Clinical trial NCT00017199: PS-341 in Treating Patients With Metastatic Neuroendocrine Tumors
Official title: Phase II Study of PS-341 in Metastatic Neuroendocrine Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Gastrointestinal Carcinoid Tumor
Islet Cell Tumor
Keywords: metastatic gastrointestinal carcinoid tumor
gastrinoma
insulinoma
somatostatinoma
glucagonoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-02-16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
city: Columbus
country: United States
facility: Arthur G. James Cancer Hospital - Ohio State University
state: Ohio
Study officials:
affiliation: Ohio State University Comprehensive Cancer Center
name: Manisha H. Shah, MD
role: STUDY_CHAIR
References: