Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Bortezomib in Treating Patients With Advanced or Metastatic Sarcoma

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Closed	18 and over	NCI	MSKCC-01073 NCI-1757, NCT00027716, 1757

Objectives

1. Determine the response rate in patients with advanced or metastatic sarcoma treated with bortezomib.
2. Correlate levels of cyclins D1, E, p21 (WAF1), p27 (Kip1), mdm², p53, and Ki67 with response in patients treated with this drug.

Entry Criteria

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

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

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/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

  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

Expected Enrollment

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.)

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.

Trial Contact Information

Trial Lead Organizations

Memorial Sloan-Kettering Cancer Center

Robert Maki, MD, PhD, Protocol chair		Ph: 212-639-5720; 800-525-2225

Registry Information
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
Trial Start Date		2001-10-02
Registered in ClinicalTrials.gov		NCT00027716
Date Submitted to PDQ		2001-10-12
Information Last Verified		2004-08-11
NCI Grant/Contract Number		N01-CM17105, P30-CA08748, U01-CA69913

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