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Study Summary
No. 2006-0329:.......Fallopian Tube; Ovary; Peritoneum......Robert Coleman......Gynecologic Oncology
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Study Summary Title
Study Summary
Number:
2006-0329
Study Title:Phase I/II and Pharmacokinetic Study of Docetaxel plus VEGF Trap (AVE0005, NSC# 724770) in Patients with Recurrent Ovarian, Primary Peritoneal, and Fallopian Tube Cancer
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Physician New Patient Referral
Name:Robert ColemanPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Gynecologic OncologyReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-563-6719
Contact us about clinical trials
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General Information
Disease Group:Fallopian Tube
Ovary
Peritoneum
Supported By:N/A
Phase of Study:Phase I/Phase IIReturn
Visit:
Every 3 weeks. In the absence of delays due to adverse events, treatment may
continue indefinitely. If a pt has a CR as defined in the protocol, treatment
will continue for 2 additional cycles past normalization of biomarkers &
disease resolution.
Treatment
Agents:
Docetaxel
VEGF-Trap
Home Care:none
Treatment Loc:Independent Multicenter Arrangements
Estimated
Length of Stay
in Houston:
n/a
Description/
Intervention:
The goal of this clinical research study is to find the highest tolerable dose
of VEGF Trap that can be given with the drug docetaxel to patients with
ovarian, primary peritoneal (abdominal), or Fallopian tube cancer. Researchers
also hope to find out if giving these drugs together will help shrink or slow
the growth of tumors in patients who have cancer that either had gone away and
then came back after treatment or has remained after treatment. The safety of
these drugs will be studied. Researchers will study the levels of VEGF Trap in
the blood at different times and how quickly it is cleared from your body. This
is called pharmacokinetic (PK) testing. Researchers will also measure the
effect of VEGF Trap on certain blood cells called mononuclear cells.
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Study Objectives / Outcomes
Phase I - Closed to patient accrual 3/14/2008
Primary Objectives:
To determine the safety and tolerability of VEGF Trap in combination with docetaxel.

To determine the maximal tolerated dose (MTD) or maximal administered dose (MAD) of VEGF Trap given by i.v. infusion. Once the MTD or MAD has been established, a Phase II trial will be undertaken. The objectives of this phase will be to determine the response rate (in patients with measurable disease who are in the Phase II cohort).

To determine:
    The pharmacokinetics of VEGF Trap alone and in combination with docetaxel.
    The effects of VEGF Trap on tumor perfusion and metabolism (by non-invasive imaging).
    The effect treatment with VEGF Trap and docetaxel on surrogate markers (circulating endothelial precursors and circulating endothelial cells).
Phase II - Open to patient accrual 5/9/2008
Primary endpoint:
The primary endpoint of the Phase II expansion is the frequency of clinical response (partial or complete response)
To determine the progression-free and overall survival of combination VEGF Trap and Docetaxel in the Phase II population.

Secondary endpoints:
    Duration of progression-free survival and overall survival.
    Frequency and severity of adverse effects as assessed by CTCAE, v3.0
    Proportion of patients progression-free at 6 months
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Study Status Information
Study Activation / Registration Date:01/18/2007
IRB Review and Approval Date:09/20/2006
Study Type:Phase Ii Or Phase I/Ii
Recruitment Status:Closed
Projected Accrual:52 (46 evaluable*)
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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 must have recurrent or persistent epithelial ovarian, primary peritoneal or fallopian tube carcinoma. Histologic confirmation of the original primary tumor is required.

2) Because no dosing or adverse event data are currently available on the use of VEGF Trap in combination with docetaxel in patients < 18 years of age, children are excluded from this study, but will be eligible for future pediatric phase 1 combination trials.

3) Zubrod performance status </= 2. Patients who have received two prior regimens must have a performance status of 0 or 1. All taxane and/or platinum regimens are counted separately.

4) Pts must have measurable disease. Measurable disease is defined as at least 1 lesion that can be accurately measured in at least 1 dimension (longest dimension to be recorded). In the Phase I cohort, each lesion must be >/= 20mm when measured by palpation, plain x-ray, CT, or MRI or spiral CT. Pt must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST. ).

5) All patients must have measurable disease. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded). In the Expansion Cohort, each lesion must be >/= 20mm when measured by palpation, plain x-ray, CT, or MRI or >/= 10mm when measured by spiral CT scan. Patient must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST. Tumors within a previously irradiated field will be designated as "non-target" lesions.

6) Resolution of any effects of prior therapy (except alopecia) to NCI CTCAE v.3.0 grade </= 1 and to baseline laboratory values as defined in inclusion criteria numbered 6-8 below.

7) Patients must have adequate: - Bone marrow function: HGB >/= 9 g/dL, WBC >/=3,000/mcL, ANC >/=1,500/mcL - PLT >/=100,000/mcL - Hepatic function: Total bilirubin within normal institutional limits, SGOT and SGPT < 2.5 X institutional ULN - Renal function: Creatinine < 1.5 x ULN or creatinine clearance > 60ml/min according to Cockroft-Gault formula. - Neurologic function: Neuropathy (sensory and motor) </= CTCAE grade 1.

