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Nelfinavir Mesylate in Treating Patients With Recurrent, Metastatic, or Unresectable Liposarcoma

Sponsor
City of Hope Medical Center (Other)
Overall Status
Terminated
CT.gov ID
NCT00233948
Collaborator
(none)
29
Enrollment
2
Locations
1
Arm
14.5
Patients Per Site

Study Details

Study Description

Brief Summary

RATIONALE: Antiviral drugs, such as nelfinavir mesylate, may help prevent cancer cells from spreading.

PURPOSE: This phase I/II trial is studying the side effects and best dose of nelfinavir mesylate and to see how well it works in treating patients with recurrent, metastatic, or unresectable liposarcoma.

Condition or Disease Intervention/Treatment Phase
  • Drug: nelfinavir mesylate
  • Procedure: biopsy
  • Other: laboratory biomarker analysis
  • Other: pharmacological study
  • Genetic: gene expression analysis
  • Genetic: western blotting
  • Genetic: reverse transcriptase-polymerase chain reaction
  • Other: immunoenzyme technique
 Phase 1/Phase 2

Detailed Description

OBJECTIVES:

  1. To assess the toxicity and tolerance of nelfinavir in patients with liposarcoma.

  2. To define the maximum tolerated dose (MTD) of nelfinavir when given daily as a single agent and to describe the toxicities at each does studied.

  3. To evaluate the pharmacokinetics of nelfinavir. IV. To assess the response rate and progression free survival in patients with liposarcoma treated with nelfinavir.

  4. To evaluate the expression and activity of certain proteins in the tumors of patients entered on this study, which may be important to the cytotoxicity of nelfinavir (SREBP-1, p21, NFkB (NFkappaB), caspase 3).

OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.

Patients receive oral nelfinavir mesylate twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Study Design

Study Type:
Interventional
Actual Enrollment :
29 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I/II Study of Nelfinavir in Liposarcoma
Study Start Date :
Mar 1, 2006
Actual Primary Completion Date :
Jul 1, 2013

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm I

Patients receive oral nelfinavir mesylate twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: nelfinavir mesylate
Given orally
Other Names:
  • Viracept

    • Procedure: biopsy
    Correlative studies
    Other Names:
  • biopsies

    • Other: laboratory biomarker analysis
    Correlative studies

    Other: pharmacological study
    Correlative studies
    Other Names:
  • pharmacological studies

    • Genetic: gene expression analysis
    Correlative studies

    Genetic: western blotting
    Correlative studies
    Other Names:
  • Blotting, Western
  • Western Blot

    • Genetic: reverse transcriptase-polymerase chain reaction
    Correlative studies
    Other Names:
  • RT-PCR

    • Other: immunoenzyme technique
    Correlative studies
    Other Names:
  • immunoenzyme techniques

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Dose Limiting Toxicity (DLT) (Phase I) [4 weeks from start of treatment, up to 2 years]

      DLT is defined as any grade III toxicity not reversible to grade II or less within one week, or any grade IV toxicity. Hyperlipidemia, hyperglycemia, nausea, vomiting and diarrhea are not DLTs unless they are uncontrolled grade 3/4. Dose delays lasting more than 2 weeks due to toxicity are considered a DLT. Dose escalation schedule for nelfinavir: 1250 mg bid ; 1500 mg bid; 2125 mg bid; 3000 mg bid; 4250 mg bid ; 6000 mg bid ; 8500 mg bid ; 12000 mg bid

    2. Maximum Tolerated Dose (MTD) (Phase I) [4 weeks from start of treatment, up to 2 years]

      The highest dose tested in which fewer than 33% of patients experience an attributable DLT to the study drug, when at least 6 patients are treated at that dose and are evaluable for toxicity. If PK analysis of 3 patients treated at 4250 mg bid and 3 patients at 3000 mg bid confirms that the first dose area under the curve and Cmax of nelfinavir does not increase appreciably at doses greater than 1875 mg BID then 3000 mg BID will be deemed the MTD.

