A Phase II Trial of Bay 43-9006 in Progressive Metastatic Neuroendocrine Tumors

Inclusion Criteria

Criteria:

- Histologically confirmed neuroendocrine tumor:

- Carcinoid tumor OR islet cell carcinoma/other well-differentiated tumor

- No anaplastic or high-grade histology

- Metastatic disease

- Measurable disease

- No thyroid carcinoma of any histology, thymoma, or pheochromocytoma/paraganglioma

- No known brain metastases

- Performance status:

- ECOG 0-2

- Life expectancy:

- At least 24 weeks

- Hematopoietic:

- Absolute neutrophil count >= 1,500/mm3

- Platelet count >= 100,000/mm3

- No bleeding diathesis

- Hepatic:

- Bilirubin =< 2 times upper limit of normal (ULN)

- AST =< 3 times ULN (5 times ULN if liver metastases are present)

- INR normal

- PTT normal

- Renal:

- Creatinine =< 1.5 times ULN

- Cardiovascular:

No poorly controlled hypertension; No symptoms of congestive heart failure; No unstable
angina pectoris; No cardiac arrhythmia

- Gastrointestinal:

- Able to swallow capsules intact

- No gastrointestinal tract disease resulting in an inability to take oral
medication (e.g., dysphagia)

- No requirement for IV alimentation

- No active peptic ulcer disease

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No ongoing or active infection

- No psychiatric illness or social situation that would preclude study compliance

- No other invasive malignancy within the past 3 years except adequately treated basal
cell or squamous cell skin cancer or carcinoma in situ of the cervix

- No other uncontrolled illness

- At least 4 weeks since prior interferon

- No more than 1 prior systemic chemotherapy regimen:

Chemoembolization is not considered systemic chemotherapy

- At least 4 weeks since prior chemoembolization

- At least 3 weeks since prior radiotherapy

- No prior procedures adversely affecting intestinal absorption

- At least 4 weeks since prior hepatic artery embolization

- No other prior systemic therapy

- No other concurrent investigational treatment

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No concurrent enzyme-inducing anticonvulsants (e.g., carbamazepine, phenobarbital, or
phenytoin)

- No concurrent rifampin

- No concurrent Hypericum perforatum (St. John's wort)

- Prior or concurrent octreotide for symptomatic treatment allowed

- No concurrent therapeutic anticoagulation:

Concurrent prophylactic anticoagulation (i.e., low dose warfarin) of venous or arterial
access devices allowed provided requirements for INR or PTT are met

- At least 4 weeks since prior major surgery

- Recovered from all prior therapy