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

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Solid Tumors	Drug: EMD 1204831	Phase 1

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 Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	38 participants
Allocation:	Non-Randomized
Intervention Model:	Single Group Assignment
Masking:	None (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
Study Start Date :	April 2010
Actual Primary Completion Date :	March 2012

Arms and Interventions

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

Outcome Measures

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Primary Outcome Measures :

1. To determine the maximum tolerated dose (MTD) of EMD 1204831 in subjects with advanced solid tumors [ Time Frame: After first cycle of treatment ]

Secondary Outcome Measures :

1. 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. ]
2. 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. ]
3. 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. ]
4. 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. ]
5. 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. ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

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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

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	EMD Serono
ClinicalTrials.gov Identifier:	NCT01110083 History of Changes
Other Study ID Numbers:	EMR200096-001
First Posted:	April 26, 2010
Last Update Posted:	October 22, 2013
Last Verified:	October 2013

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

Additional relevant MeSH terms:

Neoplasms