Multiple MyelomaPhase 1/2NCT00536575
Sorafenib and Bortezomib Treatment for Relapsed or Refractory Multiple Myeloma Patients
A Phase 1/2 study testing Bortezomib and Sorafenib in people with Multiple Myeloma, run by SCRI Development Innovations, LLC at 2 sites in United States.
Trial summary
This is a single-arm Phase I/II study of sorafenib and bortezomib with dose optimization in initial patients. The initial patients on the dose-finding portion of this study will be enrolled through a single institution. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Bortezomib and Sorafenib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 2 sitesUnited States
- Study dates
- Nov 2007to Aug 2010
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Eligible participants must have been previously diagnosed using standard criteria and have received no more than 2 prior regimens for the treatment of multiple myeloma.
- Participant must be defined as Relapsed or Refractory Disease by one of the following criteria prior to enrollment: Relapsed Disease after high-dose therapy (autologous stem cell transplantation) as part of the first-line line treatment program. These patients may have received a maximum of 1 previous regimen, Refractory Disease or Relapsed Disease after > 1 prior therapy for multiple myeloma. Prior bortezomib treatment permitted if the patient achieved a documented response.
- ECOG performance status 0, 1, or 2.
- WBC >= 3000; ANC >= 1000; platelets >= 50,000 (Patients with platelets >= 30,000 are eligible if thrombocytopenia is felt to be due to extensive bone marrow involvement with myeloma).
- Serum creatinine < 2.0 mg/dL for a calculated or measured creatinine clearance > 30 mL/minute
- Total bilirubin < 1.5 x ULN
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- ALT and AST < 2.5 x the ULN ( < 5 x ULN for patients with liver involvement)
- INR < 1.5 or a PT/PTT within normal limits. Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate. For patients on warfarin, the INR should be measured prior to initiation of sorafenib and monitored at least weekly, or as defined by the local standard of care, until INR is stable.
- Patients must have measurable or evaluable disease. In patients with disease limited to bone and bone marrow, serial paraprotein measurements are acceptable for evaluable disease.
Who cannot join
- Patients with > grade 1 peripheral neuropathy.
- Thrombolic or embolic events such as a cerebrovascular accident, including transient ischemic attacks, within the past 6 months.
- Pulmonary hemorrhage/bleeding event > CTCAE Grade 2 within 4 weeks of first dose of study drug.
- Any other hemorrhage/bleeding event > CTCAE Grade 3 within 4 weeks of first dose of study drug.
- Known brain metastasis. Patients with neurological symptoms must undergo CT scan/MRI of the brain to exclude brain metastasis.
- Patients with other medical conditions that would potentially interfere with their participation in this trial.
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- Patients with other active malignancies, or history of treatment for other invasive cancers, within 3 years of study entry.
- Patients with previous evidence of hypersensitivity to sorafenib, bortezomib, boron, or mannitol.
- Women who are pregnant or lactating are ineligible. All patients of childbearing potential are required to use adequate methods of contraception while receiving study treatment, and for at least 2 weeks after the last dose of sorafenib. Men should continue to use contraception until at least 3 months after their last dose of sorafenib.
- Evidence of POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome.
- Cardiac disease: Congestive heart failure > class II NYHA (see Appendix D.) Patients must not have unstable angina (anginal symptoms at rest), new onset angina (began within the last 3 months), or myocardial infarction within the past 6 months.
- Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
- Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management.
- Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C.
- Active clinically serious infection > CTCAE Grade 2.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Center for Cancer and Blood Disorders
Bethesda, Maryland, 20817
Tennessee Oncology, PLLC
Nashville, Tennessee, 37023
About this study
Official title: Phase I/II Trial of Sorafenib and Weekly Bortezomib in the Treatment of Patients With Relapsed or Refractory Multiple Myeloma
This is a single-arm Phase I/II study of sorafenib and bortezomib with dose optimization in initial patients. The initial patients on the dose-finding portion of this study will be enrolled through a single institution. Following establishment of the Phase II dose the study will open enrollment throughout the Sarah Cannon Research Institute (SCRI) Oncology Research Consortium.
