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Refractory Chronic Lymphocytic LeukemiaPhase 1NCT00303797

Sorafenib and Bortezomib in Treating Patients With Advanced Cancer

A Phase 1 study testing 17-N-allylamino-17-demethoxygeldanamycin/bortezomib and sorafenib tosylate in people with Refractory Chronic Lymphocytic Leukemia and Refractory Multiple Myeloma, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This phase I trial is studying the side effects and best dose of sorafenib and bortezomib in treating patients with advanced cancer. Sorafenib and bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
17-N-allylamino-17-demethoxygeldanamycin/bortezomib and sorafenib tosylate
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
1 siteUnited States
Study dates
Dec 2005to May 2010
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

  • Diagnosis of 1 of the following:
  • Cytologically or histologically proven unresectable solid tumor for which no curative treatment options exist (group I - dose-escalation phase)
  • Multiple myeloma or chronic lymphocytic leukemia requiring treatment (group II - maximum tolerated dose phase)
  • Failed ≥ 1 prior regimen
  • Non-secretory myeloma allowed
  • No known standard therapy that is potentially curative or definitely capable of extending life expectancy exists
Show all 41Show fewer
  • Tumor amenable to serial sampling (group II)
  • ECOG performance status 0-2
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Hemoglobin ≥ 9 g/dL
  • Platelet count ≥ 100,000/mm^3 (75,000/mm^3 for patients with multiple myeloma [group II])
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • AST ≤ 3 times ULN (5 times ULN if liver involvement)
  • Creatinine ≤ 1.5 times ULN (2.5 times ULN for patients with multiple myeloma [group II])
  • Life expectancy ≥ 12 weeks
  • No uncontrolled infection
  • No New York Heart Association class III or IV heart disease
  • No uncontrolled hypertension, labile hypertension, or history of poor compliance with antihypertensive medication
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No sensory peripheral neuropathy of any etiology > grade 1 or neuropathic pain of any etiology
  • No active HIV infection requiring therapy
  • No inability to swallow that would preclude use of oral medications
  • No evidence of bleeding diathesis
  • Medically capable and willing to provide biologic specimens as required (mandatory for patients in group II)
  • Priorbortezomib allowed
  • More than 3 weeks since prior chemotherapy (6 weeks for mitomycin C or nitrosoureas) and recovered
  • More than 4 weeks since prior immunotherapy or biologic therapy
  • More than 2 weeks since prior steroid therapy (group II only)
  • No prior anti-vascular endothelial growth factor therapy
  • More than 4 weeks since prior full-field radiotherapy (2 weeks for limited-field radiotherapy)
  • No prior radiation to > 25% of bone marrow
  • More than 4 weeks since major surgery (e.g., laparotomy) (2 weeks for minor surgery)
  • Insertion of a vascular access device is not considered major or minor surgery
  • No concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary other therapy considered investigational
  • No concurrent prophylactic colony-stimulating factors
  • No concurrent therapeutic anticoagulation
  • Concurrent prophylactic anticoagulation (i.e., low-dose warfarin) of venous or arterial access devices allowed provided requirements for PT, INR, or PTT are met
  • No concurrent cytochrome P450 enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine, and phenobarbital), rifampin, or Hypericum perforatum (St. John's Wort)
  • No concurrent participation in any other study involving a pharmacologic agent (e.g., drugs, biologics, immunotherapy, or gene therapy), either for symptom control, or therapeutic intent

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Mayo Clinic

    Rochester, Minnesota, 55905

Other trials in United States

About this study

Official title: A Phase I Study of the Raf Kinase/VEGFR Inhibitor BAY 43-9006 in Combination With the Proteasome Inhibitor PS-341 in Patients With Advanced Malignancies

This phase I trial is studying the side effects and best dose of sorafenib and bortezomib in treating patients with advanced cancer. Sorafenib and bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Sorafenib may also stop the growth of cancer cells by blocking blood flow to the cancer

Read the detailed description

OBJECTIVES:

  1. To determine the maximum tolerated dose (MTD) of sorafenib and bortezomib in patients with advanced malignancies.

II. To describe the toxicities associated with the combination of sorafenib and bortezomib.

III. To evaluate the therapeutic antitumor activity of the combination of sorafenib and bortezomib.

IV. To evaluate the effects of sorafenib on the disposition of bortezomib.

OUTLINE: This is a dose-escalation study. Patients are assigned to 1 of 2 groups according to disease type.

GROUP I (solid tumors-dose-escalation group): Patients receive oral sorafenib twice daily on days 1-21 and bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of sorafenib and bortezomib until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

GROUP II (multiple myeloma or chronic lymphocytic leukemia-maximum tolerated dose [MTD] group): Patients receive oral sorafenib at the MTD twice daily on days 3-21 of course 1 and on days 1-21 of each subsequent course. Patients also receive bortezomib IV over 3-5 seconds at the MTD on days 1, 4, 8, and 11.

Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed for 3 months.