    3. Overall Response Rate (Phase II) [After 3 cycles of treatment, up to 2 years.]

      Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    Inclusion

    • Patients must have histologically confirmed liposarcoma, which is recurrent, metastatic or unresectable

    • There is no limit to prior chemotherapy regimens; in addition, patients may have prior radiation

    • All patients must have measurable disease, defined as lesions that can be accurately measured in at least one dimension (>= 20 mm with conventional techniques or >= 10mm with spiral CT scan); pleural effusions and ascites will not be considered measurable, but may be present in addition to the measurable lesion(s)

    • ECOG (Eastern Cooperative Oncology Group) performance status of 0, 1, or 2; patients should have an expected survival of at least 3 months

    • Absolute neutrophil count >= 1,000/ul

    • Platelets >= 75000/ul

    • Total bilirubin =< 2.0 g/dl

    • AST(SGOT)/ALT(SGPT) =< 2.0X institutional upper limit of normal

    • Brain metastasis is not an exclusion; however, patients are only eligible if they have had successful control of the brain tumor(s) by surgery or radiation therapy

    • All prior therapy must have been completed at least 3 weeks prior to the patient's entry on this trial

    • No concurrent chemotherapy, radiotherapy, immunotherapy or other investigational agents

    • Women of child-bearing potential and men must agree to use adequate contraception (barrier method of birth control) prior to study entry and for the duration of study participation; should a women become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

    • Ability to understand and willingness to sign a written informed consent document

    Exclusion

    • Patient has had prior treatment with or is currently taking a protease inhibitor

    • Patients enrolled cannot be on the following medications: cisapride, triazolam, midazolam, ergot derivatives, amiodarone, quinidine, dihydropyridine calcium antagonists (amlodipine, felodipine, isradipine, nicardipine, nifedipine, nimodipine, and nisoldipine), sildenafil, dilantin, rifampin or oral contraceptives

    • Uncontrolled intercurrent illness

    • Patients must have recovered from any expected toxicities of previous chemotherapy or radiation therapy

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 City of Hope Medical Center Duarte California United States 91010
    2 South Pasadena Cancer Center Pasadena California United States 91030

    Sponsors and Collaborators

    • City of Hope Medical Center

    Investigators

    • Principal Investigator: Warren Chow, City of Hope Medical Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    City of Hope Medical Center
    ClinicalTrials.gov Identifier:
    NCT00233948
    Other Study ID Numbers:
    • 04090
    • NCI-2010-01263
    • CDR0000438712
    • FDA R01FD003006-03
    First Posted:
    Oct 6, 2005
    Last Update Posted:
    Apr 1, 2015
    Last Verified:
    Mar 1, 2015
    Additional relevant MeSH terms:
    Sarcoma
    Liposarcoma
    Nelfinavir

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Phase I: Dose Level 1 Phase I: Dose Level II Phase I: Dose Level III Phase I: Dose Level IV Phase I: Dose Level V Phase II
    Arm/Group Description Oral Nelfinavir at 1250mg bid. Oral Nelfinavir at 1500mg bid. Oral Nelfinavir at 2125mg bid. Oral Nelfinavir at 3000mg bid. Oral Nelfinavir at 4250mg bid. Oral Nelfinavir at 3000mg bid
    Period Title: Overall Study
    STARTED 4 3 3 3 4 12
    COMPLETED 3 3 3 3 4 12
    NOT COMPLETED 1 0 0 0 0 0

    Baseline Characteristics

    Arm/Group Title Phase I Phase II Total
    Arm/Group Description Phase I dose escalation portion of the study. Initial dose of oral Nelfinavir was 1250 mg bid with escalation to the MTD at 4250 mg bid using a standard 3+3 dose escalation scheme. Oral Nelfinavir at 3000 mg bid Total of all reporting groups
    Overall Participants 17 12 29
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    64
    63
    64
    Sex: Female, Male (Count of Participants)
    Female
    6
    35.3%
    6
    50%
    12
    41.4%
    Male
    11
    64.7%
    6
    50%
    17
    58.6%
    Region of Enrollment (participants) [Number]
    United States
    17
    100%
    12
    100%
    29
    100%

