Intervention: Temsirolimus
Trial phase: Phase 2
ATC code: L01EG01 | L01XE09
SMILES: COC1CC2CCC(C)C(O)(O2)C(=O)C(=O)N2CCCCC2C(=O)OC(C(C)CC2CCC(OC(=O)C(C)(CO)CO)C(OC)C2)CC(=O)C(C)C=C(C)C(O)C(OC)C(=O)C(C)CC(C)C=CC=CC=C1C
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 36
Group description: Patients receive CCI-779 IV over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve a CR or PR receive 2 additional courses beyond CR or PR.

temsirolimus: Given IV

laboratory biomarker analysis: Correlative studies
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