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

Solid Tumors Clinical Trial

Official title:

A Phase I Open-label, Non-randomized, Dose-escalation First-in-man Trial to Investigate the c-Met Kinase Inhibitor EMD 1204831 in Subjects With Advanced Solid Tumors

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01110083
• Other study ID #: EMR200096-001
• Status: Terminated
• Phase: Phase 1
• First received: April 19, 2010
• Last updated: October 21, 2013
• Start date: April 2010

Study information

• Verified date: October 2013
• Source: EMD Serono
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 38
• Est. primary completion date: March 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Solid Tumors

Intervention

Drug:
• EMD 1204831
Subjects will receive EMD 1204831 twice a day for 21 days during each treatment cycle

Locations

Country	Name	City	State
United States	M.D. Anderson Cancer Center	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
EMD Serono

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine the maximum tolerated dose (MTD) of EMD 1204831 in subjects with advanced solid tumors		After first cycle of treatment	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No