The goal of this clinical research study is to learn if the combination of RAD001 and octreotide depot can shrink or slow the growth of advanced low grade neuroendocrine carcinoma that can not be removed surgically. The safety of this combination therapy will also be studied.

Condition	Intervention	Phase
Carcinoma, Neuroendocrine Carcinoid Tumor Carcinoma, Islet Cell	Drug: RAD001  Drug: octreotide depot	Phase II

Further Study Details: 

Primary Outcomes: Assess the clinical activity of RAD 001 plus depot octreotide as defined by objective response rate measured by RECIST criteria in treated and untreated patients with metastatic, unresectable low grade neuroendocrine carcinoma
Secondary Outcomes: Assess the progression free survival duration of patients with metastatic, unresectable low grade neuroendocrine carcinoma treated with RAD 001 plus depot octreotide; Assess the safety of RAD 001 plus depot octreotide in patients with metastatic, unresectable low grade neuroendocrine carcinoma
Expected Total Enrollment:  40

Low grade neuroendocrine carcinoma include carcinoid and pancreatic endocrine tumors (islet cell carcinomas). Current treatments for bulky metastatic tumors have demonstrated either limited effectiveness, unacceptable side effects, or both.

RAD001 is an orally administered cell cycle inhibitor with antitumor properties. RAD001 inhibits the mammalian target of rapamycin (mTOR), a key regulator of cell proliferation or death. TSC1/2 complex is a natural inhibitor of mTOR. It has been observed that patients with genetic abnormalities in TSC2 gene develop neuroendocrine tumors. Insulin like growth factor-1 (IGF1) and its receptor may also play a role in the growth of neuroendocrine carcinoma through activation of mTOR. Octreotide is known to suppress IGF1.

Study treatment is as follows:

RAD001 taken by mouth daily. Octreotide depot administered by intramuscular injection every 28 days.

A course of treatment consists of 28 days. Octreotide depot must be administered at M. D. Anderson Cancer Center. This will be done in the outpatient setting.

Participants will be evaluated by computerized tomography (CT) or magnetic resonance imaging (MRI) for effectiveness of therapy every 3 courses (12 weeks). Participants may remain on study for a total of 12 courses or until documentation of disease progression, whichever occurs first.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• Patients with histologic proof of low grade neuroendocrine carcinoma will be eligible. Both carcinoid (any site [atypical/intermediate grade carcinoid is allowed]) and islet cell (pancreatic endocrine tumor) will be eligible.
• Patients must have either metastatic or unresectable local-regional cancer.
• Patients must have measurable disease, as defined by RECIST.
• Prior and concurrent octreotide (Sandostatin and Sandostatin LAR) is allowed.
• Prior radiation therapy is permitted. A recovery period of at least 4 weeks after completion of radiotherapy is required prior to enrollment.
• Patients may have received 0, 1, or 2 prior cytotoxic chemotherapy.
• Chemotherapy used as a radiosensitizer will be considered one prior chemotherapy regimen.
• Patients may have received prior interferon (not counted toward prior cytotoxic chemotherapy).
• Patients may have received prior therapy targeting c-kit, abl, PDGFR, VEGF, or EGFR (not counted toward prior cytotoxic chemotherapy).
• Patients may have had prior hepatic artery embolization. There must be residual measurable disease. Chemoembolization will be considered as one prior chemotherapy regimen.
• Patients must have a performance status of 0, 1, or 2 (Zubrod scale).
• Patients must be >/= 18 years old (age limit due to lack of adequate safety data in younger patients).
• Patients must give written informed consent.
• Patients should have adequate organ function defined as follows: Absolute granulocytes > 1,500/mm3, hemoglobin > 8 g/dl, and platelets > 100,000/mm3. Serum bilirubin < 1.5 x ULN, serum creatinine < 1.5 mg/dL, AST (SGOT) <= 2.5 x ULN, ALT (SGPT) <= 2.5 x ULN.
• Patients must have recovered from recent surgery. One week must have elapsed from the time of a minor surgery and 4 weeks from major surgery.
• Fertile patients, both male and female, must practice contraception during treatment.

Exclusion Criteria:

• Patients may receive no other concurrent chemotherapy, immunotherapy, or radiotherapy.
• Patients with intolerance to octreotide.
• Patients who have received chemotherapy, immunotherapy, or investigational therapy in the 30 days prior to registration.
• Patients with uncontrolled diabetes mellitus as defined by fasting blood sugar > 1.5 x ULN.
• Pregnant or lactating women. All women of child-bearing potential must have a negative pregnancy test prior to entry into the study. All patients of child-bearing potential must be advised of the importance of avoiding pregnancy and using appropriate methods of contraception while participating in this investigational trial. Women who have had menses within the past 2 years, who have not had a tubal ligation, or bilateral oophorectomy are considered to be of child-bearing potential. Appropriate methods of contraception include hormonal or barrier method of birth control; abstinence.
• Serious intercurrent infections, or nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this therapy.
• Psychiatric disorders rendering them incapable of complying with the requirements of the protocol.
• Osseous metastasis as only site of disease.
• Any concurrent active malignancy other than non-melanoma skin cancers or carcinoma-in-situ of the cervix. Patients with previous malignancies but without evidence of disease for > 5 years will be allowed to enter the trial.

Please refer to this study by ClinicalTrials.gov identifier  NCT00113360

Texas
      The University of Texas M. D. Anderson Cancer Center, Houston,  Texas,  77030,  United States; Recruiting

Study chairs or principal investigators

James Yao, M.D.,  Study Chair,  M.D. Anderson Cancer Center   

Study ID Numbers:  2004-0597
Record last reviewed:  June 2005
Last Updated:  June 30, 2005
Record first received:  June 7, 2005
ClinicalTrials.gov Identifier:  NCT00113360
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-07-05