Study Chairman:  Jaffer A. Ajani, MD
Study Sponsor:  Upjohn/Pharmacia

Study Drug administration:  CPT-11 administerd at 125 mg/M2 over 90 minutes 
weekly for four weeks followed by a two-week rest period.  (one course).  
Courses will be repeated 
every six weeks.

STUDY RATIONALE

From the protocol abstract.

CPT-11 is a topoisomerase-1 inhibitor with evidnce of activity against colorectal carcinoma. This drug has activity in a number of other tumor types. It has not been studied in patients with carcinoid tumors or islet cell carcinoma. Similar to colon carcinoma, carcinoid tumors are generally resistant to chemotherapy and are also known to have p-glycoprotein on the cell surface. Islet cell carcinoma is more sensitive to chemotherapy than carcinoid tumors, however, the options are quite limited in this group of patients as well. No new agent has been identified for this group of patients in the last 15 years. It would be worthwhile exploring the activity of CPT-11 against these tumors.

Inclusion:

Must have histologic documented metastatic, unresectable neuroendocrine tumors: carcinoid or islet cell tumors. Patients with metastatic neuroendocrine tumors and no obvious primary without carcinoid syndrome may be considered to have an islet cell carcinoma.

For Carcinoid Tumors:

No prior chemotherapy allowed. Prior or concurrent somatostatin analogue therapy for the control of carcinoid syndrome will be allowed. Prior hepatic artery embolization will be allowed provided patients still have clearly measurable disease.

For Islet Cell Tumors:

Patients must hve received one prior regimen, preferably containing streptozoicin and doxorubicin.

For All Patients on Study:

Must have bidimensionally measurable disease on CT or MRI at least 2 cm in diameter.

Patients must be at least 10 years old.

Must have adequate liver and kidney function and blood counts.

Exclusion:

Patients who have previously received CPT-11 or Topotecan.

Patients with any active or uncontrolled infection including HIV.

Pregant or lactating women. Effective contraception is required.

Presence of clinically apparent central nervous system metastases or carcinomatous meningitis.

Patients with a history of seizures are ineligible. Patients receiving Phenytoin, Phenobarbital, or other antiepileptic medication are ineligible.

Patients with uncontrolled diabetes.

Patients with a baseline serum calcium >12.0 mg/dL

Patients with known Gilbert's Syndrome, as these patients may have excessive CPT-11-induced toxicity.

Patients with psychiatric disorders that would interfere with giving informed consent or following up.

Patients with a history of myocardial infarction (heart attack) within the previous six months or congestive heart failure requiring therapy.

Patients with a history of prior other cancer, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which they have been disease-free for at least 5 years.

Patients with significant diarrhea not controlled with medications. (including octreotide in patients with carcinoid syndrome.)