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Phase I Trial of Arsenic Trioxide in Combination With Pamidronate Disodium

Phase 1
18 Years
Not Enrolling
Refractory Multiple Myeloma, Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

Phase I Trial of Arsenic Trioxide in Combination With Pamidronate Disodium


I. To describe the toxicities of the combination of arsenic trioxide in combination with
pamidronate disodium at four dose levels.

II. To assess the pharmacokinetics of pamidronate disodium when given in combination with
arsenic trioxide.

III. Utilizing 2-color immunofluorescence (IF) to determine if the treatment with
combination of arsenic trioxide and pamidronate disodium affects the phosphorylation of
epidermal growth factor receptor (EGFR) IV. In patients with multiple myeloma utilizing
western blot to evaluate the pre- and post-treatment levels of protein tyrosine phosphatase
1B in lysates of multiple myeloma cells.

V. To obtain preliminary data for response to this regimen in this patient population.

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.

Inclusion Criteria:

- Patients with histologically or cytologically proven diagnosis of solid tumors or
multiple myeloma refractory to standard therapy or for which no satisfactory
treatment exists at the time of enrollment

- Patient must be capable of understanding the nature of the trial and must give
written informed consent

- Patients must have a WHO performance status of 0, 1, or 2

- Patients must have life expectancy of at least three months

- Absolute neutrophil count of > 1x10^9 /L

- Platelet count > 75 x 10^9 /L

- Calculated creatinine clearance of > 50 mL/min

- Serum bilirubin =< 1.5 x the institutional upper limit of normal

- SGOT (AST) and SGPT (ALT) must be =< 2.5 x the institutional upper limit of normal

- All patients must be willing to use adequate contraception

- Patients with brain metastases which at the time of study enrollment are controlled
and do not require treatment with corticosteroids are eligible

- Patients must not have a prolonged QT interval > 460 milliseconds on baseline ECG in
the presence of normal serum potassium and magnesium values; ECG must be obtained
within 28 days prior to registration

- Patients must not be receiving or planning to receive drugs known to prolong the QT

- Patients previously or currently treated with pamidronate or other bisphosphonates
are eligible after a wash-out period of 28 days; concurrent treatment with other
bisphosphonates is not allowed

- Patients must not have a history of torsades de pointes type ventricular arrhythmia

Exclusion Criteria:

- Patients who have had radiotherapy or chemotherapy within three weeks (nitrosoureas
or mitomycin C within six weeks) prior to anticipated first day of dosing; patients
must be fully recovered from the acute effects of any prior chemotherapy or

- Patients with uncontrolled electrolyte imbalance (NA < 132 mmol/L; K < 3.5 mmol/L; Mg
< 1.7 mg/dL)

- Patients undergoing therapy with other investigational agents; patients must have
recovered from all acute effects of previously administered investigational agents
and sufficient time must have elapsed since last administration to ensure the drug
interactions not occur during this study

- Patients who are pregnant or breast-feeding will be excluded

- Patients with history of hypersensitivity to pamidronate or other bisphosphonates

- Patients previously treated with arsenic trioxide are not eligible

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

MTD defined as the highest dose tested in which greater than 33% of patients experienced dose limiting toxicity (DLT) assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0

Outcome Description:

The toxicities observed at each dose level will be summarized in terms of type, severity, time of onset, duration, and reversibility or outcome. Tables will be created to summarize these toxicities and side effects by dose and by course. Tabular and graphical summaries will be used to explore the relationship of type and grade of toxicity to dose, course, and pharmacokinetics.

Outcome Time Frame:

28 days

Safety Issue:


Principal Investigator

Przemyslaw Twardowski

Investigator Role:

Principal Investigator

Investigator Affiliation:

Beckman Research Institute


United States: Food and Drug Administration

Study ID:




Start Date:

April 2005

Completion Date:

Related Keywords:

  • Refractory Multiple Myeloma
  • Unspecified Adult Solid Tumor, Protocol Specific
  • Multiple Myeloma
  • Neoplasms, Plasma Cell



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