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Study Summary
No. 2007-0504:.......Endocrine......James Yao......Gastrointestinal Medical Oncology
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Study Summary Title
Study Summary
Number:
2007-0504
Study Title:A Randomized Double-Blind Phase III Study of RAD001 10 mg/d plus Best Supportive Care Versus Placebo plus Best Supportive Care in the Treatment of Patients with Advanced Pancreatic Neuroendocrine Tumor (NET) [CRAD001C2324]
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Physician New Patient Referral
Name:James YaoPatients 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:EndocrineSupported By:Novartis
Phase of Study:Phase IIIReturn
Visit:
Patients will return to MDACC on days 1 and 15 in cycle 1, and then on day 1 of
every cycle thereafter.
Treatment
Agents:
RAD001Home Care:There will not be home care for this study.
Treatment Loc:Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions
Estimated
Length of Stay
in Houston:
Patients will not be hospitalized for this protocol
Description/
Intervention:
The goal of this clinical research study is to learn if RAD001 can slow the
growth of advanced pancreatic neuroendocrine tumors. The safety of the drug
will also be studied.
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Study Objectives / Outcomes
Primary objectives
    To determine whether treatment with RAD001 (everolimus) 10 mg/d plus best supportive care prolongs the progression free survival (PFS) compared to treatment with placebo plus best supportive care in patients with advanced pancreatic neuroendocrine tumor (NET).

Secondary objectives
    • To evaluate the effect of RAD001 on other tumor endpoints: objective response rate - complete response (CR) partial response (PR), response duration
    • To compare overall survival (OS) between the study arms
    • To determine the safety and tolerability of RAD001 (10 mg/d) in patients with advanced pancreatic NET
    • To characterize the pharmacokinetics of RAD001 in pancreatic NET indications
    • To compare changes from baseline in chromogranin A (CgA) and follow other biochemical tumor markers produced by the tumor that are elevated at baseline, during subsequent visits. e.g., neuron specific enolase, pancreatic polypeptide, gastrin, glucagon, and VIP. Insulin, pro insulin, and c-peptide in patients with insulinomas
    • To characterize pre-treatment tumor samples by immunohistochemical and genetic analyses indicating activation of the mTOR pathway
    • To assess the relationship between RAD001 steady state levels, tumor response, and chromogranin A response (50% decrease from baseline)
    • To determine the effects of RAD001 on plasma antigenic molecules e.g. VEGF, basic FGF, PLGF, sVEGFR1, and sVEGFR2
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Study Status Information
Study Activation / Registration Date:12/03/2007
IRB Review and Approval Date:12/03/2007
Study Type:Phase Iii
Recruitment Status:Closed
Projected Accrual:392
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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 advanced (unresectable or metastatic) biopsy-proven pancreatic NET

2) Patients must have confirmed low-grade or intermediate-grade neuroendocrine carcinoma

3) Patients must have radiological documentation of progression of disease within 12 months prior to randomization. If patient received anti-tumor therapy during the past 12 months, he/she must have radiological documentation of progression of disease while on or after receiving the therapy

4) Measurable disease per RECIST criteria using Triphasic Computed Tomography (CT) scan or multiphase MRI for radiologic assessment

5) Adequate bone marrow function as shown by: ANC >/= 1.5 x 10^9/L, Platelets >/= 100 x 10^9/L, Hemoglobin >9 g/dL

6) Adequate liver function as shown by: Serum bilirubin </= 1.5 x ULN; INR < 1.3 (INR < 3 in patients treated with anticoagulants); ALT and AST </= 2.5 x ULN (</= 5x ULN in patients with liver metastases)

7) Adequate renal function: serum creatinine </= 1.5 x ULN

8) Fasting serum cholesterol </= 300 mg/dL OR </= 7.75 mmol/L AND fasting triglycerides </= 2.5 x ULN. NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication

9) Performance Status 0-2 on the WHO scale

10) Adult male or female patients >/= 18 years of age

11) Women of childbearing potential must have a negative serum pregnancy test within 14 days of enrollment and /or urine pregnancy test 48 hours prior to the administration of the first study treatment

12) Written informed consent from patients must be obtained in accordance to local guidelines

Exclusion Criteria:1) Patients with poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid, goblet cell carcinoid and small cell carcinoma are not eligible

2) Cytotoxic chemotherapy, immunotherapy or radiotherapy within 4 weeks prior to randomization

3) Hepatic artery embolization within the last 6 months (1 month if there are other sites of measurable disease), or cryoablation/ radiofrequency ablation of hepatic metastasis within 2 months of enrollment

4) Prior therapy with mTOR inhibitors (sirolimus, temsirolimus, everolimus)

5) Uncontrolled diabetes mellitus as defined by fasting serum glucose > 1.5 x ULN

6) Patients who have any severe and/or uncontrolled medical conditions such as: unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction </= 6 months prior to randomization, serious uncontrolled cardiac arrhythmia; active or uncontrolled severe infection; cirrhosis, chronic active hepatitis or chronic persistent hepatitis; severely impaired lung function (spirometry and DLCO 50% or less of normal and O2 saturation 88% or less at rest on room air).; active, bleeding diathesis

7) Patients receiving chronic treatment with corticosteroids or another immunosuppressive agent

8) Patients with a known history of HIV seropositivity

9) No other prior or concurrent malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, or other adequately treated in situ cancer, or any other cancer from which the patient has been disease free for >/= 3 years

10) Female patients who are pregnant or nursing (lactating), or adults of reproductive potential who are not using effective birth control methods. If barrier contraceptives are being used, these must be continued throughout the trial by both sexes

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Links
Registration Number: NCT00510068
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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