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Trial record 4 of 31 for:    "Breast Ductal Carcinoma" | "Bone Density Conservation Agents"

4-Hydroxytamoxifen or Tamoxifen Citrate in Treating Women With Newly Diagnosed Ductal Breast Carcinoma in Situ

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00952731
Recruitment Status : Completed
First Posted : August 6, 2009
Results First Posted : July 21, 2015
Last Update Posted : July 21, 2015
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Seema Khan, Northwestern University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Ductal Breast Carcinoma in Situ
Estrogen Receptor-positive Breast Cancer
Interventions Drug: oral placebo
Drug: afimoxifene
Drug: tamoxifen citrate
Drug: placebo gel
Enrollment 27
Recruitment Details Between November 2009 and July 2011, subjects were recruited at Northwestern University and Washington University. The original accrual goal was 112, however, the study was halted early due to drug supply issues.
Pre-assignment Details A total of 31 subjects were registered to the study but only 27 were randomized and began the study. Three participants were deemed ineligible and 1 withdrew consent before randomization.
Arm/Group Title Treatment Gel + Oral Placebo Placebo Gel + Oral Treatment
Hide Arm/Group Description

4-hydroxytamoxifen gel 2mg/breast applied daily. Oral placebo taken daily.

oral placebo: Oral placebo taken daily for 4-10 weeks.

afimoxifene: 2mg/breast applied daily in the form of a gel for 4-10 weeks.

Placebo gel applied to the breasts daily. 20mg oral tamoxifen taken daily (taken as two (2) 10mg capsules).

tamoxifen citrate: 20mg oral tamoxifen taken daily (taken as two (2) 10mg capsules) for 4-10 weeks.

placebo gel: Placebo gel applied to breasts daily for 4-10 weeks.

Period Title: Overall Study
Started 13 14
Randomization 13 14
Treatment & Pre-Surgery 12 14
Surgery 12 14
Follow-up 12 14
Completed 12 14
Not Completed 1 0
Reason Not Completed
Drug supply expired             1             0
Arm/Group Title Treatment Gel + Oral Placebo Placebo Gel + Oral Treatment Total
Hide Arm/Group Description

4-hydroxytamoxifen gel 2mg/breast applied daily. Oral placebo taken daily.

oral placebo: Oral placebo taken daily for 4-10 weeks.

afimoxifene: 2mg/breast applied daily in the form of a gel for 4-10 weeks.

Placebo gel applied to the breasts daily. 20mg oral tamoxifen taken daily (taken as two (2) 10mg capsules).

tamoxifen citrate: 20mg oral tamoxifen taken daily (taken as two (2) 10mg capsules) for 4-10 weeks.

placebo gel: Placebo gel applied to breasts daily for 4-10 weeks.

Total of all reporting groups
Overall Number of Baseline Participants 13 14 27
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 13 participants 14 participants 27 participants
40-49 years 1 2 3
50-59 years 4 7 11
60-69 years 6 4 10
70-79 years 0 1 1
80-89 years 2 0 2
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 14 participants 27 participants
Female
13
 100.0%
14
 100.0%
27
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 14 participants 27 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
1
   7.7%
0
   0.0%
1
   3.7%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
4
  30.8%
7
  50.0%
11
  40.7%
White
8
  61.5%
6
  42.9%
14
  51.9%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
1
   7.1%
1
   3.7%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 13 participants 14 participants 27 participants
13 14 27
Menopausal status  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 13 participants 14 participants 27 participants
Pre-Menopausal 4 3 7
Post-Menopausal 9 11 20
1.Primary Outcome
Title Difference Between Ki-67 Labeling Index in Tissue Samples Taken at Baseline and Post-treatment
Hide Description Ki-67 was measured in matched core and excision tissue samples containing DCIS (Ductal Carcinoma In-Situ) lesions, the core sample was at baseline while the excision sample was at surgery (after approximately 4-10 weeks of treatment).
Time Frame Baseline and after 4-10 weeks of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
18 total subjects were evaluable for immunohistochemistry marker testing including the Ki-67 labeling index. Of the 26 participants who completed study treatment 2 did not have matching samples available for testing and 6 were excluded because of insufficient DCIS lesion in their samples for testing.
Arm/Group Title Treatment Gel + Oral Placebo Placebo Gel + Oral Treatment
Hide Arm/Group Description:

4-hydroxytamoxifen gel 2mg/breast applied daily. Oral placebo taken daily.

oral placebo: Oral placebo taken daily for 4-10 weeks.

afimoxifene: 2mg/breast applied daily in the form of a gel for 4-10 weeks.

