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Trial record 14 of 31 for:    IGFBP2

Topical Imiquimod and Abraxane in Treating Patients With Advanced Breast Cancer

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ClinicalTrials.gov Identifier: NCT00821964
Recruitment Status : Completed
First Posted : January 14, 2009
Results First Posted : June 28, 2017
Last Update Posted : January 2, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mary (Nora) Disis, University of Washington

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Male Breast Cancer
Recurrent Breast Cancer
Skin Metastases
Stage IV Breast Cancer
Interventions Drug: imiquimod
Drug: Abraxane
Other: laboratory biomarker analysis
Genetic: RNA analysis
Other: immunoenzyme technique
Enrollment 15
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Treatment (Biological Therapy, Chemo)
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Patients receive Abraxane IV over 30 minutes on days 1, 8, and 15 and apply topical imiquimod to cutaneous lesions QD on days 1-4, 8-11, 15-18, and 22-25. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.

imiquimod: Given topically

Abraxane: Given IV

laboratory biomarker analysis: Correlative studies

RNA analysis: Correlative studies

immunoenzyme technique: Correlative studies

Period Title: Overall Study
Started 15
Evaluable for Clinical Response 14
Evaluable for Pathologic Response 7
Completed 9
Not Completed 6
Arm/Group Title Treatment (Biological Therapy, Chemo)
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Patients receive Abraxane IV over 30 minutes on days 1, 8, and 15 and apply topical imiquimod to cutaneous lesions QD on days 1-4, 8-11, 15-18, and 22-25. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.

imiquimod: Given topically

Abraxane: Given IV

laboratory biomarker analysis: Correlative studies

RNA analysis: Correlative studies

immunoenzyme technique: Correlative studies

Overall Number of Baseline Participants 15
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants
<=18 years
0
   0.0%
Between 18 and 65 years
13
  86.7%
>=65 years
2
  13.3%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants
Female
15
 100.0%
Male
0
   0.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants
Hispanic or Latino
0
   0.0%
Not Hispanic or Latino
15
 100.0%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
13
  86.7%
More than one race
1
   6.7%
Unknown or Not Reported
1
   6.7%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 15 participants
15
 100.0%
1.Primary Outcome
Title Anti-tumor Effects of Imiquimod as Assessed by Modified World Health Organization (WHO) Criteria
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Tumor responses will be determined using the sum of the products of the largest perpendicular dimensions. Target lesions will be evaluated by the following response criteria: complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD).

Evaluation of target lesions per modified WHO response criteria:

  • Complete response (CR): complete clearance (100%) of target lesion(s)
  • Partial response (PR): ≥ 50% decrease in target lesion size
  • Stable disease (SD): < 50% decrease in target lesion size
  • Progressive (PD): ≥ 25% increase in target lesion size Overall Response Rate (ORR) determined at end of study treatment which was 1 week after cycle #3, unless patient was withdrawn from study. If patient was withdrawn from study, then ORR was determined after their last cycle of treatment received.
Time Frame Baseline and then every 4 weeks until week 24
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[Not Specified]
Arm/Group Title Treatment (Biological Therapy, Chemo)
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Patients receive Abraxane IV over 30 minutes on days 1, 8, and 15 and apply topical imiquimod to cutaneous lesions QD on days 1-4, 8-11, 15-18, and 22-25. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.

imiquimod: Given topically

Abraxane: Given IV

laboratory biomarker analysis: Correlative studies

RNA analysis: Correlative studies

immunoenzyme technique: Correlative studies

Overall Number of Participants Analyzed 14
Measure Type: Count of Participants
Unit of Measure: Participants
Total Evaluated in this Outcome Measure
14
 100.0%
Complete Response (CR)
5
  35.7%
Partial Response (PR)
5
  35.7%
Stable Disease (SD)
3
  21.4%
Progressive Disease (PD)
1
   7.1%
2.Primary Outcome
Title Safety and Systemic Toxicity as Assessed by a Review of Medical History, Physical Exam, Systems, Performance Status, and Clinical Labs (CBC and CMP)
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Evaluated according to the Cancer Therapy Evaluation Program (CTEP) Common Terminology Criteria for Adverse Events (CTCAE) v3.0 and monitoring of adverse events will be done per Food and Drug Administration (FDA) and National Cancer Institute (NCI) guidelines for the time frame below.

