PS-341 in Treating Patients With Metastatic Neuroendocrine Tumors

Phase II Study of PS-341 in Metastatic Neuroendocrine Tumors

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.

Study Overview

• Status: Completed
• Conditions: Islet Cell Tumor; Gastrointestinal Carcinoid Tumor
• Intervention / Treatment: Drug: bortezomib

Detailed 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.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: Ohio State University Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Manisha H. Shah, MD, Ohio State University Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start: April 1, 2001
• Study Completion (Actual): May 1, 2007

Study Registration Dates

• First Submitted: June 6, 2001
• First Submitted That Met QC Criteria: February 13, 2004
• First Posted (Estimate): February 16, 2004

Study Record Updates

• Last Update Posted (Estimate): January 31, 2013
• Last Update Submitted That Met QC Criteria: January 30, 2013
• Last Verified: May 1, 2007

More Information

Terms related to this study

• Keywords: metastatic gastrointestinal carcinoid tumor; gastrinoma; insulinoma; glucagonoma; somatostatinoma
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Digestive System Neoplasms; Gastrointestinal Diseases; Endocrine Gland Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Pancreatic Diseases; Adenoma; Pancreatic Neoplasms; Neoplasms; Gastrointestinal Neoplasms; Neuroendocrine Tumors; Carcinoid Tumor; Adenoma, Islet Cell; Malignant Carcinoid Syndrome; Antineoplastic Agents; Bortezomib
• Other Study ID Numbers: CDR0000068660; OSU-00H0328; NCI-1856