RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Omeprazole may increase the effectiveness of bortezomib. Giving omeprazole together with bortezomib may kill more cancer cells.

PURPOSE: This randomized phase I trial is studying the side effects and best way to give omeprazole and bortezomib in treating patients with advanced solid tumors or non-Hodgkin’s lymphoma.

Condition	Treatment or Intervention	Phase
adult lymphomatoid granulomatosis adult non-Hodgkin's lymphoma adult solid tumor indolent or aggressive adult non-Hodgkin's lymphoma	Drug: bortezomib  Drug: omeprazole  Procedure: drug modulation  Procedure: enzyme inhibitor therapy  Procedure: proton pump inhibitor therapy	Phase I

Further Study Details: 

OBJECTIVES: Primary

• Determine the effect of omeprazole on the pharmacokinetics and safety profile of bortezomib in patients with advanced solid tumors or non-Hodgkin’s lymphoma.

Secondary

• Determine the effect of omeprazole on the pharmacodynamics of bortezomib in these patients.

OUTLINE: This is an open-label, randomized, crossover, multicenter study. Patients are stratified according to participating center. Patients are randomized to 1 of 2 treatment arms.

• : Patients receive 2 courses of treatment (21 days apart), in the absence of disease progression or unacceptable toxicity, as follows:
• Course 1: Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Patients also receive oral omeprazole once daily on days 6, 7, 9, and 10 and twice daily on day 8.
• Course 2: Patients receive bortezomib alone IV over 3-5 seconds on days 1, 4, 8, and 11.
• : Patients receive 2 courses of treatment (21 days apart), in the absence of disease progression or unacceptable toxicity, as follows:
• Course 1: Patients receive bortezomib alone as in arm I, course 2.
• Course 2: Patients receive bortezomib and omeprazole as in arm I, course 1. After completion of course 2, all patients are assessed for response. Patients who benefit from treatment may receive 6 additional courses of bortezomib alone as above.

After completion of study treatment, patients are followed at approximately 30 days.

PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of 1 of the following:
• Solid tumors
• No tumors for which single-agent therapy with bortezomib has been ineffective, including the following:
• Breast cancer
• Pancreatic cancer
• Other biliary tract cancer
• Non-Hodgkin's lymphoma
• Advanced disease
• No currently available therapy or protocol of higher priority exists

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• Karnofsky 70-100%

Life expectancy

• At least 3 months

Hematopoietic

• Hemoglobin ≥ 10 g/dL
• Absolute neutrophil count ≥ 1,000/mm^3
• Platelet count ≥ 100,000/mm^3
• No red blood cell or platelet transfusion dependence*
• Patients who received 1 transfusion are eligible provided they are not transfusion dependent* NOTE: *Transfusion dependence is defined as treatment with an average of 4-6 red blood cell and/or platelet transfusions within the past 6 months (i.e., ≥ 1 transfusion/month)

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 2 times ULN
• Hepatitis B surface antigen negative
• Hepatitis C antibody negative
• No history of clinically relevant liver insufficiency

Renal

• Creatinine clearance ≥ 50 mL/min
• Calcium normal
• No history of clinically relevant renal insufficiency

Cardiovascular

• No myocardial infarction within the past 6 months
• No New York Heart Association class III or IV congestive heart failure
• No uncontrolled angina
• No clinically significant pericardial disease
• No cardiac amyloidosis
• No other uncontrolled or severe cardiovascular disease
• No history of hypotension, defined as sitting systolic blood pressure ≤ 100 mmHg and/or sitting diastolic blood pressure ≤ 60 mmHg
• No other significant cardiovascular disturbance

Pulmonary

• No significant pulmonary disturbance

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Weight ≥ 50 kg
• Body mass index ≤ 28 kg/m^2
• Able to swallow capsules intact (without chewing, crushing, or opening)
• No known or suspected hypersensitivity or intolerance to omeprazole, boron, mannitol, or heparin, if an indwelling catheter is used
• No alcohol or drug abuse within the past 12 months
• Negative drug and alcohol screen
• No uncontrolled diabetes
• If receiving antidiabetic agents, must be on a stable dose for ≥ 3 months before study entry
• No significant gastrointestinal, endocrine, neurologic, rheumatologic, psychiatric, or metabolic disturbance
• No active systemic infection requiring treatment
• No neuropathy ≥ grade 1
• No jogging, strenuous exercise, or sunbathing for 24 hours after the day 8 bortezomib dose (during courses 1 and 2 of study treatment)
• HIV negative
• Not an employee of the investigator or study center, with direct involvement in the proposed study or other studies under the direction of that investigator or study center
• Not a family member of the employee or the investigator

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• More than 4 weeks since prior systemic chemotherapy

Endocrine therapy

• More than 2 weeks since prior glucocorticoids
• No concurrent corticosteroids (e.g., prednisone ≥ 10 mg/day or its equivalent) or glucocorticoids*
• Concurrent megestrol allowed NOTE: *During courses 1 and 2 of study treatment; may be allowed during courses 3-8 of study treatment at the discretion of the investigator

Radiotherapy

• More than 4 weeks since prior extensive radiotherapy

Surgery

• No preplanned surgery or procedure that would preclude study participation

Other

• Recovered from prior antineoplastic therapy
• No prior bortezomib
• More than 6 months since prior and no concurrent nicotine-containing products, including the following tobacco products:
• Cigarettes
• Cigars
• Chewing tobacco
• Gum
• Patch
• More than 1 month since prior omeprazole
• More than 4 weeks since prior experimental drugs or medical devices
• More than 4 weeks since other prior antineoplastic therapy
• More than 2 weeks since prior and no concurrent* CYP2C19 or CYP3A4 inhibitors or inducers, including any of the following:
• Cimetidine
• Erythromycin
• Fluoxetine
• Ketoconazole
• Paroxetine
• Carbamazepine
• Phenobarbital
• Rifampin
• No ingestion of products containing alcohol, quinine, grapefruit juice, or Seville oranges for 1 week before the first dose of bortezomib and during courses 1 and 2 of study treatment
• No ingestion of methylxanthine-containing products, including caffeine (e.g., chocolate bars or beverages, coffee, tea, or colas) on day 8 of courses 1 and 2 of study treatment
• No other concurrent antineoplastic agents*
• No other concurrent experimental agents*
• No other concurrent proton pump inhibitors*
• Concurrent participation in a non-treatment study allowed provided the study would not interfere with participation in this study
• Concurrent cyclooxygenase-2 inhibitors or bisphosphonates allowed NOTE: *During courses 1 and 2 of study treatment; may be allowed during courses 3-8 of study treatment at the discretion of the investigator

California
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-1781,  United States; Recruiting

Study chairs or principal investigators

Carolyn Britten, MD,  Study Chair,  Jonsson Comprehensive Cancer Center   

Study ID Numbers:  CDR0000420923; UCLA-0409028-01; JJPRD-26866138-CAN-1001; JJPRD-JNJ-26866138
Record last reviewed:  March 2005
Last Updated:  April 5, 2005
Record first received:  April 5, 2005
ClinicalTrials.gov Identifier:  NCT00107302
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08