Neoplasms

All Conditions

Digestive System Diseases

Gland and Hormone Related Diseases

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Carcinoma

Pancreatic Neoplasms

Lymphoma

Lymphoma, T-Cell

Lymphoma, B-Cell

Lymphoma, Non-Hodgkin

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Neoplasms, Glandular and Epithelial

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

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Endocrine System Diseases

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B-cell Lymphoma

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Antineoplastic Agents

All Drugs and Chemicals

Entinostat

Histone Deacetylase Inhibitors

Enzyme Inhibitors

Patients receive entinostat PO on days 1, 8, 15, and 22 and molibresib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Molibresib

Patricia M LoRusso

This phase I trial studies the side effects and best dose of GSK525762C (molibresib besylate) and entinostat in treating patients with solid tumors or lymphomas that have spread to other parts of the body (advanced) or are not responding to treatment (refractory). GSK525762C and entinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. This study may help doctors find out if giving the combination of GSK525762C and entinostat is better or worse than the usual approach for treating solid tumors or lymphomas.

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of GSK525762C and entinostat in combination in patients with advanced and refractory solid tumors and lymphomas based on dose limiting toxicities (DLTs) of the combination of GSK525762C and entinostat.

SECONDARY OBJECTIVES:

I. To describe the safety profile of GSK525762C and entinostat in advanced and refractory solid tumors and lymphomas.

II. To determine the overall response rate (ORR) of GSK525762C and entinostat in advanced and refractory solid tumors and lymphomas.

III. To determine the progression-free survival (PFS), duration of response (DOR), and overall survival (OS) of GSK525762C and entinostat in this patient population.

EXPLORATORY OBJECTIVES:

I. To assess the effect of GSK525762C and entinostat therapy on apoptosis, as measured by an apoptosis multiplex immunoassay.

II. To assess the effect of GSK525762C and entinostat therapy on c-MYC and YAP1 as measured by ribonucleic acid (RNA) and protein expression.

III. To assess the effect of GSK525762C and entinostat therapy on tumor burden and gene expression patterns as measured by whole exome sequencing (WES) and RNA sequencing (RNASeq) on circulating tumor deoxyribonucleic acid (DNA) (ctDNA) specimens.

OUTLINE: This is a dose-escalation study.

Patients receive entinostat orally (PO) on days 1, 8, 15, and 22, and molibresib PO once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 4 weeks.

Testing a New Anti-cancer Drug Combination, Entinostat and GSK525762C, for Advanced and Refractory Solid Tumors and Lymphomas

Phase I Study of GSK525762C and Entinostat in Advanced and Refractory Solid Tumors and Lymphomas

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Measured by an apoptosis multiplex immunoassay. Statistical and bioinformatic data analysis for laboratory non-omics data and clinical data will utilize the following general strategies, as appropriate. For single time-point lab data, tests of hypotheses concerning within-group comparisons will be completed using the paired t-test or Wilcoxon signed-rank test for continuous parameters of interest, or McNemar's Chi-square test for categorical parameters of interest. Between-group comparisons will be assessed using either analysis of variance (ANOVA) with adjusted least squares means or Fisher's exact test, for continuous or categorical variables of interest, respectively. For count or binary multiple time-points or correlated data, tests of between-group comparisons will be completed using the generalized estimating equation (GEE) statistical procedure for longitudinal data analysis with multiple observable vectors for the same subject.

Measured by ribonucleic acid (RNA) and protein expression. Statistical and bioinformatic data analysis for laboratory non-omics data and clinical data will utilize the following general strategies, as appropriate. For single time-point lab data, tests of hypotheses concerning within-group comparisons will be completed using the paired t-test or Wilcoxon signed-rank test for continuous parameters of interest, or McNemar's Chi-square test for categorical parameters of interest. Between-group comparisons will be assessed using either ANOVA with adjusted least squares means or Fisher's exact test, for continuous or categorical variables of interest, respectively. For count or binary multiple time-points or correlated data, tests of between-group comparisons will be completed using the GEE statistical procedure for longitudinal data analysis with multiple observable vectors for the same subject.

Measured by RNA and protein expression. Statistical and bioinformatic data analysis for laboratory non-omics data and clinical data will utilize the following general strategies, as appropriate. For single time-point lab data, tests of hypotheses concerning within-group comparisons will be completed using the paired t-test or Wilcoxon signed-rank test for continuous parameters of interest, or McNemar's Chi-square test for categorical parameters of interest. Between-group comparisons will be assessed using either ANOVA with adjusted least squares means or Fisher's exact test, for continuous or categorical variables of interest, respectively. For count or binary multiple time-points or correlated data, tests of between-group comparisons will be completed using the GEE statistical procedure for longitudinal data analysis with multiple observable vectors for the same subject.

As measured by whole exome sequencing and RNA sequencing (RNASeq) on circulating tumor deoxyribonucleic acid (DNA) specimens.

As measured by whole exome sequencing and RNASeq on circulating tumor DNA specimens.

