Solid Tumor
Conditions
Keywords
ASLAN001, Varlitinib
Brief summary
This is a phase IB study to assess the safety and tolerability of ASLAN001 when given in combination with either Cisplatin and 5-Fluorouracil or Cisplatin and Capecitabine, with a view to identifying the recommended Phase II dose.
Detailed description
This is an open-label, Phase I, dose escalation study of ASLAN001 given in combination with Regimen A or Regimen B, in patients with metastatic solid tumors, eligible to receive the cisplatin/5-fluorouracil or cisplatin/capecitabine regimen. Dose of ASLAN001 starts from 400mg BID; then, dose escalation to 500mg BID or dose de-escalation to 300mg BID will depend on DLTs observed in cohort. Regimen A: Depends on preferred medical practice, Cohort 1A will receive ASLAN001 400 mg BID in combination with cisplatin 80 mg/m2 IV infusion and 5 fluorouracil 800 mg/m2/day IV infusion for 5 days every 3 weeks; or will receive ASLAN001 400 mg BID in combination with Cisplatin 35 mg/m2 24-hour infusion for day 1 and day 8, 5-fluorouracil 2,000 mg/m2 and Leucovorin 300mg/m2 24-hour infusion for day 1, day 8 and day 15 every 4 weeks. Regimen B: Cohort 1B will receive ASLAN001 400 mg BID in combination with cisplatin 80 mg/m2 IV infusion and oral capecitabine 1,000 mg/m2 BID for 14 days every 3 weeks.
Interventions
DRUGASLAN001
ASLAN001 400mg BID daily; ASLAN001 500mg BID daily; or ASLAN001 300mg BID daily
Cisplatin 80 mg/m2 IV infusion and capecitabine 1,000 mg/m2 orally BID for 14 days every 3 weeks
DRUGcisplatin + 5-fluorouracil (or+ Leucovorin)
Cisplatin 80 mg/m2 IV infusion and 5-fluorouracil 800 mg/m2/day IV infusion for 5 days every 3 weeks; Or Cisplatin 35 mg/m2 24-hour infusion for day 1 and day 8, 5-fluorouracil 2,000 mg/m2 and Leucovorin 300mg/m2 24-hour infusion for day 1, day 8 and day 15 every 4 weeks.
Sponsors
ASLAN Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female patients 20 years of age or older at the time written informed consent is obtained. 2. Regimen A: Patients with metastatic solid tumors eligible for treatment with cisplatin and 5-fluorouracil. The standard dose and schedule of cisplatin and 5-fluorouracil will be according to the preference of investigators and institutions. Regimen B: Patients with metastatic solid tumors eligible for treatment with cisplatin in combination with capecitabine. 3. Patients with a partial gastrectomy may be allowed to participate in the study as long as they can take oral medications and meet all other inclusion/
Exclusion criteria
. 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 5. Adequate organ and hematological function as evidenced by the following laboratory studies within 14 days prior to enrolment: Hematological function, as follows: * Absolute neutrophil count ≥ 1.5 x 109/L. * Platelet count ≥ 100 x 109/L. * Hemoglobin ≥ 9 g/dL. Coagulation function, as follows: * Partial thromboplastin time or activated partial thromboplastin time ≤ 1.5 x upper limit of normal (ULN) per institutional laboratory normal range. * International normalized ratio ≤ 1.5. Renal function, as follows: • Creatinine clearance ≥ 50 mL/min as calculated by Cockcroft-Gault formula. Hepatic function, as follows: * Total bilirubin ≤ 1.5 x ULN. * AST and ALT ≤ 2.5 x ULN (≤ 5 x ULN if liver metastases are present).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of ASALN001 | First 2 cycles | Safety and tolerability as evaluated with: DLTs (in first 2 cycles); Maximum tolerated dose (MTD) of ASLAN001 in combination with cisplatin/capecitabine or cisplatin/5-FU will be determined. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics profile (AUC) of ASLAN001 | Along the study duration | To evaluate the pharmacokinetics of ASLAN001, when given in combination with Regimen A or Regimen B. Pharmacokinetic parameters including, but not limited to area under the plasma concentration-time curve (AUC) from 0 to 6 hours (AUC0-6). |
| Pharmacokinetics profile (Cmax) of ASLAN001 | Along the study duration | To evaluate the pharmacokinetics of ASLAN001, when given in combination with Regimen A or Regimen B. Pharmacokinetic parameters including, but not limited to maximum plasma concentration (Cmax). |
| Preliminary assessment of the efficacy | Along the study duration | •To provide a preliminary assessment of the efficacy of ASLAN001 when given in combination in Regimen A or Regimen B as measured by the objective response rate (ORR). |
| Pharmacokinetics profile (RacAUC0-6) of ASLAN001 | Pharmacokinetic measurements will be from Cycle 1 Day 1 to Cycle 3 Day 1 (each cycle is 28 days for Amended Regimen A, and 21 days for Regimen A and B. | To evaluate the pharmacokinetics of ASLAN001, when given in combination with Regimen A or Regimen B. Pharmacokinetic parameters including, but not limited to accumulation ratio for AUC (RacAUC0-6). |
| Pharmacokinetics profile (Tmax) of ASLAN001 | Along the study duration | To evaluate the pharmacokinetics of ASLAN001, when given in combination with |
| Pharmacokinetics profile (Cmin) of ASLAN001 | Along the study duration | To evaluate the pharmacokinetics of ASLAN001, when given in combination with Regimen A or Regimen B. Pharmacokinetic parameters including, but not limited to minimum (trough) plasma concentration (Cmin). |
Countries
Hong Kong, Taiwan
Outcome results
None listed