The purpose of this study is to develop the combination of bortezomib (which is proven to be clinically active in patients with multiple myeloma) with sorafenib (a potent inhibitor of angiogenesis). This regimen will be developed in a schedule that is convenient for patients, and that is as minimally toxic to patients as possible.
Read the detailed description
Primary Objective:
To evaluate the efficacy of sorafenib with weekly bortezomib, as measured by objective response rate and progression-free survival in patients with relapsed/refractory multiple myeloma.
Secondary Objective:
To evaluate the feasibility and toxicity of sorafenib with weekly bortezomib in the treatment of patients with relapsed/refractory multiple myeloma.
- Conditions
- Multiple Myeloma
- Being tested
- Bortezomib, Sorafenib
- Keywords
- Multiple Myeloma, Relapsed, Refractory, Sorafenib, Bortezomib
- Medical subject headings
- Multiple Myeloma, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BortezomibDrug
Also called Velcade
Dose Level 1: Bortezomib 1.3mg/m2 IV bolus on days 1, 8, 15, and 22 of each 5-week cycle.
Dose Level 2: Bortezomib 1.6 mg/m2 IV bolus on days 1, 8, 15, and 22 of each 5-week cycle.
Dose Level 3: Bortezomib 1.6mg/m2 IV bolus on days 1, 8, 15, and 22 of each 5-week cycle.
SorafenibDrug
Also called Nexavar
Dose Levels 1 and 2: 200 mg by mouth twice daily
Dose Level 3: 400 mg by mouth twice daily
| Study group | Role | What they receive |
|---|---|---|
| Intervention | Experimental | The trial was designed as a single-arm Phase I/II study of sorafenib and bortezomib with dose optimization in initial patients. Phase I consisted of cohorts of 3 patients at each of three dose levels. Patients received bortezomib (Dose Level 1 - 1.3 mg/m2; Dose Level 2 - 1.6 mg/m2) by IV bolus on days 1, 8, 15, and 22 of each 5-week cycle with continuous oral dosing of sorafenib at 200 mg twice daily. Dose level 3 was planned as bortezomib 1.6 mg/m2 IV bolus on days 1, 8, 15, and 22 with sorafenib 400 mg by mouth twice daily throughout each 5-week cycle. Receives: Drug: Bortezomib; Drug: Sorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment
The percentage of patients who experience an objective benefit from treatment, determined by the treating physician after reviewing key laboratory values from blood and urine.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Sep 2007 (estimated)
- Study startNov 2007
- Primary completionFeb 2010
- Study completionAug 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- SCRI Development Innovations, LLC
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer
- Responsible party
- Sponsor
- Investigators
- Ian W. Flinn, M.D., Study chair, SCRI Development Innovations, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00536575
- Sponsor's protocol ID
- SCRI MM 14
- Status last verified
- Jan 2013
- First submitted
- 26 Sep 2007
- Last updated
- 27 Feb 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Trial of Sorafenib and Weekly Bortezomib in the Treatment of Patients With Relapsed or Refractory Multiple Myeloma
- ClinicalTrials.gov ID
- NCT00536575
- Acronym / sponsor ID
- SCRI MM 14
- Conditions
- Multiple Myeloma
- Keywords
- Multiple Myeloma, Relapsed, Refractory, Sorafenib, Bortezomib
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- SCRI Development Innovations, LLCUniversity, hospital or other
- Collaborators
- Bayer
- Study start
- Nov 2007
- Primary completion
- Feb 2010 (actual)
- Study completion
- Aug 2010 (actual)
- First posted
- 28 Sep 2007 (estimated)
- Results
- Posted 27 Feb 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a single-arm Phase I/II study of sorafenib and bortezomib with dose optimization in initial patients. The initial patients on the dose-finding portion of this study will be enrolled through a single institution. Following establishment of the Phase II dose the study will open enrollment throughout the Sarah Cannon Research Institute (SCRI) Oncology Research Consortium.