Placebo gel applied to the breasts daily. 20mg oral tamoxifen taken daily (taken as two (2) 10mg capsules).

tamoxifen citrate: 20mg oral tamoxifen taken daily (taken as two (2) 10mg capsules) for 4-10 weeks.

placebo gel: Placebo gel applied to breasts daily for 4-10 weeks.

Overall Number of Participants Analyzed 9 9
Mean (Standard Deviation)
Unit of Measure: percentage of 300 DCIS cells
-3.4  (5.0) -5.1  (5.5)
2.Secondary Outcome
Title Difference in Mean Score for Vasomotor Symptoms Including Hot Flashes From Baseline to Time of Surgery
Hide Description Hot flashes were assessed by the Breast Cancer Prevention Trial Eight Symptom Scale (BESS) questionnaire. This questionnaire measures the incidence of a number of symptoms by asking participants how frequently they experienced them on a scale of 0-4 (0 being Not at All and 4 being Extremely often). BESS questionnaire was administered at baseline and time of surgery. The incidence of vasomotor symptoms (including hot flashes, night sweats, and cold sweats) was measured at baseline (Day 0) and end of treatment prior to surgery (at least 4 weeks later or up to 10 weeks, depending on scheduled surgery date), and changes in the mean score for hot flashes were observed.
Time Frame Baseline and after 4-10 weeks of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
1 patient who did not complete the treatment period due expired drug supply was not evaluable for this outcome measure.
Arm/Group Title Treatment Gel + Oral Placebo Placebo Gel + Oral Treatment
Hide Arm/Group Description:

4-hydroxytamoxifen gel 2mg/breast applied daily. Oral placebo taken daily.

oral placebo: Oral placebo taken daily for 4-10 weeks.

afimoxifene: 2mg/breast applied daily in the form of a gel for 4-10 weeks.

Placebo gel applied to the breasts daily. 20mg oral tamoxifen taken daily (taken as two (2) 10mg capsules).

tamoxifen citrate: 20mg oral tamoxifen taken daily (taken as two (2) 10mg capsules) for 4-10 weeks.

placebo gel: Placebo gel applied to breasts daily for 4-10 weeks.

Overall Number of Participants Analyzed 12 14
Mean (Standard Deviation)
Unit of Measure: units on a scale
0.33  (0.64) 0.55  (1.05)
3.Secondary Outcome
Title Difference in vWF Coagulation Protein in Blood Collected at Baseline and Just Prior to Surgery
Hide Description The difference between vWF coagulation protein in blood samples collected at baseline and before surgery were measured using the immune-turbidimetric assay.
Time Frame Baseline to immediately before surgery (after approximately 4-10 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
1 patient who did not complete the treatment period due expired drug supply was not evaluable for this outcome measure.
Arm/Group Title Treatment Gel + Oral Placebo Placebo Gel + Oral Treatment
Hide Arm/Group Description:

4-hydroxytamoxifen gel 2mg/breast applied daily. Oral placebo taken daily.

oral placebo: Oral placebo taken daily for 4-10 weeks.

afimoxifene: 2mg/breast applied daily in the form of a gel for 4-10 weeks.

Placebo gel applied to the breasts daily. 20mg oral tamoxifen taken daily (taken as two (2) 10mg capsules).

tamoxifen citrate: 20mg oral tamoxifen taken daily (taken as two (2) 10mg capsules) for 4-10 weeks.

placebo gel: Placebo gel applied to breasts daily for 4-10 weeks.

Overall Number of Participants Analyzed 12 14
Mean (Standard Deviation)
Unit of Measure: percentage of vWF protein in blood
-2.6  (52.3) 51.2  (71.0)
4.Secondary Outcome
Title Difference in Factor VIII Coagulation Protein in Blood Collected at Baseline and Just Prior to Surgery
Hide Description The difference between Factor VIII coagulation protein in blood samples collected at baseline and before surgery was measured with VisuLize antigen ELISA Kits.
Time Frame Baseline and immediately before surgery (after approximately 4-10 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
1 patient who did not complete the treatment period due expired drug supply was not evaluable for this outcome measure.
Arm/Group Title Treatment Gel + Oral Placebo Placebo Gel + Oral Treatment
Hide Arm/Group Description:

4-hydroxytamoxifen gel 2mg/breast applied daily. Oral placebo taken daily.

oral placebo: Oral placebo taken daily for 4-10 weeks.

afimoxifene: 2mg/breast applied daily in the form of a gel for 4-10 weeks.