    Outcome Measures

    1. Primary Outcome
    Title Dose Limiting Toxicity (DLT) (Phase I)
    Description DLT is defined as any grade III toxicity not reversible to grade II or less within one week, or any grade IV toxicity. Hyperlipidemia, hyperglycemia, nausea, vomiting and diarrhea are not DLTs unless they are uncontrolled grade 3/4. Dose delays lasting more than 2 weeks due to toxicity are considered a DLT. Dose escalation schedule for nelfinavir: 1250 mg bid ; 1500 mg bid; 2125 mg bid; 3000 mg bid; 4250 mg bid ; 6000 mg bid ; 8500 mg bid ; 12000 mg bid
    Time Frame 4 weeks from start of treatment, up to 2 years

    Outcome Measure Data

    Analysis Population Description
    All patients receiving treatment were evaluated for DLT.
    Arm/Group Title Phase I: Dose Level I Phase I: Dose Level II Phase I: Dose Level III Phase I: Dose Level IV Phase I: Dose Level V
    Arm/Group Description Oral Nelfinavir at 1250mg bid. Oral Nelfinavir at 1500mg bid. Oral Nelfinavir at 2125mg bid. Oral Nelfinavir at 3000mg bid. Oral Nelfinavir at 4250mg bid.
    Measure Participants 4 3 3 3 4
    Number [participants with DLTs]
    0
    0%
    0
    0%
    0
    0%
    0
    NaN
    0
    NaN
    2. Primary Outcome
    Title Maximum Tolerated Dose (MTD) (Phase I)
    Description The highest dose tested in which fewer than 33% of patients experience an attributable DLT to the study drug, when at least 6 patients are treated at that dose and are evaluable for toxicity. If PK analysis of 3 patients treated at 4250 mg bid and 3 patients at 3000 mg bid confirms that the first dose area under the curve and Cmax of nelfinavir does not increase appreciably at doses greater than 1875 mg BID then 3000 mg BID will be deemed the MTD.
    Time Frame 4 weeks from start of treatment, up to 2 years

    Outcome Measure Data

    Analysis Population Description
    All patients observed for 28 days while receiving a full course of therapy or who experienced a DLT. Patients withdrawing before completion of the first course, for reasons other than DLT, were replaced.
    Arm/Group Title Phase I
    Arm/Group Description All patients enrolled on the Phase I (dose-finding) portion of the study.
    Measure Participants 17
    Number [mg]
    3000
    3. Primary Outcome
    Title Overall Response Rate (Phase II)
    Description Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
    Time Frame After 3 cycles of treatment, up to 2 years.

    Outcome Measure Data

    Analysis Population Description
    Patients who complete 3 cycles of treatment or who terminate treatment for reasons of toxicity, or who progress prior to the completion of 3 cycles of therapy on the Phase II portion of the study.
    Arm/Group Title Phase II
    Arm/Group Description Oral Nelfinavir at 3000 mg bid
    Measure Participants 12
    Number [participants]
    1
    5.9%

