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Study Summary
No. 2005-0751:.......Lymphoma; Phase I Studies; Solid Tumors......David S. Hong......Investigational Cancer Therapeutics
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Study Summary Title
Study Summary
Number:
2005-0751
Study Title:A Phase I/Ib, Multicenter, Open-Label, Dose Escalation Study of E7080 in Patients with Solid Tumors and in Combination with Temozolomide in Patients with Advanced and/or Metastatic Melanoma
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Physician New Patient Referral
Name:David S. HongPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Investigational Cancer TherapeuticsReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-794-1226
Contact us about clinical trials
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General Information
Disease Group:Lymphoma
Phase I Studies
Solid Tumors
Supported By:N/A
Phase of Study:Phase IReturn
Visit:
Schedules 1 and 2 /Cycles 1/2
Day(s) 1, 2, 8, 15, and 22

Schedules 1 and 2/Subsequent cycles
Day(s) 1and 15

Final Visit
28 days after the last dose of E7080

Treatment
Agents:
E7080Home Care:Daily drug administration.
Treatment Loc:Independent Multicenter Arrangements
Estimated
Length of Stay
in Houston:
N/A
Description/
Intervention:
The goals of this clinical research study are to find the best way to give
E7080, either alone or when combined with temozolomide (TMZ), and how much of
the drug and/or drug combination can be given safely to patientce with solid
tumors or melanoma. Researchers want to learn the effects, good and bad, of
E7080 when it is given by itself, as well as when it is combined with TMZ.

Researchers will also look at the effect of E7080 when combined with
Temozolomide (TMZ) in patients with advanced melanoma in the melanoma
combination group.

Participants who are already enrolled on this study will continue to receive
E7080 alone.

You will be asked to have blood drawn for pharmacodynamic (PD) and
pharmacokinetic (PK) testing (the study of what a drug does to the body). This
will help scientists to examine the effect of the drug on tumors.
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Study Objectives / Outcomes
Primary
1. To determine the maximum tolerated dose (MTD) of E7080, given as continuous bid dosing
2. To identify the dose limiting toxicities (DLT) of E7080
3. To explore the safety and tolerability of E7080
4. To determine the pharmacokinetic profile of E7080
5. To determine the MTD and the pharmacokinetic profile of E7080 when given as continuous qd dosing in combination with temozolomide
6. To explore the serum biomarkers of apoptosis
    Secondary
    1. To investigate potential biomarkers of efficacy consistent with the mechanism of action of E7080 including:
    a. Changes in vascular perfusion and permeability characteristics using DCE-MRI pre-treatment as measured by Ktrans and IAUGC(90,BN); these functional changes will also be correlated with best overall tumor response by RECIST and changes in
    CT tumor volume and CT radiodensity.

    b. Changes in serum proteins and protein expression that may be associated with anti-angiogenic activity.

    c. The effect of adding temozolomide to E7080 on serum markers of apoptosis in
    comparison with the effect of E7080 monotherapy on these biomarkers and the relationship between acute changes and steady-state changes from baseline in these biomarkers with either clinical outcome or AEs.

    2. To evaluate the safety and tolerability of the 10-mg bid dose in a cohort of 25 melanoma patients, using the standard 3+3 dose-finding scheme (hereafter referred to as the Expanded Melanoma Cohort).

    3.To evaluate the safety and tolerability of E7080 given once daily in combination with
    temozolomide (TMZ) in a cohort of up to 40 melanoma patients (hereafter referred to as the Melanoma Combination Cohort), using a standard 3+3 dose-finding scheme.
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    Study Status Information
    Study Activation / Registration Date:01/26/2007
    IRB Review and Approval Date:09/06/2006
    Study Type:Unavailable
    Recruitment Status:Open
    Projected Accrual:112
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    Enrollment Eligibility
    If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

    Inclusion Criteria:1) Patients with a histologically and/or cytologically confirmed solid tumor or lymphoma who are resistant/refractory to approved therapies or for whom no curative therapies are available (not applicable for patients in the Schedule 2 expanded melanoma cohort)

    2) All previous treatment (including surgery and radiotherapy) must have been completed at least four weeks prior to study entry and any acute toxicities must have resolved