Being tested
17-N-allylamino-17-demethoxygeldanamycin/bortezomib, sorafenib tosylate
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell, Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 17-N-allylamino-17-demethoxygeldanamycin/bortezomibDrug

  • sorafenib tosylateDrug

    Also called BAY 43-9006, BAY 43-9006 Tosylate Salt, BAY 54-9085, Nexavar

Study groups in NCT00303797
Study groupRoleWhat they receive
Treatment (bortezomib, sorafenib tosylate)ExperimentalGROUP I (solid tumors-dose-escalation group): Patients receive oral sorafenib twice daily on days 1-21 and bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of sorafenib and bortezomib until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. GROUP II (multiple myeloma or chronic lymphocytic leukemia-maximum tolerated dose [MTD] group): Patients receive oral sorafenib at the MTD twice daily on days 3-21 of course 1 and on days 1-21 of each subsequent course. Patients also receive bortezomib IV over 3-5 seconds at the MTD on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: 17-N-allylamino-17-demethoxygeldanamycin/bortezomib; Drug: sorafenib tosylate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. MTD as assessed by the number of patients with dose-limiting toxicity (DLT) using Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0)

    DLTs include: Hematologic: Grade 4 ANC for ≥5 days, Grade 4 anemia of any duration, or PLT <25,000 of any duration; Renal: Serum creatinine ≥2 times baseline or > 2x upper limit of normal if baseline levels normal; All other non-hematologic toxicities ≥grade 3 as per CTCAE v3.0 except fatigue; Any toxicities that caused dose delay of > 2 weeks of the intended next dose.

    MTD is the dose level below the lowest dose that induces DLT in at least one-third of patients (2 of 6 patients).

    Measured: Observed for at least 3 weeks at a given dose level combination

  2. Toxicity as assessed by CTCAE v3.0

    Non-hematologic toxicities will be evaluated via the ordinal CTC standard toxicity grading. Hematologic toxicity measures of thrombocytopenia, neutropenia, and leukopenia will be assessed using continuous variables as the outcome measures (primarily nadir) as well as categorization via Common Toxicity Criteria standard grading.

    Overall toxicity incidence as well as toxicity profiles by dose level, patient and tumor site will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.

    Measured: Observed for at least 3 weeks at a given dose level combination

  3. Antitumor activity as assessed by tumor measurement or evaluation of indicator lesion by computed tomography (CT) or magnetic resonance imaging (MRI)

    Measured: Baseline, prior to each course (every 3 weeks) during dose escalation, every 6 weeks for solid tumors, and confirmatory scans at least 4 weeks following initial documentation of objective response

  4. Effects of sorafenib on the disposition of bortezomib

    Up to 20 patients with hematologic malignancies will be treated at the MTD to evaluate markers of drug activity and pharmacokinetics of this combination.

    Measured: From cohort II registration prior to each course

Secondary outcomes (4)

  1. Tumor response as assessed by CT or MRI using modified Response Evaluation Criteria in Solid Tumors (RECIST)

    CLL Modified RECIST:

    Measurable lesions: lesions that can be accurately measured in at least one dimension with longest diameter > 20 mm. With spiral CT scan, lesion must be > 10 mm in at least one dimension. Target lesions (up to 3) should be selected and a sum of the longest diameter (LD) for all will be the baseline sum LD. Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least 30% decrease in the sum of the longest diameter (LD) of target lesion taking as reference the baseline sum LD.

    Measured: Baseline, every 3 weeks during dose escalation, every 6 weeks for solid tumors, and confirmatory scans at least 4 weeks following initial documentation of objective response

  2. Best overall response as assessed using modified RECIST

    CLL Progression (PD): As least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

    Measured: Baseline until disease progression/recurrence

  3. Duration of overall response

    Myeloma CR = Disappearance of M-protein from serum and urine, Bone marrow biopsy ≤5% plasma cells, No increase in lytic bone lesions, and Disappearance of soft tissue plasmacytomas. Patients who meet some, but not all, the criteria are classified as VGPR. Myeloma PR = 50-89% reduction of M-protein in serum and reduction of ≥90% or to <200 mg in 24-hour urinary light chain excretion (patients with non-secretory myeloma: a ≥50% reduction in plasma cells in a bone marrow aspirate), ≥50% reduction in soft tissue plasmacytoma, and No increase in number or size of lytic bone lesions.

    Measured: From the time measurement criteria are met for CR/PR (whichever is first recorded) until the first date recurrent or progressive disease is documented

  4. Duration of stable disease

    Myeloma PD: Increase of M-protein >25% above the lowest response level in serum or urine (absolute increase of at least 0.5 g/dL serum or 200 mg/24 hours urine); Patients with non-secretory myeloma: an increase in bone marrow plasmacytosis by 25% above the lowest remission value (absolute increase at least 10% bone marrow plasma cells); New soft tissue plasmacytomas or increase in size by 50% (and at least 1 cm); New lytic bone lesions or increase in the size of the existing bone lesions by 50% (and at least 1 cm); Development of hypercalcemia serum calcium >11.5 mg/dL.

    Measured: From the start of the treatment until the criteria for progression are met

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Mar 2006 (estimated)
  2. Study startDec 2005
  3. Primary completionMay 2010

Resources

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
50 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00303797
Sponsor's protocol ID
NCI-2009-00124
Other IDs
MC0511, U01CA069912
Status last verified
Mar 2013
First submitted
15 Mar 2006
Last updated
19 Mar 2013
Results posted
No

Publications

  • Kumar SK, Jett J, Marks R, Richardson R, Quevedo F, Moynihan T, Croghan G, Markovic SN, Bible KC, Qin R, Tan A, Molina J, Kaufmann SH, Erlichman C, Adjei AA. Phase 1 study of sorafenib in combination with bortezomib in patients with advanced malignancies. Invest New Drugs. 2013 Oct;31(5):1201-6. doi: 10.1007/s10637-013-0004-2. Epub 2013 Jul 26.

    PubMed 23887852

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing 17-N-allylamino-17-demethoxygeldanamycin/bortezomib and sorafenib tosylate in people with Refractory Chronic Lymphocytic Leukemia and Refractory Multiple Myeloma, 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 41 inclusion and 0 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 19 Mar 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 as assessed by the number of patients with dose-limiting toxicity (DLT) using Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0) (time frame: Observed for at least 3 weeks at a given dose level combination). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00303797, which also lists 1 linked publication.

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 19 Mar 2013.

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