Solid Malignancies including Bladder Cancer
Conditions
Interventions
Product Name: Guadecitabine (SGI-110)
Product Code: SGI-110
Pharmaceutical Form: Powder for injection
INN or Proposed INN: Guadecitabine
CAS Number: 929904-85-8
Other descriptive name: SGI-110
Concent
Sponsors
University Hospital Southampton NHS Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: All Patients: 1. ECOG performance status of 0 or 1 2. Glomerular filtration rate estimation of = 60 mL/min according to either the Cockcroft and Gault formula or by Cr-51 EDTA or Tc-99m DTPA clearance 3. Adequate haematological parameters • Haemoglobin = 90 g/dL • Neutrophil count = 1.5 x109/L • Platelets = 100 x109/L 4. Adequate biochemical parameters • Bilirubin = 1.5 x ULN • ALT and ALP = 2.5 x ULN (ALP = 5 x ULN if caused by liver or bone metastases) 5. Aged 16 years or over 6. Life expectancy > 3 months 7. Provision of written informed consent Patients In The Dose Escalation Phase: 8. Incurable histologically or cytologically confirmed, locally advanced or metastatic, solid cancer, for which the use of gemcitabine and cisplatin is a clinically appropriate treatment in the view of the local principal investigator. Any number of previous lines of systemic chemotherapy is permitted. Patients In The Dose Expansion Phase: 9. Bladder cancer with a pure or a predominant component of transitional cell carcinoma 10. Clinical stage T2-4a N0 M0 11. Planned to commence GC for 3 or 4 cycles with neoadjuvant (i.e. curative) intent prior to a planned radical cystectomy Are the trial subjects under 18? yes Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 35 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 21
Exclusion criteria
Exclusion criteria: All Patients: 1. Unresolved toxicities from prior therapy greater than CTCAE v4.03 grade 1 (with the exception of alopecia) at the time of registration 2. Prior radiotherapy to > 30% of bone marrow 3. Major surgery within 30 days 4. Any investigational medicinal product within 30 days 5. Allergy or other known intolerance to any of the proposed study drugs including supportive agents and inclusive of G-CSF and locally utilised anti-emetics 6. Previously-identified central nervous system metastases unless treated and clinically stable and not requiring steroids for at least 4 weeks prior to the start of trial treatment 7. Coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, unstable angina pectoris or congestive cardiac failure (New York Heart Association = grade 2) within the last 6 months 8. Women who are pregnant or breast feeding. (Women of child-bearing potential must have a negative pregnancy test performed within 7 days prior to the start of trial treatment) 9. Patients of child-bearing potential who are not using, or who are unwilling to use, a highly effective method of contraception 10. Any patient who, in the judgment of the local investigator, is unlikely to comply with trial procedures, restrictions or requirements Patients In The Dose Expansion Phase: 11. Recent or current separate other malignancy. Current non-melanoma skin cancer, cervical carcinoma in situ or incidental localised prostate cancer is permissible. Participants with a history of a separate other malignancy having completed all active treatment 2 or more years previously may be entered
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To find a safe and effective dose of the trial drug when given in combination with gemcitabine and cisplatin chemotherapy.;Secondary Objective: To find out about potential side effects of the combination of the SGI-110 and gemcitabine/cisplatin chemotherapy. To understand the effect that the combination of SGI-110 drug and chemotherapy have on blood and cancerous tissue. To understand how SGI-110 is processed through the body To evaluate whether it is safe and feasible to administer SGI-110 and chemotherapy to patients with muscle invasive bladder cancer prior to them having cystectomy. ;Primary end point(s): To establish a recommended phase II dose and schedule (RP2D) for SGI-110 when combined with GC chemotherapy from both: • the MTD based on defined criteria for dose limiting toxicity (DLT) assessed by Common Terminology Criteria for Adverse Events (CTCAE) v4.03 and • the Maximally Biologically Effective Dose (MBED) based on plasma DNA LINE-1 methylation and haemoglobin F (HbF) re-expression status ;Timepoint(s) of evaluation of this end point: Patients assessed for toxicity throughout treatment until the last dose of last patient in the dose escalation phase. This may be through reaching the final cohort or meeting the stopping rules for cohorts 1, 2 or 3. Blood samples will be taken according to protocol for pharmacodynamics analysis. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Toxicity of SGI-110 in combination with gemcitabine and cisplatin chemotherapy in comparison to the chemotherapy alone. 2. Pharmacokinetics of SGI-110 when in combination with GC 3. Pathological complete response rates (dose expansion phase) 4. Biomarker Assessment of SGI-110 ;Timepoint(s) of evaluation of this end point: 1. Patients assessed for toxicity throughout treatment until the last dose of last patient in the dose escalation phase. This may be through reaching the final cohort or meeting the stopping rules for cohorts 1, 2 or 3. 2. Blood samples will be taken according to protocol for pharmacokinetics analysis. 3. Pathology reports from surgical resections 4. Tissue samples collected at surgery and archival biopsy samples | — |
Countries
United Kingdom
Contacts
Public ContactKeith Pugh
Southampton Clinical Trials Unit
Outcome results
None listed