    Adverse Events

    Time Frame Adverse events were recorded over a period of 5 years, 2 months.
    Adverse Event Reporting Description "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
    Arm/Group Title Phase I: Dose Level I Phase I: Dose Level II Phase I: Dose Level III Phase I: Dose Level IV Phase I: Dose Level V Phase II
    Arm/Group Description Oral Nelfinavir at 1250mg bid. Oral Nelfinavir at 1500mg bid. Oral Nelfinavir at 2125mg bid. Oral Nelfinavir at 3000mg bid. Oral Nelfinavir at 4250mg bid. Oral Nelfinavir at 3000 mg bid
    All Cause Mortality
    Phase I: Dose Level I Phase I: Dose Level II Phase I: Dose Level III Phase I: Dose Level IV Phase I: Dose Level V Phase II
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Phase I: Dose Level I Phase I: Dose Level II Phase I: Dose Level III Phase I: Dose Level IV Phase I: Dose Level V Phase II
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/4 (50%) 0/3 (0%) 2/3 (66.7%) 1/3 (33.3%) 0/4 (0%) 2/12 (16.7%)
    Gastrointestinal disorders
    Diarrhea 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 1/12 (8.3%) 1
    Nausea 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 1/12 (8.3%) 1
    Pancreatitis 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 0/12 (0%) 0
    General disorders
    Disease progression 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/4 (0%) 0 1/12 (8.3%) 1
    Fatigue 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 2/12 (16.7%) 2
    Infections and infestations
    Urinary tract infection 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 1/12 (8.3%) 1
    Investigations
    Alanine aminotransferase increased 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 1/12 (8.3%) 2
    Aspartate aminotransferase increased 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 1/12 (8.3%) 2
    Metabolism and nutrition disorders
    Acidosis 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 0/12 (0%) 0
    Nervous system disorders
    Depressed level of consciousness 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 0/12 (0%) 0
    Encephalopathy 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 2 0/3 (0%) 0 0/4 (0%) 0 0/12 (0%) 0
    Psychiatric disorders
    Confusion 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 2 0/3 (0%) 0 0/4 (0%) 0 0/12 (0%) 0
    Insomnia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 1/12 (8.3%) 1
    Respiratory, thoracic and mediastinal disorders
    Dyspnea 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/4 (0%) 0 1/12 (8.3%) 1
    Hypoxia 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 0/12 (0%) 0
    Respiratory disorder 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 0/12 (0%) 0
    Other (Not Including Serious) Adverse Events
    Phase I: Dose Level I Phase I: Dose Level II Phase I: Dose Level III Phase I: Dose Level IV Phase I: Dose Level V Phase II
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 4/4 (100%) 3/3 (100%) 3/3 (100%) 3/3 (100%) 4/4 (100%) 12/12 (100%)
    Blood and lymphatic system disorders
    Blood disorder 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 2 0/3 (0%) 0 0/4 (0%) 0 0/12 (0%) 0
    Hemoglobin decreased 1/4 (25%) 1 1/3 (33.3%) 2 2/3 (66.7%) 4 1/3 (33.3%) 1 3/4 (75%) 6 8/12 (66.7%) 54
    Lymphatic disorder 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/4 (0%) 0 0/12 (0%) 0
    Cardiac disorders
    Arrhythmia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 3/12 (25%) 3
    Cardiac disorder 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 1/12 (8.3%) 6
    Palpitations 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/4 (25%) 1 1/12 (8.3%) 1
    Premature ventricular contractions 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/4 (0%) 0 0/12 (0%) 0
    Sinus tachycardia 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/4 (0%) 0 2/12 (16.7%) 2
    Ventricular tachycardia 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/4 (0%) 0 0/12 (0%) 0
    Eye disorders
    Vision blurred 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 1/12 (8.3%) 3
    Gastrointestinal disorders
    Abdominal distension 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 2 0/3 (0%) 0 0/4 (0%) 0 1/12 (8.3%) 4
    Abdominal pain 2/4 (50%) 6 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/4 (25%) 2 7/12 (58.3%) 8