    3) Aged >/= 18 years Because of the potential additional risk to children suggested by preclinical models of dysplasia in growing epiphyseal growth plates, enrollment will be limited to adult patients

    4) ECOG performance status score of 0 or 1

    5) Written informed consent prior to any study specific screening procedures with the understanding that the patient may withdraw consent at any time without prejudice

    6) Willing and able to comply with the protocol guidelines for the duration of the study

    7) For patients in the expanded Schedule 2 melanoma cohort only: Patients with histologically and/or cytologically confirmed advanced and/or metastatic melanoma who are resistant/refractory to approved therapies or for whom no curative therapies are available. In addition, patients must have melanoma lesions amenable to tissue biopsy and must agree to undergo biopsies of malignant and adjacent nonmalignant tissue pretreatment and at the end of Cycle 1 of treatment

    8) For patients in the Melanoma Combination Cohort only: histologically and/or cytologically confirmed melanoma that is advanced and/or metastatic

    Exclusion Criteria:1) Untreated or unstable metastases to the central nervous system (CNS) tumors. Patients who have completed local therapy and have discontinued the use of steroids for this indication at least 4 weeks prior to commencing treatment and in whom stability has been proven by at least 2 CT or MRI scans obtained at least 4 weeks apart are permitted

    2) Any of the following laboratory parameters: hemoglobin < 9 g/dL (5.6 mmol/L); neutrophils < 1.5 x 109/L; platelets < 100 x 109/L; serum bilirubin > 25 micromol/L (1.5 mg/dL); liver function tests with values > 3 x upper limit of normal (ULN); renal function with serum creatinine > 1.5 ULN or creatinine clearance < 60 mL/min

    3) Positive history of HIV, active hepatitis B or active hepatitis C or severe/uncontrolled intercurrent illness or infection

    4) Patients with centrally located non-small cell lung cancers and squamous cell lung cancers

    5) Clinically significant cardiac impairment or unstable ischemic heart disease including a myocardial infarction within six months of study start

    6) Patients with marked Baseline prolongation of QT/QTc interval (QTc interval > 450 msec for males or > 470 msec for females) using the Fridericia method for QTc analysis

    7) Bleeding or thrombotic disorders, or using therapeutic dosages of anticoagulants, Bleeding or thrombotic disorders, or using therapeutic dosages of anticoagulants, such as warfarin. Occasional use of NSAIDs and antiplatelet agents such as aspirin, clopidogrel, aggrenox and dipyridamole are not considered exclusionary if taken <7 days per 28 days. However, if the patient requires chronic use (>/=7 days out of 28 days) of full doses of aspirin or NSAIDs then the patient is excluded. Concomitant antiplatelet agents and NSAIDs should be used with caution

    8) Requirement for chronic use of full dose aspirin or non-steroidal anti-inflammatory drugs (NSAIDs)

    9) Poorly controlled hypertension (defined as requiring changes in any hypertensive regimen within three months of study entry) or patients diagnosed with hypertension based on repeat blood pressure measurements of > 160/90 mmHg at screening

    10) > 1+ proteinuria on urine dipstick testing or 30 mg/dL

    11) A history of gastrointestinal malabsorption or having undergone surgery requiring gastrointestinal anastomoses within four weeks of starting therapy or who have not recovered from major surgery within three weeks of starting therapy

    12) History of alcoholism, drug addiction, or any psychiatric or psychological condition which, in the opinion of the investigator, would impair study compliance

    13) Any treatment with investigational drugs within 30 days before the start of the study

    14) Previous treatment with E7080

    15) Known intolerance to temozolomide (or any of the excipients)

    16) Women who are pregnant or breast-feeding; women of childbearing potential with a positive pregnancy test at screening or no pregnancy test. Women of childbearing potential unless (1) surgically sterile or (2) using adequate measures of contraception (including two forms of contraception, one of which must be a barrier method) in the opinion of the Investigator. Perimenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential.

    17) Fertile males with female partners who are not willing to use contraception or whose female partners are not using adequate contraceptive protection

    18) Legal incapacity

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    Links
    Registration Number: NCT00121680
    Study Information on Clinical Trials Registry (clinicaltrials.gov)

    Other Links:
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    Results


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