Placebo gel applied to the breasts daily. 20mg oral tamoxifen taken daily (taken as two (2) 10mg capsules).

tamoxifen citrate: 20mg oral tamoxifen taken daily (taken as two (2) 10mg capsules) for 4-10 weeks.

placebo gel: Placebo gel applied to breasts daily for 4-10 weeks.

Overall Number of Participants Analyzed 12 14
Mean (Standard Deviation)
Unit of Measure: percentage Factor VIII protein in blood
8.7  (18.5) 11.6  (17.3)
5.Secondary Outcome
Title Difference in Factor IX Coagulation Protein in Blood Collected at Baseline and Just Prior to Surgery
Hide Description The difference between Factor IX coagulation protein in blood samples collected at baseline and before surgery was measured with VisuLize antigen ELISA Kits.
Time Frame Baseline and immediately before surgery (after approximately 4-10 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
1 patient who did not complete the treatment period due expired drug supply was not evaluable for this outcome measure.
Arm/Group Title Treatment Gel + Oral Placebo Placebo Gel + Oral Treatment
Hide Arm/Group Description:

4-hydroxytamoxifen gel 2mg/breast applied daily. Oral placebo taken daily.

oral placebo: Oral placebo taken daily for 4-10 weeks.

afimoxifene: 2mg/breast applied daily in the form of a gel for 4-10 weeks.

Placebo gel applied to the breasts daily. 20mg oral tamoxifen taken daily (taken as two (2) 10mg capsules).

tamoxifen citrate: 20mg oral tamoxifen taken daily (taken as two (2) 10mg capsules) for 4-10 weeks.

placebo gel: Placebo gel applied to breasts daily for 4-10 weeks.

Overall Number of Participants Analyzed 12 14
Mean (Standard Deviation)
Unit of Measure: percentage of Factor IX protein in blood
-5.6  (13.6) 0.4  (10.2)
6.Secondary Outcome
Title Difference in Protein S Coagulation Protein in Blood Collected at Baseline and Just Prior to Surgery
Hide Description The difference between protein S coagulation protein in blood samples collected at baseline and before surgery was measured using an ELISA Kit.
Time Frame Baseline and immediately before surgery (after approximately 4-10 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
1 patient who did not complete the treatment period due expired drug supply was not evaluable for this outcome measure.
Arm/Group Title Treatment Gel + Oral Placebo Placebo Gel + Oral Treatment
Hide Arm/Group Description:

4-hydroxytamoxifen gel 2mg/breast applied daily. Oral placebo taken daily.

oral placebo: Oral placebo taken daily for 4-10 weeks.

afimoxifene: 2mg/breast applied daily in the form of a gel for 4-10 weeks.

Placebo gel applied to the breasts daily. 20mg oral tamoxifen taken daily (taken as two (2) 10mg capsules).

tamoxifen citrate: 20mg oral tamoxifen taken daily (taken as two (2) 10mg capsules) for 4-10 weeks.

placebo gel: Placebo gel applied to breasts daily for 4-10 weeks.