    Ascites 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/4 (0%) 0 0/12 (0%) 0
    Constipation 1/4 (25%) 2 0/3 (0%) 0 1/3 (33.3%) 2 1/3 (33.3%) 1 0/4 (0%) 0 4/12 (33.3%) 14
    Diarrhea 4/4 (100%) 13 1/3 (33.3%) 1 3/3 (100%) 6 3/3 (100%) 8 4/4 (100%) 11 10/12 (83.3%) 48
    Dry mouth 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 2 0/3 (0%) 0 0/4 (0%) 0 1/12 (8.3%) 3
    Dysphagia 1/4 (25%) 1 1/3 (33.3%) 2 1/3 (33.3%) 2 0/3 (0%) 0 0/4 (0%) 0 1/12 (8.3%) 1
    Ear, nose and throat examination abnormal 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/4 (25%) 1 0/12 (0%) 0
    Esophageal stenosis 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 0/12 (0%) 0
    Fecal incontinence 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 2 0/3 (0%) 0 0/4 (0%) 0 0/12 (0%) 0
    Flatulence 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 1/12 (8.3%) 2
    Gastritis 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 1/12 (8.3%) 1
    Gastrointestinal disorder 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 1/12 (8.3%) 1
    Nausea 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 2 1/3 (33.3%) 1 3/4 (75%) 5 5/12 (41.7%) 6
    Rectal hemorrhage 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/4 (25%) 1 0/12 (0%) 0
    Stomach pain 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/4 (25%) 1 1/12 (8.3%) 1
    Vomiting 2/4 (50%) 2 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 1/4 (25%) 1 6/12 (50%) 8
    General disorders
    Chest pain 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 2/12 (16.7%) 2
    Chills 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 1/12 (8.3%) 1
    Disease progression 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/4 (0%) 0 0/12 (0%) 0
    Edema limbs 1/4 (25%) 1 0/3 (0%) 0 2/3 (66.7%) 3 0/3 (0%) 0 1/4 (25%) 1 3/12 (25%) 3
    Fatigue 1/4 (25%) 3 1/3 (33.3%) 1 2/3 (66.7%) 4 1/3 (33.3%) 1 2/4 (50%) 2 9/12 (75%) 21
    Fever 0/4 (0%) 0 1/3 (33.3%) 1 1/3 (33.3%) 1 1/3 (33.3%) 1 0/4 (0%) 0 3/12 (25%) 5
    Pain 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 2/3 (66.7%) 2 0/4 (0%) 0 4/12 (33.3%) 9
    Infections and infestations
    Bronchitis 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 0/12 (0%) 0
    Infection 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 1/12 (8.3%) 1
    Infection, Bacterial (COH) 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/4 (0%) 0 0/12 (0%) 0
    Sepsis 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 2 0/3 (0%) 0 0/4 (0%) 0 0/12 (0%) 0
    Skin infection 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 1/12 (8.3%) 1
    Spinal cord infection 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 1/12 (8.3%) 1
    Upper respiratory infection 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 0/12 (0%) 0
    Injury, poisoning and procedural complications
    Bruising 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 1/12 (8.3%) 1
    Dermatitis radiation 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 1/12 (8.3%) 1
    Investigations
    Activated partial thromboplastin time prolonged 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 1/12 (8.3%) 1
    Alanine aminotransferase increased 2/4 (50%) 4 0/3 (0%) 0 1/3 (33.3%) 1 1/3 (33.3%) 4 3/4 (75%) 10 2/12 (16.7%) 4
    Alkaline phosphatase increased 2/4 (50%) 2 0/3 (0%) 0 1/3 (33.3%) 2 1/3 (33.3%) 1 4/4 (100%) 9 5/12 (41.7%) 11
    Aspartate aminotransferase increased 2/4 (50%) 4 0/3 (0%) 0 2/3 (66.7%) 2 1/3 (33.3%) 3 3/4 (75%) 7 4/12 (33.3%) 11
    Bilirubin increased 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 1/12 (8.3%) 1
    Creatine phosphokinase increased 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/4 (25%) 3 0/12 (0%) 0
    Creatinine increased 2/4 (50%) 2 1/3 (33.3%) 1 1/3 (33.3%) 1 0/3 (0%) 0 0/4 (0%) 0 2/12 (16.7%) 14
    Hypercholesterolemia 1/4 (25%) 2 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 0/12 (0%) 0
    Laboratory test abnormal 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/4 (0%) 0 0/12 (0%) 0
    Leukocyte count decreased 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 2/3 (66.7%) 8 1/4 (25%) 6 3/12 (25%) 25
    Leukopenia 2/4 (50%) 2 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 0/12 (0%) 0
