A phase I/II open-label, dose escalation study to investigate the safety, pharmacokinetics, pharmacodynamics and clinical activity of GSK525762 in subjects with NUT midline carcinoma (NMC) and other cancers

GlaxoSmithKline Research and Development Ltd0 sites196 target enrollmentApril 28, 2015

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Not specified
Sponsor: GlaxoSmithKline Research and Development Ltd
Enrollment: 196
Status: Active, not recruiting
Last Updated: 6 years ago

Overview Investigators Eligibility Criteria Outcomes Similar Trials

Overview

Brief Summary

No summary available.

Registry

who.int

Start Date

April 28, 2015

End Date

TBD

Last Updated

6 years ago

Study Type

Interventional clinical trial of medicinal product

Investigators

Sponsor

GlaxoSmithKline Research and Development Ltd

Eligibility Criteria

Inclusion Criteria

•1\. Male or female 16 years or older, at the time of signing the informed consent.
•2\. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. If the subject is less than 18 years old, an Assent form and parental/guardian Consent form (replacing you will” with your child will” will be required).
•3\. Diagnosis of one of the following:
•Part 1 Only:
•\- NUT Midline Carcinoma based on ectopic expression of NUT protein as determined by IHC and/or detection of NUT gene translocation as determined by FISH. Subjects may be treatment naïve or have had prior therapy.
•\- SCLC, CRC, NB, TNBC, ER positive BC, CRPC, NSCLC, and any other solid tumor which has been confirmed by clinical testing to be MYCN amplified (defined as a MYCN gene copy number gain of \=5\). Subjects should have tumor progression after receiving at least one prior standard/approved chemotherapy, or where there is no approved therapy, or where standard therapy is refused.
•Part 2 Only:
•\- NUT Midline Carcinoma as diagnosed by the Central Laboratory. Subjects may be treatment naïve or have had prior therapy.
•\- SCLC, CRPC, TNBC and ER\+BC
•4\. Subjects with solid tumors, with the exception of CRPC, must demonstrate measurable disease, per RECIST v1\.1\. NOTE: Subjects with NMC that do not meet the RECIST v1\.1 criteria for measurable disease, but have evaluable disease may be considered for enrollment after discussion with the GSK medical monitor.

Exclusion Criteria

•1\. Primary malignancy of the central nervous system, or malignancies related to HIV or solid organ transplant. History of known HIV. History of known Hepatitis B surface antigen or positive Hepatitis C antibody (confirmed by RIBA).
•2\. Prior treatments usage as defined:
•a. Use of an investigational anti\-cancer drug within 14 days or 5 half\-lives, whichever is longer, prior to the first dose of the investigational products.
•b. A minimum of 14 days between termination of the investigational drug and administration of GSK525762\.
•c. Any therapy related toxicities must also have resolved to Grade 1 or less. Note that an investigational drug is defined as a drug without an approved oncologic indication.
•d. Chemotherapy, radiotherapy, anti\-neoplastic antibody or targeted therapy or immunotherapy within 14 days, major surgery within 28 days (or 42 days for prior nitrosoureas or mitomycin C) prior to the first dose of the investigational product.
•e. Anti\-androgen (e.g., bicalutamide) therapies for prostate cancer must be stopped 4 weeks prior to enrollment. Second line hormone therapies such as enzalutamide, abiraterone, or orteronel should be stopped 2 weeks prior to enrollement. Subjects with prostate cancer should remain on luteinizing hormone releasing hormone (LHRH) agonists or antagonists. Subjects with prostate cancer may also remain on low\-dose prednisone or prednisolone (up to 10 mg/day) and still be eligible for this study.
•3\. Current use of anticoagulants (e.g., warfarin, heparin) at therapeutic levels within 7 days prior to the first dose of GSK525762\. Low dose (prophylactic) low molecular weight heparin (LMWH) is permitted. In addition, INR must be monitored in accordance with local institutional practices.
•4\. Current use of a prohibited medication or requires any of these medications during treatment with the investigational drugs (details will be available in Section 8\.3\). This includes excluding current medications known or suspected to be associated QT prolongation. In addition, any subject who may require a QT prolonging medication while on trial should not be enrolled.
•5\. Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated respiratory, hepatic, renal, cardiac disease, or clinically significant bleeding episodes). Any serious and/or unstable pre\-existing medical (aside from malignancy exception above), psychiatric disorder, or other conditions that could interfere with subject’s safety, obtaining informed consent or compliance to the study procedures, in the opinion of the Investigator.