Solid Tumors
Conditions
Brief summary
This is a Phase I, open-label, dose escalation study of ASLAN001 given in combination with CAPOX or mFolfox6, in patients with metastatic solid tumours, whom are suitable to receive CAPOX or mFolfox6, or with tumours that have dysregulated EGFR or HER2 signaling.
Detailed description
The study will use standard 3+3 design to determine the MTD (maximum tolerated dose) of ASLAN001 in combination with fixed dose of Oxaliplatin/Capecitabine (CAPOX) or 5-FU/leucovorin (mFolfox6). MTD of ASLAN001 in combination with CAPOX will first be determined followed by the combination with mFolfox6. The recommended Phase II dose will be the highest dose of the combination therapy that is considered to be tolerated in 6 patients.
Interventions
DRUGASLAN001+ CAPOX (Oxaliplatin, capecitabine)
ASLAN001 in combination with oxaliplatin and capecitabine
DRUGASLAN001 + mFolfox6 (5-FU, leucovorin)
ASLAN001 in combination with 5-FU and leucovorin
Sponsors
ASLAN Pharmaceuticals
National Medical Research Council (NMRC), Singapore
National Cancer Centre, Singapore
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients with metastatic solid tumours eligible for treatment with oxaliplatin in combination with capecitabine / 5-FU (fluorouracil) and leucovorin or who progressed following standard therapy or patients with EGFR (epidermal growth factor receptor ) or HER2 dysregulated tumours. 2. 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
. 3. Eastern Cooperative Oncology Group performance status of 0 or 1. 4. 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: Prothrombin time and activated partial thromboplastin time ≤ 1.5 x upper limit of normal (ULN) per institutional laboratory normal range. • 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. Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x ULN (≤ 5 x ULN if liver metastases are present). 5. Patients undergoing mandatory biopsy in dose expansion of a non-DLT cohort should have any of the following: * known HER2 or EGFR dysregulation * Patients with T790M mutation will be excluded. * Co-expression of HER2 and EGFR 6. Archival tumour sample is available for molecular profiling, unless undergoing tumour biopsy as part of the trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum tolerated dose (MTD) of ASLAN001 when used in combination with Oxaliplatin and Capecitabine (CAPOX) or Oxaliplatin and 5-FU with leucovorin (mFolfox6) | one year |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetic parameter Area under the plasma concentration time curve (AUC) | Day 1 and Day 15 of Cycle 1 and Day 1 of Cycle 3 |
| Pharmacokinetic parameter Maximum plasma concentration (Cmax) | Day 1 and Day 15 of Cycle 1 and Day 1 of Cycle 3 |
| Pharmacokinetic parameter Minimum (trough) plasma concentration (Cmin) | Day 1 and Day 15 of Cycle 1 and Day 1 of Cycle 3 |
| Efficacy of ASLAN001 when given in combination in CAPOX or mFolfox6 as measured by the objective response rate (ORR) | one year |
Countries
Singapore
Outcome results
None listed