    Lipase increased 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 0/12 (0%) 0
    Lymphocyte count decreased 0/4 (0%) 0 1/3 (33.3%) 1 1/3 (33.3%) 2 1/3 (33.3%) 4 1/4 (25%) 3 8/12 (66.7%) 20
    Neutrophil count decreased 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 1/3 (33.3%) 5 1/4 (25%) 2 2/12 (16.7%) 13
    Platelet count decreased 1/4 (25%) 1 1/3 (33.3%) 1 0/3 (0%) 0 2/3 (66.7%) 8 0/4 (0%) 0 4/12 (33.3%) 10
    Serum cholesterol increased 0/4 (0%) 0 1/3 (33.3%) 12 0/3 (0%) 0 1/3 (33.3%) 4 3/4 (75%) 5 6/12 (50%) 46
    Weight gain 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 1/12 (8.3%) 1
    Weight loss 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 1/3 (33.3%) 1 0/4 (0%) 0 1/12 (8.3%) 1
    Metabolism and nutrition disorders
    Anorexia 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 2 1/3 (33.3%) 1 0/4 (0%) 0 8/12 (66.7%) 17
    Blood bicarbonate decreased 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/4 (25%) 1 0/12 (0%) 0
    Blood glucose increased 0/4 (0%) 0 1/3 (33.3%) 1 1/3 (33.3%) 1 2/3 (66.7%) 4 1/4 (25%) 2 5/12 (41.7%) 11
    Blood uric acid increased 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 1/12 (8.3%) 1
    Dehydration 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/4 (0%) 0 1/12 (8.3%) 1
    Hyperglycemia 1/4 (25%) 3 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 0/12 (0%) 0
    Hypoalbuminemia 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 0/12 (0%) 0
    Hypocalcemia 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 0/12 (0%) 0
    Hyponatremia 2/4 (50%) 2 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 0/12 (0%) 0
    Hypophosphatemia 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 0/12 (0%) 0
    Serum albumin decreased 0/4 (0%) 0 1/3 (33.3%) 2 1/3 (33.3%) 2 0/3 (0%) 0 2/4 (50%) 5 4/12 (33.3%) 5
    Serum calcium decreased 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/4 (0%) 0 2/12 (16.7%) 2
    Serum calcium increased 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 2 0/3 (0%) 0 0/4 (0%) 0 3/12 (25%) 6
    Serum glucose decreased 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/4 (0%) 0 3/12 (25%) 8
    Serum magnesium increased 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 2/12 (16.7%) 4
    Serum phosphate decreased 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 1/12 (8.3%) 1
    Serum potassium decreased 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 2 0/3 (0%) 0 1/4 (25%) 3 3/12 (25%) 4
    Serum potassium increased 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/4 (0%) 0 2/12 (16.7%) 7
    Serum sodium decreased 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 3 0/3 (0%) 0 1/4 (25%) 2 7/12 (58.3%) 18
    Serum sodium increased 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 1/12 (8.3%) 1
    Serum triglycerides increased 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 3 1/4 (25%) 3 6/12 (50%) 11
    Musculoskeletal and connective tissue disorders
    Arthritis 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 1/12 (8.3%) 1
    Back pain 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 1/4 (25%) 2 6/12 (50%) 7
    Bone pain 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 1/12 (8.3%) 1
    Muscle weakness 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 2 0/3 (0%) 0 0/4 (0%) 0 1/12 (8.3%) 2
    Muscle weakness upper limb 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/4 (0%) 0 0/12 (0%) 0
    Musculoskeletal disorder 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/4 (0%) 0 0/12 (0%) 0
    Myalgia 1/4 (25%) 1 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/4 (0%) 0 0/12 (0%) 0
    Pain in extremity 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/4 (25%) 1 1/12 (8.3%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Myelodysplasia 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 0/12 (0%) 0
    Tumor pain 0/4 (0%) 0 0/3 (0%) 0 2/3 (66.7%) 6 1/3 (33.3%) 1 0/4 (0%) 0 0/12 (0%) 0
    Nervous system disorders
    Dizziness 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/4 (25%) 1 2/12 (16.7%) 2
    Headache 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/4 (0%) 0 2/12 (16.7%) 2
    Peripheral motor neuropathy 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/4 (25%) 1 0/12 (0%) 0
