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Arsenic Trioxide and Pamidronate in Treating Patients With Advanced Solid Tumors or Multiple Myeloma

Primary Purpose

Refractory Multiple Myeloma, Unspecified Adult Solid Tumor, Protocol Specific

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
pamidronate disodium
arsenic trioxide
laboratory biomarker analysis
pharmacological study
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Refractory Multiple Myeloma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 interval 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 radiotherapy 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

Sites / Locations

  • City of Hope

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (pamidronate disodium and arsenic trioxide)

Arm Description

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.

Outcomes

Primary Outcome Measures

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
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.

Secondary Outcome Measures

Survival
Time to failure

Full Information

First Posted
July 26, 2005
Last Updated
January 4, 2013
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00124605
Brief Title
Arsenic Trioxide and Pamidronate in Treating Patients With Advanced Solid Tumors or Multiple Myeloma
Official Title
Phase I Trial of Arsenic Trioxide in Combination With Pamidronate Disodium
Study Type
Interventional

2. Study Status

Record Verification Date
January 2013
Overall Recruitment Status
Completed
Study Start Date
April 2005 (undefined)
Primary Completion Date
June 2009 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
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 them from dividing. Arsenic trioxide and pamidronate 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. 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
Detailed Description
PRIMARY OBJECTIVES: 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Refractory Multiple Myeloma, Unspecified Adult Solid Tumor, Protocol Specific

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (pamidronate disodium and arsenic trioxide)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
pamidronate disodium
Other Intervention Name(s)
Aminomux, APD, Aredia, GCP-23339A
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
arsenic trioxide
Other Intervention Name(s)
Arsenic (III) Oxide, Arsenic Sesquioxide, Arsenous Acid Anhydride, AS2O3, Trisenox
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Intervention Type
Other
Intervention Name(s)
pharmacological study
Other Intervention Name(s)
pharmacological studies
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
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
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.
Time Frame
28 days
Secondary Outcome Measure Information:
Title
Survival
Time Frame
Up to 4 years
Title
Time to failure
Time Frame
Up to 4 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 interval 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 radiotherapy 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Przemyslaw Twardowski
Organizational Affiliation
City of Hope Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States

12. IPD Sharing Statement

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Arsenic Trioxide and Pamidronate in Treating Patients With Advanced Solid Tumors or Multiple Myeloma

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