A Dose Escalation Study of E7107 Administered Intravenously on Days 1 and 8 Every 21 Days to Patients With Solid Tumors

NCT00499499 | Suspended Phase 1

• 1 other identifier: E7107-A001-101
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to investigate E7107 in patients with solid tumors. This is an open label, dose-escalation study of E7107. The maximum tolerated dose (MTD) of the single agent will be established by determining the occurrence of dose limiting toxicities during the first three weeks of therapy (Cycle 1). Patients in this study will be treated at multiple dose levels, starting at 0.6 mg/m\^2. Patients will receive E7107 as a 30-minute intravenous infusion on Days 1 and 8 every 21 Days.

Conditions

Cancer

Keywords

Cancer; solid tumors

Outcome Measures

Primary Outcomes (1)

• Tumor assessments should be performed at screening and then every 2 cycles. A best response according to RECIST (Response Evaluation Criteria in Solid Tumors) will be documented by the investigator for each patient.

  Every 6 weeks

Secondary Outcomes (1)

• Clinical examination (either full or symptom-directed), adverse event reporting, laboratory screens, and electrocardiograms (ECGs) will be performed at every visit.

  Every 21 days

Study Arms (1)

1

EXPERIMENTAL

Drug: E7107

Interventions

E7107 DRUG

E7107 will be administered as an intravenous infusion over 30 minutes at a starting dose of 0.6 mg/m\^2 to the first cohort of patients. The same dose will be given on Days 1 and 8 of a 21-day cycle. Dose escalation will not occur until the maximum tolerated dose is reached. The selection of subsequent dose levels will be performed according to an accelerated design.

1

Eligibility Criteria

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

You may qualify if:

• Patients with histologically and/or cytologically confirmed solid tumors who have progressed after receiving approved therapies for their disease and for whom no effective therapies are available.
• Surgery and radiotherapy must have been completed at least four weeks prior to study entry, and prior chemotherapy and other anti-cancer therapy, excluding bisphosphonates at a steady dose level, must have been discontinued 2 to 3 weeks previously. All acute toxicities related to these treatments must have resolved.
• Aged ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• Written informed consent prior to any study specific screening procedures, which will include mandatory consent to provide a blood sample specifically for pharmacogenomic analysis, with the understanding that the patient may withdraw consent at any time without prejudice. Tumor biopsy for pharmacogenomic (PG) analysis will be voluntary.
• Willing and able to comply with the protocol for the duration of the study.
• Anticipated life expectancy \> three months.

You may not qualify if:

• Patients with the following characteristics will not be eligible for the study.
• Symptomatic or progressive brain tumors or brain or leptomeningeal (CNS) metastases requiring clinical intervention, except if they have completed local therapy and have discontinued the use of corticosteroids for this indication for at least two weeks before starting treatment with E7107.
• Any of the following laboratory parameters:
• hemoglobin \< 9 g/dL (5.6 mM)
• neutrophils \< 1.5 x 10\^9/L
• platelets \< 100 x 10\^9/L
• serum bilirubin \> 25 μM (1.5 mg/dL)
• liver function tests (defined as AST and ALT) with values \> 3 x ULN (5 x ULN if liver metastases are present)
• serum creatinine \> 1.5 x ULN or creatinine clearance \< 40 mL/min.
• Positive history of HIV, active hepatitis B or active hepatitis C or severe/uncontrolled intercurrent illness or infection.
• Clinically significant cardiac impairment or unstable ischemic heart disease (greater than Class II according to New York Heart Association (NYHA) classification) including a myocardial infarction within six months of study start.
• Bleeding or thrombotic disorders, or using therapeutic dosages of anticoagulants
• History of alcoholism, drug addiction, or any psychiatric or psychological condition which, in the opinion of the Investigator, would impair study compliance.
• Women who are pregnant or breast-feeding. Women of childbearing potential with either a positive serum pregnancy test at screening, a positive urine pregnancy test at the beginning of any cycle, or no pregnancy test. Women of childbearing potential unless using two forms of contraception, one of which must be a barrier method. Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential.
• Fertile men and fertile women who are not willing to use contraception, or fertile men or fertile women with a partner who is not willing to use contraception

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (2)

Karmanos Cancer Center

Detroit, Michigan, United States

Location

M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Hong DS, Kurzrock R, Naing A, Wheler JJ, Falchook GS, Schiffman JS, Faulkner N, Pilat MJ, O'Brien J, LoRusso P. A phase I, open-label, single-arm, dose-escalation study of E7107, a precursor messenger ribonucleic acid (pre-mRNA) splicesome inhibitor administered intravenously on days 1 and 8 every 21 days to patients with solid tumors. Invest New Drugs. 2014 Jun;32(3):436-44. doi: 10.1007/s10637-013-0046-5. Epub 2013 Nov 22.

  PMID: 24258465 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

E 7107

Study Officials

• Ewa Matczak

  Eisai Inc.

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: July 9, 2007
• First Posted: July 11, 2007
• Study Start: July 1, 2007
• Primary Completion: June 1, 2009
• Study Completion: August 1, 2010
• Last Updated: February 4, 2009

Record last verified: 2009-02

Locations

US (2)