    Peripheral sensory neuropathy 0/4 (0%) 0 2/3 (66.7%) 2 0/3 (0%) 0 1/3 (33.3%) 2 0/4 (0%) 0 1/12 (8.3%) 1
    Syncope 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 1/12 (8.3%) 1
    Tremor 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 2 0/3 (0%) 0 0/4 (0%) 0 1/12 (8.3%) 1
    Psychiatric disorders
    Agitation 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 1/12 (8.3%) 1
    Anxiety 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 1/3 (33.3%) 1 1/4 (25%) 1 1/12 (8.3%) 2
    Depression 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 3/12 (25%) 4
    Insomnia 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 2 1/3 (33.3%) 1 1/4 (25%) 1 2/12 (16.7%) 4
    Psychosis 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 1/12 (8.3%) 1
    Renal and urinary disorders
    Bladder pain 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/4 (0%) 0 0/12 (0%) 0
    Glomerular filtration rate decreased 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 1/4 (25%) 2 0/12 (0%) 0
    Protein urine positive 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 2 0/3 (0%) 0 0/4 (0%) 0 1/12 (8.3%) 1
    Urinary frequency 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 1/4 (25%) 2 1/12 (8.3%) 1
    Urinary incontinence 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 2 0/3 (0%) 0 0/4 (0%) 0 0/12 (0%) 0
    Urogenital disorder 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/4 (0%) 0 0/12 (0%) 0
    Reproductive system and breast disorders
    Breast pain 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 1/12 (8.3%) 2
    Erectile dysfunction 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 1/12 (8.3%) 3
    Gynecomastia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 1/12 (8.3%) 1
    Pelvic pain 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 1/12 (8.3%) 1
    Respiratory, thoracic and mediastinal disorders
    Allergic rhinitis 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 1/4 (25%) 1 1/12 (8.3%) 1
    Cough 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/4 (25%) 4 3/12 (25%) 3
    Dyspnea 0/4 (0%) 0 1/3 (33.3%) 2 1/3 (33.3%) 2 1/3 (33.3%) 2 0/4 (0%) 0 2/12 (16.7%) 2
    Hypoxia 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 1/3 (33.3%) 1 0/4 (0%) 0 0/12 (0%) 0
    Nasal congestion 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 2/12 (16.7%) 2
    Pharyngolaryngeal pain 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/4 (0%) 0 1/12 (8.3%) 1
    Pleural effusion 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/4 (0%) 0 0/12 (0%) 0
    Respiratory disorder 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 1/3 (33.3%) 1 0/4 (0%) 0 2/12 (16.7%) 2
    Voice alteration 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 2 0/3 (0%) 0 0/4 (0%) 0 0/12 (0%) 0
    Skin and subcutaneous tissue disorders
    Pruritus 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 1/12 (8.3%) 1
    Rash desquamating 0/4 (0%) 0 1/3 (33.3%) 1 1/3 (33.3%) 2 0/3 (0%) 0 1/4 (25%) 1 1/12 (8.3%) 1
    Skin disorder 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 2 0/3 (0%) 0 1/4 (25%) 1 2/12 (16.7%) 3
    Skin hyperpigmentation 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 1/12 (8.3%) 7
    Sweating 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 1/12 (8.3%) 1
    Vascular disorders
    Hemorrhage 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/4 (25%) 1 0/12 (0%) 0
    Hypotension 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 2 0/3 (0%) 0 0/4 (0%) 0 0/12 (0%) 0
    Phlebitis 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 0/12 (0%) 0

    Limitations/Caveats

    After 12 patients were accrued to the Phase II portion, the study was terminated…protocol objectives for the Phase II portion not met. Closed prematurely due to drug availability issues.

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Paul Frankel, Ph.D.
    Organization City of Hope
    Phone 626-256-4673 ext 65265
    Email pfrankel@coh.org
    Responsible Party:
    City of Hope Medical Center
    ClinicalTrials.gov Identifier:
    NCT00233948
    Other Study ID Numbers:
    • 04090
    • NCI-2010-01263
    • CDR0000438712
    • FDA R01FD003006-03
    First Posted:
    Oct 6, 2005
    Last Update Posted:
    Apr 1, 2015
    Last Verified:
    Mar 1, 2015