Background
Methods/Design
Trial design
CTCAE Term | CTCAE version 5.0 |
---|---|
Hematological toxicity | |
Febrile neutropenia | grade ≥ 3 |
Neutrophil count decreased | grade ≥ 3 for > 7 days |
WBC decreased | grade ≥ 3 |
Platelet count decreased | grade ≥ 3 |
grade < 3 requiring blood transfusion | |
Anemia | grade ≥ 3 |
Non-hematological toxicity | |
ECG QT corrected interval prolonged | grade ≥ 3 |
Nausea | grade ≥ 3 for > 7 days despite the adequate and optimal therapy |
Tumor pain | grade ≥ 3 for > 7 days despite the adequate and optimal therapy |
Vomiting | grade 3 for > 7 days despite the adequate and optimal therapy, or grade ≥ 4 |
Diarrhea or associated electrolyte abnormalities | grade ≥ 3 for > 2 days despite the adequate and optimal therapy |
Fatigue | grade ≥ 3 for > 7 days |
Anorexia | grade ≥ 3 for > 7 days |
Hypophosphatemia, hypomagnesemia, or hypocalcemia | grade ≥ 3 for > 2 days despite the adequate and optimal therapy |
Asymptomatic AST, ALT, ALP, or GGT | grade ≥ 3 for > 7 days |
Baseline AST or ALT ≥ 2.5 to 5 X ULN in patients with confirmed liver metastases | AST or ALT > 8 X ULN for > 7 days |
Baseline ALP ≥ 2 to 5 X ULN in patients with confirmed liver metastases | ALP > 8 X ULN for > 7 days |
All the other ADRs excluding above | grade ≥ 3 |
Other toxicity | |
ADR with dose interruption (temporary discontinuation) of PHI-101 for > 4 weeks |
Participants
Major inclusion criteria
Major Exclusion Criteria
Primary Endpoints
Primary objectives
Secondary objectives
Sample size
Dose level (cohort) | Daily dose of PHI-101 (once daily) | Escalation increment from the previous dose | ||
---|---|---|---|---|
-1 | 20 mg | 1 tab. | - 20 mg | - 50% |
1 (starting dose) | 40 mg | 2 tab. | - | - |
2 | 80 mg | 4 tab. | 40 mg | 100% |
3 | 120 mg | 6 tab. | 40 mg | 50% |
4 | 160 mg | 8 tab. | 40 mg | 33% |
5 | 200 mg | 10 tab. | 40 mg | 25% |
6 (maximum planned dose) | 240 mg | 12 tab. | 40 mg | 20% |