RATIONALE: Drugs used in chemotherapy, such as arsenic trioxide and pamidronate, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping the cells from dividing. They may also stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Pamidronate may also stop the growth of cancer cells by blocking blood flow to the cancer. Giving arsenic trioxide together with pamidronate may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of arsenic trioxide and pamidronate in treating patients with advanced solid tumors or multiple myeloma.

Condition	Intervention	Phase
unspecified adult solid tumor, protocol specific refractory plasma cell neoplasm stage III multiple myeloma stage II multiple myeloma	Drug: arsenic trioxide  Drug: pamidronate  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: enzyme inhibitor therapy  Procedure: growth factor antagonist therapy  Procedure: protein tyrosine kinase inhibitor therapy	Phase I

Further Study Details: 

OBJECTIVES:

• Determine the maximum tolerated dose of arsenic trioxide and pamidronate in patients with advanced solid tumors or multiple myeloma.
• Determine the toxic effects of this regimen in these patients.
• Determine the pharmacokinetics of this regimen in these patients.
• Determine, preliminarily, response in patients treated with this regimen.

OUTLINE: This is a dose-escalation, multicenter study.

Patients receive pamidronate IV and over 2 hours on days 1 and 15 and arsenic trioxide IV over 2 hours on days 1-5 and 15-19. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of pamidronate and arsenic trioxide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicity.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: Approximately 12-24 patients will be accrued for this study.

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

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed solid tumors or multiple myeloma
• Advanced disease
• Refractory to standard therapy OR no standard therapy exists
• Brain metastases allowed provided they are controlled and patient does not require treatment with corticosteroids

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• WHO 0-2

Life expectancy

• At least 3 months

Hematopoietic

• Absolute neutrophil count > 1,000/mm^3
• Platelet count > 75,000/mm^3

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 2.5 times ULN

Renal

• Creatinine clearance > 50 mL/min

Cardiovascular

• QT interval ≤ 460 msec by ECG AND potassium normal AND magnesium normal
• No history of torsades de pointes-type ventricular arrhythmia

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No history of hypersensitivity to pamidronate or other bisphosphonates
• No uncontrolled electrolyte imbalance, including any of the following:
• Sodium < 132 mmol/L
• Potassium < 3.5 mmol/L
• Magnesium < 1.7 mg/dL

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
• No prior arsenic trioxide

Endocrine therapy

• See Disease Characteristics

Radiotherapy

• More than 3 weeks since prior radiotherapy and recovered

Surgery

• Not specified

Other

• Recovered from prior investigational agents.
• At least 28 days since prior pamidronate or other bisphosphonates.
• No other concurrent bisphosphonates
• No other concurrent antineoplastic therapy
• No concurrent drugs known to prolong the QT interval
• No other concurrent investigational agents

Please refer to this study by ClinicalTrials.gov identifier  NCT00124605

California
      City of Hope Comprehensive Cancer Center, Duarte,  California,  91010-3000,  United States; Recruiting
Illinois
      Cardinal Bernardin Cancer Center at Loyola University Medical Center, Maywood,  Illinois,  60153,  United States; Recruiting
      Central Illinois Hematology Oncology Center, Springfield,  Illinois,  62701,  United States; Recruiting
      Decatur Memorial Hospital Cancer Care Institute, Decatur,  Illinois,  62526,  United States; Recruiting
      Evanston Northwestern Health Care - Evanston Hospital, Evanston,  Illinois,  60201-1781,  United States; Recruiting
      Ingalls Cancer Care Center at Ingalls Memorial Hospital, Harvey,  Illinois,  60426,  United States; Recruiting
      La Grange Memorial Hospital, La Grange,  Illinois,  60525,  United States; Recruiting
      Louis A. Weiss Memorial Hospital, Chicago,  Illinois,  60640,  United States; Recruiting
      Oncology/Hematology Associates of Central Illinois, P.C., Peoria,  Illinois,  61615-7828,  United States; Recruiting
Indiana
      CCOP - Northern Indiana CR Consortium, South Bend,  Indiana,  46601,  United States; Recruiting
      Fort Wayne Medical Oncology and Hematology, Incorporated, Fort Wayne,  Indiana,  46885-5099,  United States; Recruiting
Michigan
      Lakeland Cancer Care Center at Lakeland Hospital - St. Joseph, Saint Joseph,  Michigan,  49085,  United States; Recruiting

Study chairs or principal investigators

Przemyslaw W. Twardowski, MD,  Study Chair,  Beckman Research Institute   

Study ID Numbers:  CDR0000434807; CCC-PHI-45; NCI-6458
Last Updated:  August 1, 2005
Record first received:  July 27, 2005
ClinicalTrials.gov Identifier:  NCT00124605
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-08-02