Overall Number of Participants Analyzed 12 14
Mean (Standard Deviation)
Unit of Measure: percentage of protein S in blood
-1.6  (6.5) -2.7  (9.3)
7.Other Pre-specified Outcome
Title Compare Concentrations of Tamoxifen and Its Metabolites (4-hydroxytamoxifen, Endoxifen, N-desmethyl Tamoxifen (NDT)) Obtained From Samples on the Day of Surgery
Hide Description Concentrations of tamoxifen and its metabolites: 4-hydroxytamoxifen, endoxifen, and NDT were measured in breast tissue, blood, and Nipple Aspirate Fluid (NAF) that was collected on the day of surgery.
Time Frame Day of surgery (after approximately 4-10 weeks)
Outcome Measure Data Not Reported
8.Other Pre-specified Outcome
Title Drug Metabolite Levels in the Two Study Groups by CYP2D6 Polymorphism Status
Hide Description Descriptive statistics and confidence intervals will be provided.
Time Frame 28-70 days
Outcome Measure Data Not Reported
9.Other Pre-specified Outcome
Title 4-OHT Affects Known Tamoxifen-modulated Pathways
Hide Description Descriptive statistics and confidence intervals will be provided.
Time Frame 28-70 days
Outcome Measure Data Not Reported
10.Other Pre-specified Outcome
Title TAM Metabolite Concentrations and Estrogen Response Markers in Nipple Aspiration Fluid (NAF)
Hide Description Descriptive statistics and confidence intervals will be provided.
Time Frame 28-70 days
Outcome Measure Data Not Reported
11.Other Pre-specified Outcome
Title E and Z 4-OHT Isomers
Hide Description Descriptive statistics and confidence intervals will be provided.
Time Frame 28-70 days
Outcome Measure Data Not Reported
Time Frame 14 weeks
Adverse Event Reporting Description Patients were asked about any adverse events they may have experienced at every study visit.
 
Arm/Group Title Treatment Gel + Oral Placebo Placebo Gel + Oral Treatment
Hide Arm/Group Description

4-hydroxytamoxifen gel 2mg/breast applied daily. Oral placebo taken daily.

oral placebo: Oral placebo taken daily for 4-10 weeks.

afimoxifene: 2mg/breast applied daily in the form of a gel for 4-10 weeks.

Placebo gel applied to the breasts daily. 20mg oral tamoxifen taken daily (taken as two (2) 10mg capsules).

tamoxifen citrate: 20mg oral tamoxifen taken daily (taken as two (2) 10mg capsules) for 4-10 weeks.

placebo gel: Placebo gel applied to breasts daily for 4-10 weeks.

