Solid Tumors
Conditions
Keywords
Phase 1, advanced solid tumors, refractory to standard therapy, Patients with solid tumors, either refractory to standard therapy or for which no effective standard therapy is available
Brief summary
EMD Serono has closed enrollment into this trial prior to determination of maximum tolerated dose (MTD). EMD Serono has decided not to pursue the development of EMD 1204831 in patients with advanced solid tumors for reasons other than safety.
Detailed description
This is a an open-label, dose-escalation, first-in-man (FIM) study designed to explore the safety, tolerability, pharmacokinetics, and clinical activity of an investigational drug, EMD 1204831, in patients with advanced solid tumors who have not responded to previous therapies or for whom no other therapies are available. Subjects will receive EMD 1204831 twice a day (BID) during each 21-day cycle until disease progression or unacceptable toxicity.
Interventions
DRUGEMD 1204831
Subjects will receive EMD 1204831 twice a day for 21 days during each treatment cycle
Sponsors
EMD Serono
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To determine the maximum tolerated dose (MTD) of EMD 1204831 in subjects with advanced solid tumors | After first cycle of treatment |
Secondary
| Measure | Time frame |
|---|---|
| PK parameters will be assessed to characterize the pharmacokinetic (PK) profile of EMD 1204831 and summarized by dose level and cycle. | Scheduled visits throuhout each 21 day cycle of treatment. Subjects may continue to receive cycles of EMD 1204831 until disease progression or unacceptable toxicity. |
| Number and frequency of adverse events, and changes from baseline in laboratory values, vital signs and ECGs will be used to assess safety and tolerability of EMD1204831. | Scheduled visits throuhout each 21 day cycle of treatment. Subjects may continue to receive cycles of EMD 1204831 until disease progression or unacceptable toxicity. |
| Anti-tumor activity and best overall response will be assessed according to RECIST 1.0 after every two cycles of EMD 1204831. Frequency of subjects with different levels of overall response (CR, PR, SD or PD) and best Overall Response will be presented. | Scheduled visits throuhout each 21 day cycle of treatment. Subjects may continue to receive cycles of EMD 1204831 until disease progression or unacceptable toxicity. |
| Values and changes over time in pharmacodynamic (Pd) markers in tissue and molecular markers in blood will be assessed | Scheduled visits throuhout each 21 day cycle of treatment. Subjects may continue to receive cycles of EMD 1204831 until disease progression or unacceptable toxicity. |
| Exploratory analyses of genes that may be involved in the absorption, distribution, metabolism, and elimination (ADME) of EMD 1204831 will be performed. | Scheduled visits throuhout each 21 day cycle of treatment. Subjects may continue to receive cycles of EMD 1204831 until disease progression or unacceptable toxicity. |
Countries
United States
Outcome results
None listed