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

Purpose

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.

Condition	Intervention	Phase
Solid Tumors	Drug: EMD 1204831	Phase 1


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

Resource links provided by NLM:

MedlinePlus related topics: Cancer

U.S. FDA Resources

Further study details as provided by EMD Serono:

Primary Outcome Measures:

To determine the maximum tolerated dose (MTD) of EMD 1204831 in subjects with advanced solid tumors [ Time Frame: After first cycle of treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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. [ Time Frame: Scheduled visits throuhout each 21 day cycle of treatment. Subjects may continue to receive cycles of EMD 1204831 until disease progression or unacceptable toxicity. ] [ Designated as safety issue: No ]
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. [ Time Frame: Scheduled visits throuhout each 21 day cycle of treatment. Subjects may continue to receive cycles of EMD 1204831 until disease progression or unacceptable toxicity. ] [ Designated as safety issue: No ]
PK parameters will be assessed to characterize the pharmacokinetic (PK) profile of EMD 1204831 and summarized by dose level and cycle. [ Time Frame: Scheduled visits throuhout each 21 day cycle of treatment. Subjects may continue to receive cycles of EMD 1204831 until disease progression or unacceptable toxicity. ] [ Designated as safety issue: No ]
Values and changes over time in pharmacodynamic (Pd) markers in tissue and molecular markers in blood will be assessed [ Time Frame: Scheduled visits throuhout each 21 day cycle of treatment. Subjects may continue to receive cycles of EMD 1204831 until disease progression or unacceptable toxicity. ] [ Designated as safety issue: No ]
Exploratory analyses of genes that may be involved in the absorption, distribution, metabolism, and elimination (ADME) of EMD 1204831 will be performed. [ Time Frame: Scheduled visits throuhout each 21 day cycle of treatment. Subjects may continue to receive cycles of EMD 1204831 until disease progression or unacceptable toxicity. ] [ Designated as safety issue: No ]


Enrollment:	38
Study Start Date:	April 2010
Primary Completion Date:	March 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Arm 1	Drug: EMD 1204831 Subjects will receive EMD 1204831 twice a day for 21 days during each treatment cycle

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.

Eligibility


Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Main Inclusion Criteria

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

Exclusion Criteria:

Main Exclusion Criteria

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)
Received extensive prior radiotherapy on more than 30% of bone marrow
Symptomatic primary tumors or metastasis of brain and/or central nervous system, uncontrolled with antiepileptics and requiring high doses of steroids
Medical history of liver fibrosis/ cirrhosis
Medical history of surgery within six weeks prior to enrollment
Neuropathy Grade ≥ 2
Requires concurrent treatment with a non-permitted drug
Absence or abnormal pupillary reflex

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01110083

Locations


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

Sponsors and Collaborators

EMD Serono

Investigators


Study Director:	Manfred Klevasath, MD	Merck KGaA

More Information

No publications provided


Responsible Party:	EMD Serono
ClinicalTrials.gov Identifier:	NCT01110083 History of Changes
Other Study ID Numbers:	EMR200096-001
Study First Received:	April 19, 2010
Last Updated:	October 21, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by EMD Serono:


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

ClinicalTrials.gov processed this record on February 27, 2015