Bortezomib, Fluorouracil, and Leucovorin in Treating Patients With Metastatic or Unresectable Stomach Cancer

Sponsor

California Cancer Consortium (Other)

Overall Status

Terminated

CT.gov ID

NCT00103103

Collaborator

National Cancer Institute (NCI) (NIH)

Locations

Duration (Months)

Study Details

Study Description

Brief Summary

RATIONALE: Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as fluorouracil and leucovorin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bortezomib together with fluorouracil and leucovorin may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving bortezomib together with fluorouracil and leucovorin works in treating patients with metastatic or unresectable stomach cancer.

Condition or Disease	Intervention/Treatment	Phase
Gastric Cancer	Drug: bortezomib Drug: fluorouracil Drug: leucovorin calcium	Phase 2

Detailed Description

OBJECTIVES:

Primary

Determine response in patients with previously treated metastatic or unresectable gastric or gastroesophageal junction adenocarcinoma treated with bortezomib, fluorouracil, and leucovorin calcium.

Secondary

Determine time to progression and overall survival of patients treated with this regimen.
Determine the toxic effects of this regimen in these patients.

OUTLINE: This is a non-randomized, multicenter study.

Patients receive bortezomib IV over 3-5 seconds on days 1, 8, and 15. One hour after completion of bortezomib, patients receive leucovorin calcium IV and fluorouracil IV followed by fluorouracil IV continuously over 46 hours on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed for survival.

PROJECTED ACCRUAL: A total of 12-37 patients will be accrued for this study.

Study Design

Study Type:

Interventional

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II Combination Trial of PS-341 and 5-FU/LV in Gastric and/or GE Junction Adenocarcinoma

Study Start Date :

Mar 1, 2005

Actual Primary Completion Date :

Aug 1, 2005

Actual Study Completion Date :

Aug 1, 2005

Outcome Measures

Primary Outcome Measures

Response rate as measured by RECIST every 8 weeks []

Secondary Outcome Measures

Time to progression every 8 weeks []
Overall survival []
Toxicity every 4 weeks []
Molecular correlates on and off study treatment []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Diagnosis of gastric or gastroesophageal junction adenocarcinoma
Metastatic or unresectable disease
Progressive disease after receiving 1 prior chemotherapy regimen for metastatic disease comprising 1 of the following:
Fluorouracil
Cisplatin and irinotecan
Capecitabine
Taxanes
Measurable disease
No esophageal cancer
No brain metastases

PATIENT CHARACTERISTICS:

Age

Over 18

Performance status

ECOG 0-2 OR
Karnofsky 60-100%

Life expectancy

At least 3 months

Hematopoietic

Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3

Hepatic

Bilirubin normal
AST and ALT ≤ 2.5 times upper limit of normal

Renal

Creatinine ≤ 1.5 mg/dL

Cardiovascular

No symptomatic congestive heart failure
No unstable angina pectoris
No cardiac arrhythmia
No acute ischemia by EKG
No significant conduction abnormality by EKG, including either of the following:
Bifasicular block, defined as left anterior hemiblock in the presence of right bundle branch block
Second or third degree atrioventricular block
No history of cardiac or cerebrovascular disease due to hypotension and tachycardia

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception before, during, and for 6 months after study participation
No ongoing or active infection
No other uncontrolled illness
No peripheral neuropathy ≥ grade 2 within the past 2 weeks
No allergy to boron or mannitol

PRIOR CONCURRENT THERAPY:

Biologic therapy

More than 4 weeks since prior immunotherapy

Chemotherapy

More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas) and recovered

Endocrine therapy

Not specified

Radiotherapy

More than 4 weeks since prior radiotherapy and recovered

Surgery

More than 2 weeks since prior major surgery

Other

No concurrent highly active anti-retroviral therapy for HIV-positive patients
No other concurrent investigational agents

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010-3000
2	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California	United States	90089-9181
3	City of Hope Medical Group	Pasadena	California	United States	91105
4	University of California Davis Cancer Center	Sacramento	California	United States	95817
5	Hillman Cancer Center at University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania	United States	15232