Number of Participants with at Least 1 Adverse Event as Assessed by a Review of Medical History, Physical Exam, Systems, Performance Status, and Clinical Labs (CBC and CMP) under the following CTCAE categories:

Constitutional (Fatigue) Neurological (Neuropathy (sensory or motor)) Cardiac (Arrhythemia) Pulmonary (Cough, Pharyngitis) GI (Constipation, Diarrhea, Mucositis, Vomiting) Dermatology (Ulceration, Hairloss/alopecia) Pain (Headache, other pain) Syndrome (Flu-like) Visual Changes Hearing/Auditory Edema Other (General)

In addition they were asked the severity of the event so that a clinician could grade the event.

Time Frame Baseline and weeks 5, 9 13, 16, 20, and 24
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Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment (Biological Therapy, Chemo)
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Patients receive Abraxane IV over 30 minutes on days 1, 8, and 15 and apply topical imiquimod to cutaneous lesions QD on days 1-4, 8-11, 15-18, and 22-25. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.

imiquimod: Given topically

Abraxane: Given IV

laboratory biomarker analysis: Correlative studies

RNA analysis: Correlative studies

immunoenzyme technique: Correlative studies

Overall Number of Participants Analyzed 15
Measure Type: Count of Participants
Unit of Measure: Participants
15
 100.0%
3.Primary Outcome
Title Pathologic Response by Immunohistochemical (IHC)as Assessed by Skin Punch Biopsy of the Target Lesion
Hide Description This is done by IHC staining reviewed by a pathologist. This is done by comparing the baseline to the post-treatment biopsy tissue. Yes equals absence of residual disease.
Time Frame Pre-and post-treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment (Biological Therapy, Chemo)
Hide Arm/Group Description:

Patients receive Abraxane IV over 30 minutes on days 1, 8, and 15 and apply topical imiquimod to cutaneous lesions QD on days 1-4, 8-11, 15-18, and 22-25. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.

imiquimod: Given topically

Abraxane: Given IV

laboratory biomarker analysis: Correlative studies

RNA analysis: Correlative studies

immunoenzyme technique: Correlative studies

Overall Number of Participants Analyzed 7
Measure Type: Count of Participants
Unit of Measure: Participants
Total Number of Evaluable for Pathologic Response
7
 100.0%
Evaluable Pts. with Pathologic Response Post Tx
5
  71.4%
Evaluable Pts. without Pathologic Response Post Tx
2
  28.6%
4.Secondary Outcome
Title Endogenous Immunity to Common Breast Tumor Antigens (HER2, IGFBP-2, Topoisomerase II-alpha, and p53) in Peripheral Blood as Assessed by IFN-gamma and ELISPOT Assay
Hide Description Peripheral blood will be obtained at baseline, after cycle 3 (end of study treatment) and at week 24 (end of study) to assess the immune response. A positive antigen-specific T cell immune response will be defined as a T cell precursor frequency more robust than 1:20,000 PBMC if the patients did not have a detectable response prior to treatment. In patients with a pre-existent immune response, the development of an immune response twice baseline will constitute augmentation.
Time Frame Baseline and at weeks 13 and 24
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Hide Analysis Population Description
[Not Specified]
Arm/Group Title HER2, IGFBP-2, MAGE3, TopoIIa Antigen - Baseline to Week 13 HER2, IGFBP-2, MAGE3, Topo IIa Antigen - Baseline to Week 24
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Precursor frequency of HER2, IGFBP-2, MAGE3, Topo II-alpha antigens between baseline to Week 13
Precursor frequency of HER2, IGFBP-2, MAGE3, Topo IIa Antigen - Baseline to Week 24
Overall Number of Participants Analyzed 8 3
Measure Type: Count of Participants
Unit of Measure: Participants
HER2 Antigen Positive antigen-specific T cell immune response
0
   0.0%
0
   0.0%
Negative antigen specific T cell immune response
8
 100.0%
3
 100.0%
IGFBP-2 Antigen Positive antigen-specific T cell immune response
2
  25.0%
1
  33.3%
Negative antigen specific T cell immune response
6
  75.0%
2
  66.7%
MAGE3 Antigen Positive antigen-specific T cell immune response
5
  62.5%
1
  33.3%
Negative antigen specific T cell immune response
3
  37.5%
2
  66.7%
TopoII-alpha Antigen Positive antigen-specific T cell immune response
2
  25.0%
0
   0.0%
Negative antigen specific T cell immune response
6
  75.0%
3
 100.0%
5.Secondary Outcome
Title Incidence of Reduction of Serum TGF-beta Levels as Assessed by ELISA and Correlation With Th1 Adaptive Immunity and Clinical Response
Hide Description Incidence of reduction of serum TGF-beta levels as assessed by ELISA and correlation with Th1 adaptive immunity and clinical response is defined as a reduction of at least 25% from baseline value to the value measured at week 13.
Time Frame Baseline and at weeks 13
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[Not Specified]
Arm/Group Title Incidence of Reduction of TGF-beta Levels
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Incidence of reduction of serum TGF-beta levels assessed by ELISA of at least 25% from baseline to week 13
Overall Number of Participants Analyzed 8
Measure Type: Count of Participants
Unit of Measure: Participants
No incidence of 25% reduction of TGF-beta at week1
8
 100.0%
Incidence of 25% reduction of TGF-beta at week 13
0
   0.0%
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Treatment (Biological Therapy, Chemo)
Hide Arm/Group Description

