Clinical study using the drug GSK525762 in Subjects with cancer
- Conditions
- T Midline Carcinoma and other solid tumorsMedDRA version: 18.0 Level: LLT Classification code 10007284 Term: Carcinoma System Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-004982-25-GB
- Lead Sponsor
- GlaxoSmithKline Research and Development Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 196
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.
5. All prior treatment- related toxicities must be CTCAE (Version 4.0) = Grade 1 (except alopecia and peripheral neuropathy) at the time of treatment allocation.
6. ECOG Performance Status score of 0 to 2 for subjects with NMC; 0-1 for subjects with other tumor types.
7. Adequate organ function as defined in Table 8.
See table in the protocol
8. Able to swallow and retain orally administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels.
9. A female subject is eligible to participate if she is of:
- Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) >40 MlU/ml and estradiol <40 pg/ml (<140 pmol/L) is confirmatory]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use study. Otherwise, they must discontinue HRT to allow confirmation of postmenopausal status prior to study enrollment. For most forms of HRT, at least 2 to 4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, th
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.
6. Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression.
NOTE: Subjects previously treated for these conditions that have had stable CNS disease (verified with consecutive imaging studies) for >1months, are asymptomatic and off corticosteroids, or are on stable dose of corticosteroids for at least 1 month prior to study Day 1 are permitted. Stability of brain metastases must be confirmed with imaging. Subject treated with gamma knife the can be enrolled 2 weeks postprocedure as long as
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method