MDACC Study Summary 2006-0953

Study Summary
No. 2006-0953:.......Endocrine; Gastrointestinal......James Yao......Gastrointestinal Medical Oncology

Study Summary Title



Study Summary Number:	2006-0953

Study Title:	A randomized, double-blind, placebo-controlled, multicenter phase III study in patients with advanced carcinoid tumor receiving Sandostatin LARŽ Depot and RAD001 10 mg/d or Sandostatin LARŽ Depot and placebo (CRAD001C2325)

Physician

New Patient Referral



Name:	James Yao	Patients Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Dept:	Gastrointestinal Medical Oncology	Referring 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

General Information



Disease Group:	Endocrine Gastrointestinal	Supported By:	Novartis

Phase of Study:	Phase III	Return Visit:	For cycle 1, Days 1 and 15. Every 28 days starting on cycle 2 (Cycle is 28 days)

Treatment Agents:	RAD001 Sandostatin LAR Depot	Home Care:	RAD001 or matching placebo for self-administration at home.

Treatment Loc:	Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions

Estimated Length of Stay in Houston:	NA


Description/ Intervention:	The goal of this clinical research study is to learn if RAD001 (also called Everolimus) can help control advanced carcinoid tumors. The safety of this drug will also be studied.

Study Objectives / Outcomes

Primary objective
To determine whether treatment with RAD001(everolimus) 10 mg/d plus Sandostatin LARŽ Depot prolongs the progression free survival (PFS) compared to treatment with Sandostatin LARŽ Depot alone in patients with advanced carcinoid tumor

Secondary objectives
1) To evaluate the anti-tumor effect of RAD001 on other tumor endpoints [best overall response rate - Complete Response (CR) and Partial Response (PR), response duration]
2) To compare overall survival (OS) between the study arms
3) To compare changes from baseline in 5-hydroxyindoleacetic acid (5-HIAA) and chromogranin A (CgA)
4) To determine the safety and tolerability of the combination of RAD001 (10 mg/d) plus Sandostatin LARŽ Depot
5) To characterize the pharmacokinetics of RAD001 and Sandostatin LARŽ Depot administered in combination in carcinoid indications

Exploratory objectives
1) To determine the effects of RAD001 on plasma angiogenic molecules such as VEGF and basic FGF
2) To characterize pre-treatment tumor samples by immunohistochemical and genetic analyses indicating activation of the mTOR pathway
3) To assess the relationship between RAD001 steady state levels, tumor response, and Chromogranin A response (50% decrease)

Study Status Information



Study Activation / Registration Date:	09/05/2007

IRB Review and Approval Date:	03/22/2007

Study Type:	Phase Iii

Recruitment Status:	Closed

Projected Accrual:	390

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) Advanced (unresectable or metastatic) biopsy-proven carcinoid tumor.

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.

4) Measurable disease per RECIST determined by Triphasic Computer Tomography (CT) scan or MRI.

5) Patients must have a history of secretory symptoms, which is defined as symptoms of diarrhea or flushing or both which were attributed to their carcinoid tumor. However, these symptoms need not be active at the time of enrollment.

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

7) Adequate liver function as shown by: serum bilirubin </= 1.5 x ULN; INR < 1.3 (or < 3 on anticoagulants); ALT and AST </= 2.5x ULN (</= 5x ULN in patients with liver metastases).

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

9) 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.

10) Performance Status 0-2 on the WHO scale.

11) Adult male or female patients > or = 18 years of age.

12) Women of childbearing potential must have had a negative serum or urine pregnancy test within 48 hours prior to the administration of the first study treatment.

13) Patients who give a written informed consent obtained according 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) Received treatment with Sandostatin LARŽ Depot or any other long-acting somatostatin analog within 2 weeks prior to randomization.

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

5) Prior therapy with mTOR inhibitors (sirolimus, temsirolimus, everolimus).

6) Known intolerance or hypersensitivity to octreotide, Sandostatin LAR, RAD001 (everolimus) or other rapamycins (sirolimus, temsirolimus).

7) Uncontrolled diabetes mellitus as defined by fasting serum glucose >1.5 X ULN.

8) 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.

9) Patients receiving chronic treatment with corticosteroids or another immunosuppressive agent.

10) Patients with a known history of HIV seropositivity.

11) Patients who have a history of another primary malignancy </= 3 years, with the exceptions of non-melanoma skin cancer, and carcinoma in situ of uterine cervix.

12) 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.

13) Patients who have received an investigative drug or therapy within the last 30 days.

Links

Registration Number: NCT00412061
Study Information on Clinical Trials Registry (clinicaltrials.gov)