Patients receive Abraxane IV over 30 minutes on days 1, 8, and 15 and apply topical imiquimod to cutaneous lesions QD on days 1-4, 8-11, 15-18, and 22-25. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.

imiquimod: Given topically

Abraxane: Given IV

laboratory biomarker analysis: Correlative studies

RNA analysis: Correlative studies

immunoenzyme technique: Correlative studies

All-Cause Mortality
Treatment (Biological Therapy, Chemo)
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Treatment (Biological Therapy, Chemo)
Affected / at Risk (%) # Events
Total   1/15 (6.67%)    
General disorders   
Pain  1  1/15 (6.67%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Treatment (Biological Therapy, Chemo)
Affected / at Risk (%) # Events
Total   15/15 (100.00%)    
Blood and lymphatic system disorders   
Other - Low HCT  1  11/15 (73.33%)  23
Other - High immature granulocytes  1  7/15 (46.67%)  13
Other - Low immuature granulocytes  1  1/15 (6.67%)  1
Other - High MCH  1  1/15 (6.67%)  1
Other - Low MCHC  1  4/15 (26.67%)  8
Other High MCV  1  3/15 (20.00%)  8
Other - High monocytes  1  1/15 (6.67%)  2
Other - Low RBC  1  8/15 (53.33%)  14
Others - High RDWCV  1  4/15 (26.67%)  5
Anemia  1  13/15 (86.67%)  28
Lymphopenia  1  11/15 (73.33%)  23
Leukocytes High  1  1/15 (6.67%)  1
Leukopenia  1  13/15 (86.67%)  37
Neutropenia  1  8/15 (53.33%)  17
Thrombocytopenia  1  2/15 (13.33%)  2
Cardiac disorders   
Hypertension  1  1/15 (6.67%)  1
Eye disorders   
Ocular/Visual Other  1 [1]  1/15 (6.67%)  1
Blurred Vision  1  1/15 (6.67%)  1
Gastrointestinal disorders   
Weight Loss  1  1/15 (6.67%)  1
Constipation  1  4/15 (26.67%)  7
Diarrhea  1  4/15 (26.67%)  6
Mucositis/Stomatitis  1 [2]  3/15 (20.00%)  3
Mucositis/Stromatitis  1 [3]  2/15 (13.33%)  2
Nausea  1  7/15 (46.67%)  13
Vomiting  1  4/15 (26.67%)  11
Distension/Bloating, abdominal  1  1/15 (6.67%)  1
General disorders   
Fatigue  1  7/15 (46.67%)  12
Sweating (diaphoresis)  1  1/15 (6.67%)  1
Nail Changes  1  1/15 (6.67%)  1
Axilla (right), shoulder, lateral back  1  1/15 (6.67%)  1
Pain - Chest, Noncardiac  1  1/15 (6.67%)  1
Infections and infestations   
Beta-Hemolytic Streptococcus Bacteria  1  1/15 (6.67%)  1
Renal Pyelonephritis  1  1/15 (6.67%)  1
Upper Respiratory Infection  1  1/15 (6.67%)  1
Injury, poisoning and procedural complications   
Seroma Axillary on Right Side  1  1/15 (6.67%)  1
Investigations   
ANC/AGC High  1  2/15 (13.33%)  2
