PS-341 in Treating Patients With Metastatic Neuroendocrine Tumors

The Ohio State University

Status and phase: Completed; Phase 2

Conditions: Islet Cell Tumor; Gastrointestinal Carcinoid Tumor

Treatments: Drug: bortezomib

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00017199

OSU-00H0328

CDR0000068660

NCI-1856

Details and patient eligibility

About

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.

Full description

OBJECTIVES:

• Determine the objective response rate of patients with metastatic neuroendocrine tumors treated with bortezomib.
• Determine the toxicity of this drug in this patient population.
• Determine the pharmacodynamics to correlate proteasome inhibition and efficacy of this drug in this patient population.

OUTLINE: This is a multicenter study.

Patients receive bortezomib 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.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• At least 6 months

Hematopoietic:

• Leukocyte count at least 3,000/mm^3
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

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 bortezomib
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

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