The purpose of this study is to develop the combination of bortezomib (which is proven to be clinically active in patients with multiple myeloma) with sorafenib (a potent inhibitor of angiogenesis). This regimen will be developed in a schedule that is convenient for patients, and that is as minimally toxic to patients as possible.
Detailed description
Primary Objective:
To evaluate the efficacy of sorafenib with weekly bortezomib, as measured by objective response rate and progression-free survival in patients with relapsed/refractory multiple myeloma.
Secondary Objective:
To evaluate the feasibility and toxicity of sorafenib with weekly bortezomib in the treatment of patients with relapsed/refractory multiple myeloma.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Intervention | Experimental | Drug: Bortezomib, Drug: SorafenibThe trial was designed as a single-arm Phase I/II study of sorafenib and bortezomib with dose optimization in initial patients. Phase I consisted of cohorts of 3 patients at each of three dose levels. Patients received bortezomib (Dose Level 1 - 1.3 mg/m2; Dose Level 2 - 1.6 mg/m2) by IV bolus on days 1, 8, 15, and 22 of each 5-week cycle with continuous oral dosing of sorafenib at 200 mg twice daily. Dose level 3 was planned as bortezomib 1.6 mg/m2 IV bolus on days 1, 8, 15, and 22 with sorafenib 400 mg by mouth twice daily throughout each 5-week cycle. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Eligible participants must have been previously diagnosed using standard criteria and have received no more than 2 prior regimens for the treatment of multiple myeloma.
- Participant must be defined as Relapsed or Refractory Disease by one of the following criteria prior to enrollment: Relapsed Disease after high-dose therapy (autologous stem cell transplantation) as part of the first-line line treatment program. These patients may have received a maximum of 1 previous regimen, Refractory Disease or Relapsed Disease after > 1 prior therapy for multiple myeloma. Prior bortezomib treatment permitted if the patient achieved a documented response.
- ECOG performance status 0, 1, or 2.
- WBC >= 3000; ANC >= 1000; platelets >= 50,000 (Patients with platelets >= 30,000 are eligible if thrombocytopenia is felt to be due to extensive bone marrow involvement with myeloma).
- Serum creatinine < 2.0 mg/dL for a calculated or measured creatinine clearance > 30 mL/minute
Key exclusion criteria (15 listed)
- Patients with > grade 1 peripheral neuropathy.
- Thrombolic or embolic events such as a cerebrovascular accident, including transient ischemic attacks, within the past 6 months.
- Pulmonary hemorrhage/bleeding event > CTCAE Grade 2 within 4 weeks of first dose of study drug.
- Any other hemorrhage/bleeding event > CTCAE Grade 3 within 4 weeks of first dose of study drug.
- Known brain metastasis. Patients with neurological symptoms must undergo CT scan/MRI of the brain to exclude brain metastasis.
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 |
|---|---|---|
| BortezomibAlso: VelcadeDose Level 1: Bortezomib 1.3mg/m2 IV bolus on days 1, 8, 15, and 22 of each 5-week cycle. Dose Level 2: Bortezomib 1.6 mg/m2 IV bolus on days 1, 8, 15, and 22 of each 5-week cycle. Dose Level 3: Bortezomib 1.6mg/m2 IV bolus on days 1, 8, 15, and 22 of each 5-week cycle. | Drug | Intervention |
| SorafenibAlso: NexavarDose Levels 1 and 2: 200 mg by mouth twice daily Dose Level 3: 400 mg by mouth twice daily | Drug | Intervention |
Primary outcome
Objective Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment
Time frame: 24 months
The percentage of patients who experience an objective benefit from treatment, determined by the treating physician after reviewing key laboratory values from blood and urine.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Sarah Cannon Research InstituteLink provided by the sponsor.
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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.
Ian W. Flinn, M.D. study chair
SCRI Development Innovations, LLC
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Bortezomib and Sorafenib in people with Multiple Myeloma, run by SCRI Development Innovations, LLC at 2 sites 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 9 inclusion and 15 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 27 Feb 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Feb 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Objective Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment (time frame: 24 months). 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 27 Feb 2013.