Primary:To evaluate the clinical activity of GSK525762 in NUT Midline Carcinoma and other solid tumors.Secondary:Effect of treatment with GSK525762 on tumor growth and survival. Pharmacokinetics of GSK525762. Safety.
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Adverse events. Overall response rate.
Secondary outcome
PK parameters, cardiac safety parameters, progression free survival, time to
and duration of response, overall survival.
Background summary
Given the poor prognosis and high unmet medical need of NUT Midline Carcinoma
(NMC), as well as in other tumor types such as relapsed/refractory (Non) small
cell lung cancer ([N]SCLC), colorectal cancer (CRC), neuroblastoma (NB),
castration resistant prostate cancer (CRPC), triple negative breast cancer
(TNBC), ER positive breast cancer (ER+BC) and any other MYCN-amplified solid
tumor and the exceptional drug-to-target alignment of GSK525762, a combined
Phase I/II study (BET115521) is proposed. The BET115521 study comprises
• An accelerated dose titration (Part 1), which will include subjects with NMC
and other tumor types that are predicted to be responsive to GSK525762, to
determine a maximum tolerated dose (MTD).
The besylate sub-study will be an open-label, randomized, single dose, four
period, crossover sub-study to investigate the relative bioavailability of the
besylate salt tablet compared to the amorphous free-base tablet. Results of the
besylate sub-study will enable the use of the besylate salt tablet formulation
later in this study and provide recommendation around the need for fasting
status when administering GSK525762. The besylate sub-study will be conducted
at centers in the United States.
• Part 2 is the expansion phase to further explore the efficacy and safety of
the MTD in subjects with NMC, SCLC, CRPC, TNBC en ER+BC.
The Netherlands will contribute to Part 2 only. This ABR-form is restricted to
information about Part 2.
Study objective
Primary:
To evaluate the clinical activity of GSK525762 in NUT Midline Carcinoma and
other solid tumors.
Secondary:
Effect of treatment with GSK525762 on tumor growth and survival.
Pharmacokinetics of GSK525762. Safety.
Study design
Part 2 is the expansion phase to further explore the efficacy and safety of the
MTD.
Continuation of treatment until disease progression or unacceptable toxicity.
Approx.150 subjects for part 2.
Intervention
Treatment with GSK525762.
Study burden and risks
Risk: Adverse events of study medication.
Burden:
Twice per week during week 1-2, weekly during week 3-4, every 4 week thereafter.
Physical examination: Nearly every visit.
Blood tests: Every visit. Up to 35 mL per visit.
ECG: Nearly every visit.
Echocardiography: Approx. every 4 weeks.
Holter monitoring 24h: Twice.
Tumor measurements: Every 4-8 weeks.
Tumor biopsy: 2-3 times.
Optional: Pharmacogenetic blood test (6 mL once).
Huis ter Heideweg 62
Zeist 3705 LZ
NL
Huis ter Heideweg 62
Zeist 3705 LZ
NL
Listed location countries
Age
Inclusion criteria
• Males and females, 16 years and above (NL: 18 years and above).
• Diagnosis:
NUT Midline Carcinoma as diagnosed by the Central Laboratory. Subjects may be treatmentnaïve or have had prior therapy.
SCLC, CRPC, TNBC and ER+BC
• Subjects with solid tumors, with the exception of CRPC, must demonstrate measurable disease (NMC: see protocol page 50 for details).
• ECOG Performance Status 0-2 (NMC), 0-1 (other tumor types).
• Females of childbearing potential and males: adequate method of contraception.
• CRPC subjects:
Histologically or cytologically confirmed prostate adenocarcinoma, surgically castrated or continuously medically castrated (for *8 weeks)
Persistent disease with evidence of disease progression following standard therapy(ies). See protocol page 52 for details.
Serum testosterone level <1.7 nmol/l.
PSA level >=2.0 ng/mL.
Exclusion criteria
• Prior and current treatments: see protocol page 53 for details.
• Evidence of severe or uncontrolled systemic diseases. See protocol page 53 for details.
• Cardiac and or ECG abnormalities. See protocol page 54 for details.
• GSK525762 is a benzodiazepine class molecule. Any serious known immediate or delayed hypersensitivity reaction(s) to GSK525762 or idiosyncrasy to drugs chemically related to the investigational drug.
• Hemoptysis > 1 teaspoon in 24 hours within the last 28 days.
• History of major gastrointestinal bleeding within the last 6 months. Any evidence of active gastrointestinal bleeding.
• Pregnancy or breastfeeding.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | clinicaltrials.gov; NCT01587703 |
| EudraCT | EUCTR2014-004982-25-NL |
| CCMO | NL53261.031.15 |