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A Phase II Study of CCI-779 in Metastatic Neuroendocrine Carcinomas

Phase 2
18 Years
Not Enrolling
Metastatic Gastrointestinal Carcinoid Tumor, Pulmonary Carcinoid Tumor, Recurrent Gastrointestinal Carcinoid Tumor, Recurrent Islet Cell Carcinoma

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Trial Information

A Phase II Study of CCI-779 in Metastatic Neuroendocrine Carcinomas


I. To assess the objective tumor response rate (i.e. partial or complete responses as
defined by the RECIST criteria) in patients with progressive metastatic neuroendocrine
tumours given CCI-779.

II. To assess the stable disease rate and duration, time to progression, median survival
time, 1-year survival rate and toxicity in patients with metastatic neuroendocrine
carcinomas given CCI-779. As of 19 July 2010, overall survival follow-up is to be
discontinued for the four remaining patients on long term follow-up. At that point in time,
these patients had been off-treatment for 3 to 5 years. Time to progression and median
survival times will be based on the currently available data.

III. To measure baseline levels of various elements up- and downstream of the mammalian
target of rapamycin (mTOR). Where post-treatment biopsies are available, they will be
analyzed for suppression of elements in the mTOR pathway as well as for any effect on cell
cycle progression, apoptosis or anti-angiogenic effects.

OUTLINE: This is an open-label, multicenter study.

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 complete response (CR) or partial response (PR) receive 2
additional courses beyond CR or PR.

Patients are followed up for survival.

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

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Objective tumor response rate (defined as partial or complete response as defined by the RECIST criteria)

Outcome Description:

Potential association between variables will be measured using Pearson correlation coefficients, chi-square tests, one- or two-sample t-tests or logistic regression analyses as appropriate. Ninety-five percent confidence intervals will be constructed and selected results will be illustrated using figures and plots.

Outcome Time Frame:

Up to 8 years

Safety Issue:


Principal Investigator

Lillian Siu

Investigator Role:

Principal Investigator

Investigator Affiliation:

Princess Margaret Hospital Phase 2 Consortium


United States: Food and Drug Administration

Study ID:




Start Date:

December 2003

Completion Date:

Related Keywords:

  • Metastatic Gastrointestinal Carcinoid Tumor
  • Pulmonary Carcinoid Tumor
  • Recurrent Gastrointestinal Carcinoid Tumor
  • Recurrent Islet Cell Carcinoma
  • Carcinoid Tumor
  • Carcinoma
  • Carcinoma, Neuroendocrine
  • Malignant Carcinoid Syndrome
  • Gastrointestinal Neoplasms
  • Carcinoma, Islet Cell