some of the proteins needed for cell growth. Drugs used in chemotherapy, such as etoposide and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Adding molibresib to chemotherapy (etoposide and cisplatin), may work better in treating patients with NUT cancer compared to the usual approach.
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of the
combination of molibresib besylate (molibresib [GSK525762C]) with etoposide phosphate
(etoposide) and cisplatin (EP) in patients with NUT carcinoma (NC). (Phase I) II. Evaluate
the overall objective response rate (ORR) of the triplet combination in participants
utilizing Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria. (Phase
II)
SECONDARY OBJECTIVES:
I. Evaluate the preliminary progression-free survival (PFS) rate, ORR, duration of response
(DoR), and overall survival (OS) rate of the triplet combination in participants utilizing
RECIST version 1.1 criteria. (Phase I) II. Determine the pharmacokinetic (PK) profile of the
triplet combination. (Phase I) III. Determine the PFS, DoR, and OS rates of the triplet in
participants with NC using RECIST version 1.1 criteria. (Phase II) IV. Confirm the safety and
tolerability of the regimen in this patient population. (Phase II) V. Evaluate the
preliminary PFS rate, ORR, DoR, and the OS rate of GSK525762C monotherapy in a small
exploratory cohort of patients with non-thoracic origin, non-BRD4-NUT NC. (Phase II) VI. To
observe and record anti-tumor activity. (Phase 1, phase 2, and non-thoracic, non-BRD4
exploratory cohort) VII. Explore potential biomarker indicators of response and resistance in
tumor tissue samples. (Phase 1, phase 2, and non-thoracic, non-BRD4 exploratory cohort)
VIII. 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:
VIIIa. Identify potential predictive and prognostic biomarkers beyond any genomic alteration
by which treatment may be assigned. (Phase 1, phase 2, and non-thoracic, non-BRD4 exploratory
cohort) VIIIb. Identify resistance mechanisms using genomic deoxyribonucleic acid (DNA)- and
RNA-based assessment platforms. (Phase 1, phase 2, and non-thoracic, non-BRD4 exploratory
cohort) IX. 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. (Phase 1, phase 2, and non-thoracic, non-BRD4 exploratory
cohort) X. To bank formalin-fixed, paraffin-embedded (FFPE) tissue, blood (for cell-free DNA
analysis), and nucleic acids obtained from patients at the Experimental Therapeutics Clinical
Trials Network (ETCTN) Biorepository at Nationwide Children's Hospital. (Phase 1, phase 2,
and non-thoracic, non-BRD4 exploratory cohort)
OUTLINE: This is a phase I, dose-escalation study of molibresib besylate followed by a phase
II study. Patients are assigned to 1 of 2 cohorts.
PHASE I AND II COHORT: Patients receive molibresib besylate orally (PO) once daily (QD) on
days 1-14 (may switch to days 1-21 after completion of etoposide and cisplatin cycles).
Patients also receive etoposide phosphate intravenously (IV) over 60 minutes on days 1-3 and
cisplatin IV over 60 minutes on day 1 of cycles 1-4. Treatments repeat every 21 days in the
absence of disease progression or unacceptable toxicity. After completion of cycle 4,
patients may receive etoposide phosphate and cisplatin for up to 8 cycles total in the
absence of disease progression or unacceptable toxicity at the investigator's discretion.
Non-BRD4 EXPLORATORY COHORT: Patients receive molibresib besylate PO QD on days 1-21. Cycles
repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients
who experience disease progression may receive molibresib besylate, etoposide phosphate and
cisplatin as in Phase I and II Cohort at the discretion of the principal investigator.
After completion of study treatment, patients are followed up for 30 days and then every 4
weeks for up to 2 years.
;
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Recruiting |
NCT05019716 -
Testing the Safety and Efficacy of the Addition of A New Anti-cancer Drug, ZEN003694, to Chemotherapy Treatment (Etoposide and Cisplatin) for Adult and Pediatric Patients (12-17 Years) With NUT Carcinoma
|
Phase 1/Phase 2 |