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

NCT01110083 | Terminated Phase 1

• 1 other identifier: EMR200096-001
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

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.

Conditions

Solid Tumors

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

Outcome Measures

Primary Outcomes (1)

• To determine the maximum tolerated dose (MTD) of EMD 1204831 in subjects with advanced solid tumors

  After first cycle of treatment

Secondary Outcomes (5)

• 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.

Study Arms (1)

Arm 1

EXPERIMENTAL

Drug: EMD 1204831

Interventions

EMD 1204831 DRUG

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

Arm 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• EMD Serono: lead

Study Sites (1)

M.D. Anderson Cancer Center

Houston, Texas, United States

Location

MeSH Terms

Interventions

4-(2-(2-(3-(3-(1-methyl-1H-pyrazol-4-yl)-6-oxo-1,6-dihydropyridazin-1-ylmethyl)phenyl)pyrimidin-5-yloxy)ethyl)morpholine

Study Officials

• Manfred Klevasath, MD

  Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 19, 2010
• First Posted: April 26, 2010
• Study Start: April 1, 2010
• Primary Completion: March 1, 2012
• Last Updated: October 22, 2013

Record last verified: 2013-10

Locations

US (1)