RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase II trial to study the effectiveness of PS-341 in treating patients who have metastatic neuroendocrine tumors.

Condition	Treatment or Intervention	Phase
miscellaneous islet cell cancer Gastrinoma Insulinoma Somatostatinoma Glucagonoma metastatic gastrointestinal carcinoid tumor	Procedure: enzyme inhibitor therapy  Drug: PS-341	Phase II

Further Study Details: 

OBJECTIVES: I. Determine the objective response rate of patients with metastatic neuroendocrine tumors treated with PS-341. II. Determine the toxicity of this drug in this patient population. III. Determine the pharmacodynamics to correlate proteasome inhibition and efficacy of this drug in this patient population.

PROTOCOL OUTLINE: This is a multicenter study. Patients receive PS-341 IV over 3-5 seconds on days 1, 4, 8, and 11. Treatment repeats every 21 days for at least 8 courses in the absence of disease progression or unacceptable toxicity. Patients achieving complete response (CR) receive 2 additional courses beyond CR.

PROJECTED ACCRUAL: A total of 16-25 patients will be accrued for this study within 6 months.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed metastatic carcinoid tumor or islet cell tumor; Well-differentiated neuroendocrine tumor OR Well-differentiated neuroendocrine carcinoma
• Measurable disease in at least 1 dimension; At least 20 mm by conventional techniques OR At least 10 mm by spiral CT scan The following are considered nonmeasurable: Lesions in a previously irradiated area; Bone lesions; Leptomeningeal disease; Ascites; Pleural/pericardial effusion; Lymphangitis cutis/pulmonis; Abdominal masses that are not confirmed and followed Cystic lesions

--Prior/Concurrent Therapy--

• Biologic therapy: At least 4 weeks since prior immunotherapy (interferon alfa)
• Chemotherapy: No more than 1 prior systemic chemotherapy regimen (except hepatic artery chemoembolization); At least 4 weeks since prior systemic chemotherapy (6 weeks for nitrosoureas); At least 12 weeks since prior hepatic artery chemoembolization (unless liver lesions are not indicator lesions); Stable dose long-acting octreotide therapy (Sandostatin LAR) within the past 3 months allowed; Concurrent subcutaneous octreotide for breakthrough symptomatic relief allowed
• Endocrine therapy: Not specified
• Radiotherapy: See Disease Characteristics; At least 4 weeks since prior radiotherapy
• Surgery: Not specified
• Other: No other concurrent investigational agents, commercial agents, or therapies; No concurrent combination antiretroviral therapy for HIV-positive patients

--Patient Characteristics--

• Age: 18 and over
• Performance status: ECOG 0-2
• Life expectancy: At least 6 months
• Hematopoietic: Leukocyte count at least 3,000/mm3; Absolute neutrophil count at least 1,500/mm3; Platelet count at least 100,000/mm3
• Hepatic: Bilirubin no greater than 1.5 mg/dL; AST/ALT no greater than 2.5 times upper limit of normal
• Renal: Creatinine no greater than 1.5 mg/dL
• Cardiovascular: No symptomatic congestive heart failure; No unstable angina pectoris; No cardiac arrhythmia
• Other: No other uncontrolled illness; No ongoing active infection; No psychiatric illness or social situation that would preclude study; No history of allergic reaction to compounds of similar chemical or biologic composition to PS-341; Not pregnant or nursing; Negative pregnancy test; Fertile patients must use effective contraception

Illinois
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637-1470,  United States
Ohio
      Arthur G. James Cancer Hospital - Ohio State University, Columbus,  Ohio,  43210-1240,  United States

Study chairs or principal investigators

Manisha H. Shah,  Study Chair,  Arthur G. James Cancer Hospital & Richard J. Solove Research Institute   

Study ID Numbers:  CDR0000068660; OSU-00H0328; NCI-1856
Record last reviewed:  February 2004
Last Updated:  October 13, 2004
Record first received:  June 6, 2001
ClinicalTrials.gov Identifier:  NCT00017199
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08