Track topics on Twitter Track topics that are important to you
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.
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)
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.
Metastatic NUT Carcinoma
Cisplatin, Etoposide, Etoposide Phosphate, Molibresib, Molibresib Besylate
Not yet recruiting
National Cancer Institute (NCI)
Published on BioPortfolio: 2019-10-10T09:39:37-0400
This phase I trial studies the side effects and best dose of molibresib and entinostat in treating patients with solid tumors or lymphomas that have spread to other parts of the body or ar...
Compassionate use access to molibresib/GSK525762 for eligible participant with NUT Midline Carcinoma; indication is a seriously debilitating or life-threatening disease.
RATIONALE: Drugs used in chemotherapy, such as cisplatin and etoposide phosphate, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them ...
This randomized phase II study compare survival outcomes and toxicity of two chemotherapy regimens (etoposide plus lobaplatin or etoposide plus cisplatin) in combination with concurrent th...
Cisplatin and Etoposide or Temozolomide and Capecitabine in Treating Patients With Neuroendocrine Carcinoma of the Gastrointestinal Tract or Pancreas That Is Metastatic or Cannot Be Removed by Surgery
This randomized phase II trial studies how well temozolomide and capecitabine work compared to standard treatment with cisplatin and etoposide in treating patients with neuroendocrine carc...
Telomeric repeat-containing RNAs (TERRAs) are long noncoding RNAs transcribed from subtelomeres toward telomeric repeat tracts, which have been implicated in telomere protection and heterochromatin fo...
Tyrosyl DNA phosphodiesterase 2 (TDP2) facilitates the repair of topoisomerase II (TOP2)-linked DNA double-strand breaks and, as a consequence, is required for cellular resistance to TOP2 "poisons". R...
The optimal therapy for advanced thymic carcinoma has long been controversial. Despite that complete (R0) resection is recommend as the first-line treatment, multidisciplinary approach including chemo...
The generic Mylan® etoposide (ETP) has been investigated as an alternative for Etopophos®, in part due to a global shortage of the latter. The generic alternative is different both in its formulatio...
Cells are daily submitted to high levels of DNA lesions that trigger complex pathways and cellular responses by cell cycle arrest, apoptosis, alterations in transcriptional response, and the onset of ...
A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle.
A pharmaceutical preparation of amlodipine besylate and olmesartan medoxomil that combines ANGIOTENSIN II TYPE I RECEPTOR ANTAGONIST and CALCIUM CHANNEL BLOCKER activities. It is used in the management of HYPERTENSION.
An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.
An enzyme of the transferase class that catalyzes the conversion of sedoheptulose 7-phosphate and D-glyceraldehyde 3-phosphate to D-ribose 5-phosphate and D-xylulose 5-phosphate in the PENTOSE PHOSPHATE PATHWAY. (Dorland, 27th ed) EC 18.104.22.168.
An enzyme of the transferase class that catalyzes the reaction sedoheptulose 7-phosphate and D-glyceraldehyde 3-phosphate to yield D-erythrose 4-phosphate and D-fructose phosphate in the PENTOSE PHOSPHATE PATHWAY. (Dorland, 27th ed) EC 22.214.171.124.
In a clinical trial or interventional study, participants receive specific interventions according to the research plan or protocol created by the investigators. These interventions may be medical products, such as drugs or devices; procedures; or change...
Bladder Cancer Brain Cancer Breast Cancer Cancer Cervical Cancer Colorectal Head & Neck Cancers Hodgkin Lymphoma Leukemia Lung Cancer Melanoma Myeloma Ovarian Cancer Pancreatic Cancer ...
Surgery is a technology consisting of a physical intervention on tissues. All forms of surgery are considered invasive procedures; so-called "noninvasive surgery" usually refers to an excision that does not penetrate the structure being exci...