RAD001 Plus Octreotide Depot in Metastatic or Unresectable Low Grade Neuroendocrine Carcinoma
Condition: Neuroendocrine Carcinoma; Islet Cell Carcinoma
MeSH terms: Carcinoma; Carcinoma, Neuroendocrine; Carcinoma, Islet Cell
Intervention: RAD001; Octreotide Depot
Intervention description: Starting dose of 5 or 10 mg by mouth daily.; 30 mg injection into the muscle of either buttock once every 28 (±7) days.
Intervention MeSH terms: Everolimus; Octreotide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 67.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Neuroendocrine Carcinoma; Low Grade Neuroendocrine Carcinoma; Neuroendocrine Carcinoid; Islet Cell Carcinoma; RAD001; Everolimus; Octreotide Depot; Sandostatin LAR; Octreotide long-acting release (LAR); Octreotide LAR

Summary:

      Objectives:

      Primary endpoint:

      -Assess the clinical activity of RAD 001 plus depot octreotide as defined by progression free
      survival (PFS) duration defined by RECIST criteria in treated and untreated patients with
      metastatic, unresectable low grade neuroendocrine carcinoma.

      Secondary endpoints:

        -  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.

        -  To determine the expression/phosphorylation status of the components of the mTOR
           signaling pathway in the primary tumors, in order to determine whether these markers can
           be used as predictors of sensitivity to the combination of RAD001 and octreotide.

        -  To determine the effect of the combination of RAD001 and octreotide on the expression
           and phosphorylation of mTOR's targets in the accessible tumor tissue, in order to
           identify potential pharmacodynamics markers of response to this drug combination.

        -  To observe the effects of treatment with RAD001 on plasma angiogenic biomarkers.
    

Eligibility 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 with neuroendocrine tumors associated with MEN1 syndrome will be eligible.

          -  Patients must have either metastatic or unresectable local-regional cancer.

          -  Patients must have measurable disease, as defined by RECIST (Response Evaluation
             Criteria In Solid Tumors).

          -  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 (Platelet Derived
             Growth Factor Receptor), VEGF (Vascular endothelial growth factor), or EGFR [epidermal
             growth factor receptor] (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
             Upper Limit of Normal (ULN), serum creatinine < 1.5 mg/dL, AST (SGOT) less/equal 2.5 x
             ULN, ALT (SGPT) less/equal 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.