Assesses with dose limiting toxicities. Descriptive statistics, including means, standard deviations, and ranges for continuous parameters, as well as percentages and frequencies for categorical parameters, will be presented.

Graded per Common Terminology Criteria for Adverse Events version 5.0. National Cancer Institute toxicity grade 3 and grade 4 laboratory abnormalities will be listed.

The exact two-sided 95% confidence intervals (CIs) for the RR will be reported.

Will be estimated using the Kaplan-Meier method with the 95% CIs. The CI based on Greenwood's variance will be reported. In addition, the possible risk factors will be compared for survival with log-rank test.

The 95% CIs for the duration of response will be reported.

National Cancer Institute (NCI)

molibresib 20 mg will be supplied for compassionate use for the identified individual subject.

molibresib

GSK Clinical Trials

Compassionate use access to molibresib/GSK525762 for eligible participant with NUT Midline Carcinoma; indication is a seriously debilitating or life-threatening disease.

Investigational Product GSK525762 is an orally bioavailable small molecule that is a potent inhibitor of the binding of BET proteins to acetylated histones. Binding of GSK525762 induces squamous differentiation and inhibits proliferation of patient-derived NMC cell lines both in culture and in murine xenografts.

Compassionate use access to molibresib is restricted to patients with confirmed diagnosis of NUT Midline Carcinoma.

Compassionate Use Individual Request Program for GSK525762 in NUT Midline Carcinoma

GlaxoSmithKline

Dermatologic Agents

Etoposide

Cisplatin

Etoposide phosphate

Podophyllotoxin

Keratolytic Agents

Tubulin Modulators

Antimitotic Agents

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.

Patients receive molibresib besylate PO QD on days 1-14 (may switch to days 1-21 after completion of etoposide and cisplatin cycles). Patients also receive etoposide phosphate 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.

Etoposide Phosphate

Molibresib Besylate

Geoffrey I Shapiro

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.

Testing of the Addition of a New Anti-cancer Drug, Molibresib, to Chemotherapy Treatment (Etoposide and Cisplatin) for Patients With NUT Carcinoma

A Phase 1/2 Study of the Bromodomain Inhibitor Molibresib in Combination With Etoposide/Platinum in Patients With NUT Carcinoma

Assessed using Common Terminology Criteria for Adverse Events (CTCAE) version (V.) 5.0 criteria.

The MTD will be the highest dose level at which 0/3 or 1/6 subjects experience a dose limiting toxicity (DLT). Data will be summarized using descriptive statistics for continuous variables and frequencies, percentages for discrete variables, and presented by dose group, as appropriate.

Radiological response will be assessed by RECIST 1.1 criteria and will be graded as CR, PR, SD and PD. Point estimates and exact binomial 90% confidence intervals will be provided.

Radiological response will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria and will be graded as complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). Point estimates and exact binomial 90% confidence intervals will be provided.

The method of Kaplan and Meier will be used to estimate duration of response in those that achieve PR or CR.

The method of Kaplan and Meier will be used to estimate overall survival in all patients.

Will be compared to those in pre-treatment biopsies using paired statistics such as the Wilcoxon signed-rank test.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Testing a New Anti-cancer Drug Combination, Entinostat and GSK525762C, for Advanced and Refractory Solid Tumors and Lymphomas	NCT03925428	Advanced Lympho... Advanced Malign... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Refractory B-Ce... Refractory Lymp... Refractory Mali... Refractory Panc... Refractory T-Ce... Stage II Pancre... Stage IIA Pancr... Stage IIB Pancr... Stage III Pancr... Stage IV Pancre... Unresectable Pa...	Entinostat Molibresib	12 Years -	National Cancer Institute (NCI)
Compassionate Use Individual Request Program for GSK525762 in NUT Midline Carcinoma	NCT03702036	Solid Tumours	molibresib	16 Years -	GlaxoSmithKline
Compassionate Use Individual Request Program for GSK525762 in NUT Midline Carcinoma	NCT03702036	Solid Tumours	molibresib	16 Years -	GlaxoSmithKline
Testing a New Anti-cancer Drug Combination, Entinostat and GSK525762C, for Advanced and Refractory Solid Tumors and Lymphomas	NCT03925428	Advanced Lympho... Advanced Malign... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Refractory B-Ce... Refractory Lymp... Refractory Mali... Refractory Panc... Refractory T-Ce... Stage II Pancre... Stage IIA Pancr... Stage IIB Pancr... Stage III Pancr... Stage IV Pancre... Unresectable Pa...	Entinostat Molibresib	12 Years -	National Cancer Institute (NCI)
Testing of the Addition of a New Anti-cancer Drug, Molibresib, to Chemotherapy Treatment (Etoposide and Cisplatin) for Patients With NUT Carcinoma	NCT04116359	Metastatic NUT ... Unresectable NU...	Cisplatin Etoposide Etoposide Phosp... Molibresib Molibresib Besy...	12 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for molibresib

Every month we try and update this database with for molibresib cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for molibresib

Every month we try and update this database with for molibresib cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for molibresib cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.