Table 2. Clinical trials.
| Identifier | Acronym | Phase | Number of Patients | Therapy Class | Therapy Agent | Dosing Schedule | Primary (P)/Secondary (S) Endpoints | Results |
|---|---|---|---|---|---|---|---|---|
| NCT01283516 | ASCEND1 | I | 246 | Tyrosine Kinase Inhibitor | Ceritinib | 750 mg daily | P: Dose Limiting Toxicities (DLT); Overall Response Rate (ORR); Duration of Response (DOR) S: Drug Related Adverse Events; Absorption and Plasma Concentration of LDK378 |
DLT: 8 Pts ORR: 56.4% (All Pts) Median DOR: 7.39 mos (All Pts) Median PFS: 18.4 mos – ALK Pretreated Most Common AE: Elevation of AST/ALT Levels |
| NCT01685060 | ASCEND2 | II | 140 | Tyrosine Kinase Inhibitor | Ceritinib | 750 mg daily | P: ORR S: DOR; Disease Control Rate (DCR); Time to Response (TTR); Safety Profile; PFS; OS; Overall Intracranial Response Rate (OIRR) |
ORR: 38.6% (All Pts) DCR: 77.1% (All Pts) Median DOR: 9.7 mos (All Pts) Median PFS: 9.7 mos (All Pts) Most Common AE: Nausea, Diarrhea, Vomiting |
| NCT01685138 | ASCEND3 | II | 124 | Tyrosine Kinase Inhibitor | Ceritinib | 750 mg daily | P: ORR S: DOR; Disease Control Rate (DCR); Time to Response (TTR); Safety Profile; PFS; OS; Overall Intracranial Response Rate (OIRR) |
ORR: 63.7% (All Pts) DCR: 89.5% (All Pts) Median DOR: 9.3 mos (All Pts) Median PFS: 11.1 mos (All Pts) Most Common AE: Diarrhea, Nausea, Vomiting |
| NCT01828099 | ASCEND4 | III | 376 | Tyrosine Kinase Inhibitor | Ceritinib | 750 mg daily | P: PFS S: OS; ORR; DOR; DCR: TTR |
Median PFS: Ceritinib (16.5 mos) vs Chemo (8.1 mos) OS: Ceritinib (29.3 mos) vs Chemo (26.2 mos) ORR: 72.5% (Ceritinib) DCR: 84.7% (Ceritinib) DOR: 23.9 mos (Ceritinib) Most Common AE: Diarrhea, Nausea, Vomiting |
| NCT01828112 | ASCEND5 | III | 231 | Tyrosine Kinase Inhibitor | Ceritinib | 750 mg daily | P: PFS S: OS; ORR; DOR; DCR: TTR |
Median PFS: Ceritinib (5.4 mos) vs Chemo (1.6 mos) ORR: 39.1% (Ceritinib) DCR: 76.5% (Ceritinib) Most Common AE: Diarrhea, Nausea, Vomiting |
| NCT02616393 | II | 60 | Tyrosine Kinase Inhibitor | Tesevatinib | P: Clinical Activity Against BM and LM S: Quality of Life Assessments; PFS; OS |
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| II | 19 | Folate Antimetabolite | Temozolomide | One cycle of oral TMZ (100 mg/m(2) daily) one week on treatment/one week off treatment for four weeks. | Study stopped early due to poor accrual. 3 of 19 Pts demonstrated clinical benefit. | |||
| NCT00424242 | I | 15 | Folate Antimetabolite | Pemetrexed | P: Correlation of CSF with Plasma Levels of Different Doses; Anti-Tumor activity against LM; Safety Profile; Assess role of Serum Biomarkers in Pts with LM | |||
| NCT01281696 | I/II | 8 | Monoclonal Antibody | Bevacizumab | Bevacizumab (Day 1), Etoposide (Days 2-4), and Cisplatin on Day 2 in a 21-day cycle for 6 cycles. | P: CNS Response Rate | CNS Response Rate: 60% in 5 evaluable pts. Median OS: 4.7 mos Neurologic PFS: 4.7 mos Most Common AE: Neutropenia, Leukopenia, Hyponatremia |
|
| NCT01325207 | I/II | 34 | Monoclonal Antibody | Trastuzamab | 10–500 mg Twice Weekly | P: Safety and maximum tolerated dose of intrathecal (IT) Trastuzumab S: Response to IT Trastuzumab; CSF Pharmokinetic of IT Trastuzumab |