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

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

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.

Study Overview

• Status: Terminated
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: EMD 1204831

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.

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States
      • M.D. Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1	Drug: EMD 1204831; Subjects will receive EMD 1204831 twice a day for 21 days during each treatment cycle

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	Time Frame
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.
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.
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.

Collaborators and Investigators

• Sponsor: EMD Serono
• Investigators: Study Director: Manfred Klevasath, MD, Merck KGaA, Darmstadt, Germany

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): March 1, 2012

Study Registration Dates

• First Submitted: April 19, 2010
• First Submitted That Met QC Criteria: April 22, 2010
• First Posted (Estimate): April 26, 2010

Study Record Updates

• Last Update Posted (Estimate): October 22, 2013
• Last Update Submitted That Met QC Criteria: October 21, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• 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
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: EMR200096-001