Temsirolimus in Treating Patients With Metastatic Neuroendocrine Carcinoma
Condition: Metastatic Gastrointestinal Carcinoid Tumor; Pulmonary Carcinoid Tumor; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Islet Cell Carcinoma
MeSH terms: Carcinoma; Carcinoid Tumor; Carcinoma, Neuroendocrine; Malignant Carcinoid Syndrome; Gastrointestinal Neoplasms; Carcinoma, Islet Cell; Recurrence
Intervention: temsirolimus; laboratory biomarker analysis
Intervention description: Given IV; Correlative studies
Intervention MeSH terms: Sirolimus; Temsirolimus; MTOR Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 36.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well CCI-779 works in treating patients with progressive
      metastatic neuroendocrine tumors. Drugs used in chemotherapy, such as CCI-779, work in
      different ways to stop tumor cells from dividing so they stop growing or die.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed neuroendocrine tumours
             either of carcinoid histology or a carcinoma of pancreatic islet cell origin; small
             cell variant, endocrine organ carcinomas, and adrenal gland malignancies (including
             paragangliomas) are excluded from this study

          -  Patients must have progressive metastatic disease defined by one of the following
             occurring within 6 months of study entry:

               -  At least a 25% increase in radiologically or clinically measurable disease

               -  Appearance of any new lesion or

               -  Deterioration in clinical status

          -  Patients must have measurable disease, defined as at least one lesion that can be
             accurately measured in at least one dimension (longest diameter to be recorded) as >=
             20 mm with conventional techniques or as >= 10 mm with spiral CT scan

          -  Previous local therapy (e.g. chemoembolization or bland embolization) allowed if
             completed > 6 weeks prior to study entry; for patients who received local therapy
             prior to study entry, there must be either progression of measurable disease
             documented within the treatment field, or must have measurable disease outside the
             treatment field prior to study entry

          -  Previous chemotherapy, investigational agents or radioactive therapies (e.g.
             radioactive octreotide) allowed if completed > 4 weeks prior to study entry (> 6 weeks
             if last regimen contained BCNU or mitomycin C); for patients who received systemic
             therapy prior to study entry, there must be documented progression of measurable
             disease prior to study entry

          -  Patients must not have disease that is currently amenable to surgery; prior surgery is
             allowed no less than 6 weeks prior to study entry

          -  Previous radiation therapy is allowed if > 4 weeks have elapsed since delivery of a
             dose likely to have myelotoxic effects (e.g. ≥ 3000cGy to fields including substantial
             marrow)

          -  Life expectancy of greater than 3 months

          -  ECOG performance status ≤ 2 (Karnofsky ≥ 60%)

          -  Leukocytes ≥ 3.0 x 10^9/L

          -  Absolute neutrophil count ≥ 1.5 x 10^9/L

          -  Platelets >= 100 x 10^9/L

          -  Total bilirubin ≤ 1.25 x ULN

          -  AST(SGOT)/ALT(SGPT) ≤ 3 x ULN; < 5 x ULN with liver metastases

          -  Creatinine ≤ 1.5 x ULN OR creatinine clearance (CrCl) calculated ≥ 60mL/min/1.73m^2

          -  Fasting serum cholesterol =< 350 mg/dL (9.0 mmol/L)

          -  Triglycerides =< 400 mg/dL (4.56 mmol/L)

          -  Must be willing and able to undergo tumor biopsy once before and once during
             experimental therapy; patients must have tumor lesions accessible for biopsy for
             correlative studies; in cases where there is a medical contraindication to tumor
             biopsy, exception may be granted upon discussion with the Principal Investigator/Chair

          -  The effects of CCI-779 on the developing human fetus at the recommended therapeutic
             dose are unknown; for this reason, women of childbearing potential and men must agree
             to use adequate contraception (hormonal or barrier method of birth control;
             abstinence) prior to study entry and for the duration of study participation; should a
             woman become pregnant or suspect she is pregnant while participating in this study,
             she should inform her treating physician immediately

          -  Ability to understand and the willingness to sign a written informed consent document

        Exclusion Criteria:

          -  Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
             nitrosoureas or mitomycin C) prior to entering the study or those who have not
             recovered from adverse events due to agents administered more than 4 weeks earlier

          -  Patients may not be receiving any other investigational agents concurrently or within
             4 weeks of study entry

          -  Patients with known brain metastases should be excluded from this clinical trial
             because of their poor prognosis and because they often develop progressive neurologic
             dysfunction that would confound the evaluation of neurologic and other adverse events

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to CCI-779

          -  Concurrent cancer from another primary site requiring treatment of any kind within the
             past 3 years; curatively treated non-melanoma skin cancer or in situ carcinoma of the
             cervix are allowed

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements

          -  Pregnant women are excluded from this study because CCI-779 is an inhibitor of mRNA
             translation with the potential for teratogenic or abortifacient effects; because there
             is an unknown but potential risk for adverse events in nursing infants secondary to
             treatment of the mother with CCI-779, breastfeeding should be discontinued if the
             mother is treated with CCI-779

          -  HIV-positive patients receiving combination anti-retroviral therapy are excluded from
             the study because of possible pharmacokinetic interactions with CCI-779; appropriate
             studies will be undertaken in patients receiving combination anti-retroviral therapy
             when indicated