Bortezomib in Treating Patients With Advanced or Metastatic Sarcoma

Sarcoma Clinical Trial

Official title:

A Multi-Institutional, Open-Label, Two-Group, Phase II Study of PS-341 (LDP-341, NSC #681239) in Patients With Advanced or Metastatic Sarcoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00027716
• Other study ID #: 01-073
• Secondary ID: CDR0000069060NCI
• Status: Completed
• Phase: Phase 2
• First received: December 7, 2001
• Last updated: June 4, 2013
• Start date: October 2001
• Est. completion date: May 2004

Study information

• Verified date: June 2013
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Bortezomib may stop the growth of cancer by blocking the enzymes necessary for tumor cell growth.

PURPOSE: Phase II trial to study the effectiveness of bortezomib in treating patients who have advanced or metastatic sarcoma.

Description:

OBJECTIVES:

• Determine the response rate in patients with advanced or metastatic sarcoma treated with bortezomib.

• Correlate levels of cyclins D1, E, p21 (WAF1), p27 (Kip1), mdm^2, p53, and Ki67 with response in patients treated with this drug.

OUTLINE: This is an open-label, multicenter study. Patients are stratified according to disease (stratum I: soft tissue sarcoma not specified in stratum II, osteogenic sarcoma arising from soft tissues, or gastrointestinal stromal tumor vs stratum II: Ewing's sarcoma of soft tissue or bone, rhabdomyosarcoma, or osteogenic sarcoma of bone). (Stratum I closed to accrual as of 10/17/03.)

Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 1 year.

PROJECTED ACCRUAL: A total of 21-41 patients will be accrued for stratum I within 5-11 months and 21-41 patients will be accrued for stratum II within 10.5-22 months. (Stratum I closed to accrual as of 10/17/03.)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. completion date: May 2004
• Est. primary completion date: May 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed sarcoma

• Soft tissue metastasis or locally recurrent disease

• Stratum I (closed to accrual as of 10/17/03):

• Soft tissue sarcoma not specified in stratum II

• Osteogenic sarcoma arising from soft tissue or gastrointestinal stromal tumor (GIST)

• Stratum II:

• Ewing's sarcoma of soft tissue or bone (if measurable soft tissue metastasis is present)

• Rhabdomyosarcoma

• Osteogenic sarcoma of bone (if measurable soft tissue metastasis is present)

• At least 1 unidimensionally measurable lesion

• At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan

• Disease progression within the past 3 months

• No prior or active known brain metastases

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 80-100% OR

• ECOG 0-1

Life expectancy:

• Not specified

Hematopoietic:

• 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 OR

• Creatinine clearance greater than 60 mL/min

Cardiovascular:

• No peripheral vascular disease requiring surgical management

• No history of congestive heart failure even if it is medically controlled

• No angina pectoris even if it is medically controlled

• No myocardial infarction within the past year

• No cardiac arrhythmias

• No prior cerebrovascular event

• No prior transient ischemic attack

• No EKG evidence of acute ischemia or conduction abnormality (e.g., bifascicular block [left anterior hemiblock in the presence of right bundle branch block] or second or third degree atrioventricular block)

• No history of orthostatic hypotension

Other:

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No prior allergic reaction to compounds of similar chemical or biological composition to study drug

• No other uncontrolled concurrent illness

• No ongoing or active infection

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

• No other malignancy within the past 5 years except adequately treated basal cell skin cancer or carcinoma in situ of the cervix

• No symptomatic peripheral neuropathy greater than grade 1

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 4 weeks since prior immunotherapy and recovered

• No concurrent biological or immunological agents

Chemotherapy:

• Stratum I (closed to accrual as of 10/17/03):

• At least 1 year since prior chemotherapy in the adjuvant or neoadjuvant setting

• No other prior chemotherapy

• Stratum II:

• No more than 1 prior chemotherapy regimen

• No concurrent chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 4 weeks since prior radiotherapy and recovered

• No concurrent radiotherapy

Surgery:

• Not specified

Other:

• Prior imatinib mesylate for GIST (stratum I closed to accrual as of 10/17/03) allowed

• No other concurrent investigational agents

• No concurrent commercial anticancer agents or therapies

• No concurrent combination antiretroviral therapy for HIV-positive patients

Study Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Sarcoma

Intervention

Drug:
• bortezomib

Locations

Country	Name	City	State
United States	University of Colorado Cancer Center at University of Colorado Health Sciences Center	Aurora	Colorado
United States	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts
United States	Albert Einstein College of Medicine	Bronx	New York
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	University of Chicago Cancer Research Center	New York	New York
United States	Abramson Cancer Center at University of Pennsylvania Medical Center	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States,