Refractory Multiple MyelomaPhase 1NCT00124605
Arsenic Trioxide and Pamidronate in Treating Patients With Advanced Solid Tumors or Multiple Myeloma
A Phase 1 study testing pamidronate disodium, arsenic trioxide and laboratory biomarker analysis in people with Refractory Multiple Myeloma and Unspecified Adult Solid Tumor, Protocol Specific, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Refractory Multiple Myeloma, Unspecified Adult Solid Tumor, Protocol Specific
- What is being tested?
- pamidronate disodium, arsenic trioxide and laboratory biomarker analysis
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2005to Jun 2009
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 15Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase I Trial of Arsenic Trioxide in Combination With Pamidronate Disodium
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
Read the detailed description
PRIMARY OBJECTIVES:
- 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.
- 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.
- Being tested
- pamidronate disodium, arsenic trioxide, laboratory biomarker analysis, pharmacological study
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
pamidronate disodiumDrug
Also called Aminomux, APD, Aredia, GCP-23339A
Given IV
arsenic trioxideDrug
Also called Arsenic (III) Oxide, Arsenic Sesquioxide, Arsenous Acid Anhydride, AS2O3
Given IV
laboratory biomarker analysisOther
Correlative studies
Also called pharmacological studies
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (pamidronate disodium and arsenic trioxide) | Experimental | 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. Receives: Drug: pamidronate disodium; Drug: arsenic trioxide; Other: laboratory biomarker analysis; Other: pharmacological study |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 28 days
Secondary outcomes (2)
Survival
Measured: Up to 4 years
Time to failure
Measured: Up to 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2005 (estimated)
- Study startApr 2005
- Primary completionJun 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Refractory Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Przemyslaw Twardowski, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00124605
- Sponsor's protocol ID
- NCI-2012-03082
- Other IDs
- PHI-45, U01CA062505, CDR0000434807
- Status last verified
- Jan 2013
- First submitted
- 26 Jul 2005
- Last updated
- 7 Jan 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Jan 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Trial of Arsenic Trioxide in Combination With Pamidronate Disodium
- ClinicalTrials.gov ID
- NCT00124605
- Acronym / sponsor ID
- NCI-2012-03082
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Apr 2005
- Primary completion
- Jun 2009 (actual)
- First posted
- 28 Jul 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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.
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (pamidronate disodium and arsenic trioxide) | Experimental | Drug: pamidronate disodium, Drug: arsenic trioxide, Other: laboratory biomarker analysis, Other: pharmacological studyPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| pamidronate disodiumAlso: Aminomux, APD, Aredia, GCP-23339AGiven IV | Drug | Treatment (pamidronate disodium and arsenic trioxide) |
| arsenic trioxideAlso: Arsenic (III) Oxide, Arsenic Sesquioxide, Arsenous Acid Anhydride, AS2O3Given IV | Drug | Treatment (pamidronate disodium and arsenic trioxide) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (pamidronate disodium and arsenic trioxide) |
| pharmacological studyAlso: pharmacological studiesCorrelative studies | Other | Treatment (pamidronate disodium and arsenic trioxide) |
Primary outcome
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
Time frame: 28 days
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.
2 secondary outcomes
Survival
Time frame: Up to 4 years
Time to failure
Time frame: Up to 4 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jan 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Przemyslaw Twardowski principal investigator
City of Hope Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing pamidronate disodium, arsenic trioxide and laboratory biomarker analysis in people with Refractory Multiple Myeloma and Unspecified Adult Solid Tumor, Protocol Specific, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Jan 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary 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 (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jan 2013.