8) Patients must have adequate: Blood coagulation parameters: PT such that international normalized ratio (INR) is < 1.5 (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin or low molecular weight heparin) and a PTT < 1.2 times control.

9) Patients must have a urine protein-to-creatinine ratio (UPCR) < 1. UPCR correlates directly with the amt of protein excreted in a 24-hr urine collection. A UPCR of 1 is equal to 1 gram of protein in a 24-hr urine collection. Get 4 ml of a random urine sample in a sterile container (does not have to be a 24 hour urine). Send the sample to the lab with a separate requests for urine protein & creatinine levels. The lab will measure protein concentration (mg/dL) and creatinine concentration (mg/dL). The UPCR is derived as: protein concentration (mg/dL) / creatinine concentration (mg/dL).

10) Patients should be free of active infection requiring antibiotics.

11) Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration. Continuation of hormone replacement therapy is permitted.

12) Any other prior therapy directed at the malignant tumor, including immunologic agents, must be discontinued at least four weeks prior to registration (6 weeks for nitrosoureas or mitomycin C).

13) Patients must have had one prior platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin, or another organoplatinum compound. This initial treatment may have included high-dose therapy, consolidation, or extended therapy administered after surgical or non-surgical assessment.

14) Patients are allowed to receive, but are not required to receive, one additional cytotoxic regimen for management of recurrent or persistent disease according to the following definition: Cytotoxic regimens include any agent that targets the genetic and/or mitotic apparatus of dividing cells, resulting in dose-limiting toxicity to the bone marrow and/or gastrointestinal mucosa.

15) Patients previously treated with paclitaxel (regardless of response) are eligible for this trial.

16) Patients who previously received docetaxel for primary or recurrent disease are eligible if they did not progress on therapy or relapse within 3 months of completing therapy. Patients with persistent disease at the completion of primary therapy with docetaxel are not eligible.

17) Patients must have signed an approved informed consent.

Exclusion Criteria:1) Patients may not be receiving any other investigational agents.

2) History of allergic reactions attributed to compounds of similar chemical or biologic composition to VEGF Trap, MagnevistTM , or FDG.

3) History of allergic reaction to paclitaxel or docetaxel or with products mixed in Cremephor EL or Tween 80®.

4) Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as a known bleeding disorder, coagulopathy, peptic ulcer disease, diverticulitis, or tumor involving major vessels.

5) Patients with active and/or untreated diagnosis of pulmonary embolism, deep vein thrombosis, or other thromboembolic event (i.e. any condition felt to be associated with aberrant clotting or migration of an induced clot).

6) Patients with history or evidence upon physical examination of CNS disease, including primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within 6 months of registration on this study.

7) Patients with clinically significant cardiovascular disease including: Uncontrolled hypertension (systolic >140mm Hg or diastolic >90 mm Hg); systolic blood pressure >180 mm Hg if diastolic blood pressure is less than 90 mm Hg, or diastolic blood pressure is greater than 90 mm Hg on at least 2 repeated determinations on separate days within 3 months prior to study enrollment.

8) Patients with myocardial infarction, coronary/peripheral artery bypass graft, or unstable angina within 6 months prior to registration; New York Heart Association (NYHA) Grade III or greater congestive heart failure; Serious cardiac arrhythmia requiring medication; Grade II or greater peripheral vascular disease.

9) Patients with clinically significant peripheral artery disease, e.g., those with claudication, within 6 months of registration on this study.

10) Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies.

11) Patients whose circumstances do not permit completion of the study or the required follow-up.

12) Patients who are ineligible to undergo an MRI scan for reasons such as claustrophobia or the presence of implanted devices or metallic foreign bodies that are not MR compatible, such as ferromagnetic implants or pacers or with a known history of allergic reaction to gadolinium contrast agents.

13) Patients who are pregnant or nursing. No fetal studies in animals or humans have been performed. The possibility of harm to a fetus is likely. VEGF Trap specifically inhibits VEGF, which is responsible for formation of new blood vessels during development and antibodies can cross the placenta. It is not known whether VEGF Trap is excreted in human milk therefore VEGF Trap should not be administered to nursing women. Women of childbearing potential must agree to use contraceptive measures during study therapy and for at least 6 months after completion of VEGF Trap therapy.

14) HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with VEGF Trap. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy.

15) Patients who have a major surgical procedure, open biopsy, dental extractions or other dental surgery/procedure that results in an open wound, or significant traumatic injury within 28 days prior to the first date of treatment on this study, or anticipation of need for major surgical procedure during the course of the study; patients with placement of vascular access device or core biopsy within 7 days prior to registration.

16) Patients with other invasive malignancies, with the exception of non-melanoma skin cancer, who had (or have) any evidence of other cancer present within the last 5 years or whose previous cancer treatment contraindicates this protocol therapy.

17) Patients who have received prior therapy with VEGF Trap.

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Links
Registration Number: NCT00436501
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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