First-in-Man, Dose-escalation Trial of c-Met Kinase Inhibitor EMD 1204831 in Subjects With Advanced Solid Tumors

Inclusion Criteria:

Main Inclusion Criteria

1. Histologically or cytologically confirmed solid tumor, either refractory standard therapy or for which no effective standard therapy is available
2. Measurable or evaluable disease, as defined by RECIST 1.0
3. Men or women aged ≥ 18 years
4. ECOG performance status of 0 to 2
5. Adequate hematological function: Hemoglobin ≥ 9.0 g/dL; Neutrophils \> 1.5 x 109/L; Platelets ≥ 100 x 109/L
6. Adequate liver function: Total bilirubin ≤ 1.5 x ULN; AST/ ALT ≤ 2.5 x ULN
7. For subjects with liver metastases: Total bilirubin ≤ 1.5 x ULN; AST/ALT ≤ 5 ULN
8. Adequate renal function: Serum creatinine \< 1.5 x ULN, and/or Calculated creatinine clearance \> 60 mL/min
9. Resolution of all acute chemotherapy, radiotherapy or surgery-related AEs to Grade ≤1, except for alopecia
10. Recovery from any surgical intervention
11. Subjects enrolling after the MTD has been determined must present specific c-Met alterations (overexpression, amplification, mutation)

Exclusion Criteria:

Main Exclusion Criteria

1. Received chemotherapy, immunotherapy, hormonal therapy (except subjects with prostate cancer), biologic therapy, or any other investigational agent or anticancer therapy within 28 days (or five half-lives for non-cytotoxics, whichever is shorter), of Day 1 of trial treatment (six weeks for nitrosureas or mitomycin C)
2. Received extensive prior radiotherapy on more than 30% of bone marrow
3. Symptomatic primary tumors or metastasis of brain and/or central nervous system, uncontrolled with antiepileptics and requiring high doses of steroids
4. Medical history of liver fibrosis/ cirrhosis
5. Medical history of surgery within six weeks prior to enrollment
6. Neuropathy Grade ≥ 2
7. Requires concurrent treatment with a non-permitted drug
8. Absence or abnormal pupillary reflex