All-Cause Mortality
Treatment Gel + Oral Placebo Placebo Gel + Oral Treatment
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Treatment Gel + Oral Placebo Placebo Gel + Oral Treatment
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/12 (0.00%)      0/14 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Treatment Gel + Oral Placebo Placebo Gel + Oral Treatment
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   12/12 (100.00%)      14/14 (100.00%)    
Blood and lymphatic system disorders     
Sweating (Diaphoresis)  1  4/12 (33.33%)  10 6/14 (42.86%)  30
Edema  1  2/12 (16.67%)  2 1/14 (7.14%)  1
Hemorrhage, Gu::Vagina  1  0/12 (0.00%)  0 1/14 (7.14%)  1
Cardiac disorders     
Hypertension  1  0/12 (0.00%)  0 1/14 (7.14%)  1
Endocrine disorders     
Insomnia  1  3/12 (25.00%)  1/14 (7.14%)  1
Fatigue  1  4/12 (33.33%)  4 5/14 (35.71%)  6
Hot Flashes  1  7/12 (58.33%)  13 7/14 (50.00%)  26
Eye disorders     
Vision-blurred vision  1  0/12 (0.00%)  0 1/14 (7.14%)  2
Gastrointestinal disorders     
Anorexia  1  1/12 (8.33%)  1 2/14 (14.29%)  2
Constipation  1  1/12 (8.33%)  1 4/14 (28.57%)  4
Diarrhea  1  2/12 (16.67%)  3 1/14 (7.14%)  1
Dry Mouth  1  0/12 (0.00%)  0 3/14 (21.43%)  3
Heartburn/Dyspepsia  1  1/12 (8.33%)  1 2/14 (14.29%)  5
Nausea  1  0/12 (0.00%)  0 3/14 (21.43%)  3
Vomiting  1  0/12 (0.00%)  0 1/14 (7.14%)  1
General disorders     
Pain  1  5/12 (41.67%)  5 0/14 (0.00%)  0
Flu -like Syndromes  1  1/12 (8.33%)  1 0/14 (0.00%)  0
Pain: Other  1  0/12 (0.00%)  0 2/14 (14.29%)  2
Pain: Back  1  0/12 (0.00%)  0 1/14 (7.14%)  1
Pain: Chest/Thorax Nos  1  0/12 (0.00%)  0 1/14 (7.14%)  1
Pain: Extremity/Limb  1  0/12 (0.00%)  0 2/14 (14.29%)  4
Pain: Headache  1  0/12 (0.00%)  0 6/14 (42.86%)  8
Pain: Pain: Nos  1  0/12 (0.00%)  0 1/14 (7.14%)  1
Pain: Pain: Stomach  1  0/12 (0.00%)  0 1/14 (7.14%)  1
Pain: Throat/Pharynx/Larynx  1  0/12 (0.00%)  0 3/14 (21.43%)  3
Immune system disorders     
Fever  1  0/12 (0.00%)  0 1/14 (7.14%)  1
Infections and infestations     
Infection- Other  1  0/12 (0.00%)  0 3/14 (21.43%)  3
Infection with unknown ANC  1  2/12 (16.67%)  2 1/14 (7.14%)  1
Metabolism and nutrition disorders     
Weight Gain  1  3/12 (25.00%)  3 1/14 (7.14%)  1
Metabolic/Laboratory - Other  1  0/12 (0.00%)  0 1/14 (7.14%)  1
Nervous system disorders     
Neuropathy  1  0/12 (0.00%)  0 1/14 (7.14%)  1
Mood Alteration  1  1/12 (8.33%)  1 3/14 (21.43%)  3
Dizziness  1  0/12 (0.00%)  0 3/14 (21.43%)  3
Cognitive Disturbance  1  1/12 (8.33%)  1 1/14 (7.14%)  1
Memory Impairment  1  1/12 (8.33%)  1 0/14 (0.00%)  0
Tremor  1  1/12 (8.33%)  1 0/14 (0.00%)  0
Renal and urinary disorders     
Incontinence  1  0/12 (0.00%)  0 3/14 (21.43%)  3
Reproductive system and breast disorders     
Vaginitis (not due to infection)  1  0/12 (0.00%)  0 1/14 (7.14%)  1
Vaginal discharge (not infectious)  1  0/12 (0.00%)  0 2/14 (14.29%)  2
Sexual/Reproductive Function - Other  1  0/12 (0.00%)  0 1/14 (7.14%)  2
Irregular Menses  1  0/12 (0.00%)  0 1/14 (7.14%)  1
Pain: Breast  1  5/12 (41.67%)  7 9/14 (64.29%)  12
Pain: Vagina  1  1/12 (8.33%)  1 0/14 (0.00%)  0
Vaginal Dryness  1  2/12 (16.67%)  2 0/14 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Nasal Cavity/Paranasal Sinus Reactions  1  0/12 (0.00%)  0 3/14 (21.43%)  4
Voice change/dysarthria  1  0/12 (0.00%)  0 1/14 (7.14%)  1
Dyspnea (shorntess of breath)  1  0/12 (0.00%)  0 1/14 (7.14%)  1
Cough  1  0/12 (0.00%)  0 5/14 (35.71%)  6
Pain: Chest Wall  1  1/12 (8.33%)  2 1/14 (7.14%)  1
Skin and subcutaneous tissue disorders     
Nail changes  1  0/12 (0.00%)  0 1/14 (7.14%)  1
Wound complication, non-infectious  1  0/12 (0.00%)  0 1/14 (7.14%)  1
Pruritus/Itching  1  2/12 (16.67%)  3 0/14 (0.00%)  0
Rash/desquamation  1  1/12 (8.33%)  1 0/14 (0.00%)  0
Dermatology/Skin - Other  1  1/12 (8.33%)  1 0/14 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE Version 3.0
The study was originally designed to enroll 112 participants, unfortunately, the shelf-life of the study drug expired which resulted in early closure of the study after only 31 participants.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Seema Khan
Organization: Northwestern University
Phone: 312-503-4236
EMail: s-khan2@northwestern.edu
Layout table for additonal information
Responsible Party: Seema Khan, Northwestern University
ClinicalTrials.gov Identifier: NCT00952731     History of Changes
Other Study ID Numbers: NWU07-9-02
NCI-2013-00452 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
NCI 07-9-02 ( Other Identifier: Northwestern University )
NCI-2013-00452 ( Registry Identifier: Clinical Trials Reporting Program of NCI )
P30CA060553 ( U.S. NIH Grant/Contract )
N01CN35157 ( U.S. NIH Grant/Contract )
First Submitted: August 4, 2009
First Posted: August 6, 2009
Results First Submitted: May 27, 2015
Results First Posted: July 21, 2015
Last Update Posted: July 21, 2015