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Study Summary
No. 2005-0683:.......Advanced Cancers; Solid Tumors......Jaffer Ajani......Gastrointestinal Medical Oncology
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Study Summary Title
Study Summary
Number:
2005-0683
Study Title:A Phase I, Dose-escalation, Sequential-cohort Study of the Safety, Tolerability, and Pharmacokinetics of Intravenous AVE0005 (VEGF Trap) in Combination with Intravenous Docetaxel/Cisplatin/5-Fluorouracil Administered Every 3 Weeks In Subjects with Advanced Solid Malignancies
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Physician New Patient Referral
Name:Jaffer AjaniPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Gastrointestinal Medical OncologyReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-792-2828
Contact us about clinical trials
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General Information
Disease Group:Advanced Cancers
Solid Tumors
Supported By:N/A
Phase of Study:Phase IReturn
Visit:
2-3 times a month
Treatment
Agents:
5-Fluorouracil
AVE0005
Cisplatin
Docetaxel
Home Care:none
Treatment Loc:Independent Multicenter Arrangements
Estimated
Length of Stay
in Houston:
none
Description/
Intervention:
The goal of this clinical research study is to look at the highest tolerated
dose of AVE0005 (VEGF Trap) that can be combined with docetaxel, cisplatin, and
5-fluorouracil (called "DCF") in advanced cancer patients. Researchers will
study how the body handles these drugs, and whether or not the body makes
antibodies against AVE0005 (VEGF Trap). This information will be used to find
the highest tolerated dose of AVE0005 (VEGF Trap), which will be used in a
Phase II study. Tumor response and safety will also be studied.
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Study Objectives / Outcomes
The primary objective of the study is:
    1. To determine dose-limiting toxicity (DLT) and recommended Phase II dose (RPTD) of AVE0005 (Vascular Endothelial Growth Factor [VEGF] Trap) administered intravenously (IV) in combination with intravenous DCF (docetaxel, cisplatin, 5-FU) chemotherapy, in subjects with advanced solid malignancies.

Secondary Objective
    1. To assess the safety profile of IV AVE0005 (VEGF Trap) when administered in combination with intravenous DCF chemotherapy.
    2. To determine the pharmacokinetics of IV AVE0005 (VEGF Trap) and docetaxel, cisplatin, 5-FU, when administered in combination.
    3. To make a preliminary assessment of antitumor effects of the combination of DCF plus AVE0005 (VEGF Trap).
    4. To evaluate the immunogenicity of IV AVE0005 (VEGF Trap).
    5. To explore potential biological and pharmacogenomic markers of AVE0005 (VEGF Trap) activity.
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Study Status Information
Study Activation / Registration Date:04/18/2006
IRB Review and Approval Date:10/05/2005
Study Type:Therapeutic
Recruitment Status:Terminated
Projected Accrual:45
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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) Histologically or cytologically confirmed solid malignancy that is metastatic or unresectable, and for which standard curative measures do not exist, but for which DCF treatment is appropriate.

2) Eighteen years of age or older.

3) ECOG performance status </= 1.

4) Resolution of any toxic effects of prior therapy (except alopecia) to NCI CTCAE v.3.0 grade </= 1 and to baseline laboratory values as defined in inclusion criterion #5.

5) Adequate organ and bone marrow function as evidenced by: a. hemoglobin >/= 9.0 g/dL b. absolute neutrophil count >= 1.5 x 10^9/L c. platelet count>/= 100 x 10^9/L d. creatinine </= 1.5 x ULN (if creatinine 1.0 – 1.5 x ULN, then calculated creatinine clearance according to the Cockroft-Gault formula >/= 60 mL/min), and either proteinuria </= 500 mg/24 hours or UPCR </=1 e. AST/SGOT and ALT/SGPT </=2.5 x ULN f. total bilirubin </=1.0 x ULN

6) Female subjects must be postmenopausal, surgically sterile, or using effective contraception. All female subjects of childbearing potential must have a negative pregnancy test (serum or urine) within 7 days prior to enrollment.

7) Subjects must agree to sign and date an Institutional Review Board (IRB)-approved subject informed consent form. This informed consent must be obtained in writing for all subjects at enrollment into the study.

8) Subjects must be willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

Exclusion Criteria:1) Diagnosis of squamous-cell lung cancer.

2) Anticipation of need for a major surgical procedure or radiation therapy during the study.

3) Likelihood of requiring treatment during the study period with drugs not permitted by the clinical study protocol.

4) Prior cumulative cisplatin chemotherapy dose exceeding 300 mg/m^2.

5) History of hypersensitivity to any Trap agents, recombinant proteins, taxanes, platinum compounds, fluoropyrimidines, or polysorbate 80.

6) Known dihydropyrimidine dehydrogenase deficiency.

7) Treatment with chemotherapy, hormonal therapy, radiotherapy, surgery, blood products, or an investigational agent within 3 weeks (6 weeks for nitrosoureas, mitomycin C, immunotherapy, cytokine therapy, or major surgery) of study enrollment.

8) Cumulative radiation therapy to >25% of the total bone marrow.

9) Uncontrolled hypertension, defined as blood pressure >140/90 mm Hg (NCI CTCAE v.3.0 grade >/=2), or systolic blood pressure >160 mm Hg if diastolic blood pressure <90 mm Hg, on at least 2 repeated determinations on separate days within 3 months prior to study enrollment.

10) Any of the following within 6 months prior to study enrollment: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, NYHA class III or IV congestive heart failure, cerebrovascular accident or transient ischemic attack, grade >/=2 peripheral neuropathy, peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis, pulmonary embolism, deep vein thrombosis, or other thromboembolic event.

11) History of brain metastases, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease on screening CT or MRI scan.

12) Evidence of clinically significant bleeding diathesis or underlying coagulopathy.

13) Active infection, or on antiretroviral therapy for HIV disease.

14) Subject is the investigator or any subinvestigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol.

15) Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study.

16) Subject unlikely to comply with protocol, e.g., uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study.

17) Pregnancy or breastfeeding.

18) Other severe acute or chronic medical or psychiatric condition, or significant laboratory abnormality requiring further investigation that may cause undue risk for the subject's safety, inhibit protocol participation, or interfere with interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study.

19) Subjects who have previously been treated with the investigational product. Prior treatment with docetaxel, cisplatin, or 5-fluorouracil, however, may be permitted.

20) A subject may not be enrolled in this study more than once

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Links
Registration Number: NCT00104923
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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