Overview

Temsirolimus in Treating Patients With Metastatic Neuroendocrine Carcinoma

Status:
Completed
Trial end date:
2011-04-01
Target enrollment:
0
Participant gender:
All
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.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
National Cancer Institute (NCI)
Treatments:
Everolimus
Sirolimus
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