Alkaline Phosphatase  1 [4]  3/15 (20.00%)  3
ALT/ SGPT High  1  2/15 (13.33%)  2
AST/SGOT High  1  1/15 (6.67%)  2
AST/SGOT Low  1  1/15 (6.67%)  1
Creatinine High  1  1/15 (6.67%)  1
Creatinine Low  1  1/15 (6.67%)  1
GFR Low  1 [5]  1/15 (6.67%)  1
BUN High  1 [5]  3/15 (20.00%)  3
BUN Low  1  2/15 (13.33%)  2
Chloride High  1  2/15 (13.33%)  2
Ion gap high  1  1/15 (6.67%)  1
Protein Low  1  2/15 (13.33%)  2
Axilla (left)  1  1/15 (6.67%)  1
Metabolism and nutrition disorders   
Anorexia  1  8/15 (53.33%)  11
Dehydration  1  1/15 (6.67%)  1
Hyperkalemia  1  1/15 (6.67%)  2
Hypoalbuminemia  1  5/15 (33.33%)  6
Hypocalcemia  1  1/15 (6.67%)  3
Hypokalemia  1  5/15 (33.33%)  6
Hyponatremia  1  1/15 (6.67%)  1
Musculoskeletal and connective tissue disorders   
Arthralgia  1  1/15 (6.67%)  2
Pain - Back  1  1/15 (6.67%)  1
Myalgia  1  2/15 (13.33%)  2
Pain (unspecified)  1  3/15 (20.00%)  10
Shoulder (right) - muscular/bony  1  1/15 (6.67%)  1
Nervous system disorders   
Dizziness  1  3/15 (20.00%)  3
Neuropathy: Motor  1  2/15 (13.33%)  2
Neuropathy: Sensory  1  9/15 (60.00%)  13
Headache  1  6/15 (40.00%)  9
Reproductive system and breast disorders   
Pain - Breast  1  1/15 (6.67%)  1
Respiratory, thoracic and mediastinal disorders   
Nose Bleeds  1  1/15 (6.67%)  2
Dyspnea  1  6/15 (40.00%)  10
Cough  1  2/15 (13.33%)  2
Skin and subcutaneous tissue disorders   
Hair Loss/Alopecia (scalp or body)  1  11/15 (73.33%)  12
Pruritus/Itching  1  1/15 (6.67%)  2
Rash/Desquamation  1  3/15 (20.00%)  7
Rash: Acne/Acneiform  1  1/15 (6.67%)  1
Rash: Hand-Foot Skin Reaction  1  1/15 (6.67%)  1
Psoriasis-like rash  1  1/15 (6.67%)  1
Vascular disorders   
Edema: Limb  1  2/15 (13.33%)  3
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
[1]
Eye redness, swelling, mild scleral edema
[2]
Clinical Exam
[3]
Functional/Symptomatic
[4]
High
[5]
Not clinically significant
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Principal Investigator
Organization: University of Washington
Responsible Party: Mary (Nora) Disis, University of Washington
ClinicalTrials.gov Identifier: NCT00821964     History of Changes
Other Study ID Numbers: 6578
NCI-2010-00040 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
R01CA138521 ( U.S. NIH Grant/Contract )
131 ( Other Identifier: Tumor Vaccine Group )
First Submitted: January 13, 2009
First Posted: January 14, 2009
Results First Submitted: April 14, 2017
Results First Posted: June 28, 2017
Last Update Posted: January 2, 2018