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| Name | Class |
|---|---|
| George Mason University | OTHER |
| University of Pittsburgh Medical Center | OTHER |
| United States Department of Defense | FED |
| U.S. Army Medical Research and Development Command |
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The purpose of this study is to test the hypothesis that chloroquine will reduce the ability of ductal carcinoma in situ (DCIS) to survive and spread. Participants will receive either chloroquine standard dose (500mg/week) or chloroquine low dose (250mg/week) for 1 month prior to surgical removal of the tumor.
The purpose of this study is to test the hypothesis that inhibiting the autophagy pathway in DCIS will reduce the capacity of DCIS to survive and invade. The study will examine the safety and effectiveness of neoadjuvant chloroquine administration for a one month period to patients with low, intermediate grade, or high grade DCIS. We will evaluate whether this treatment will reduce the capacity of DCIS neoplastic cells, existing within the duct, to survive, induce lesion regression, and kill the invasive DCIS progenitor cells.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Chloroquine Standard Dose (500mg/week) | Experimental | Patients with ER+ or ER- DCIS regardless of histologic grade will be randomly assigned to receive one month standard dose chloroquine (500 mg/week). |
|
| Chloroquine Low Dose (250mg/week) | Experimental | Patients with ER+ or ER- DCIS regardless of histologic grade will be randomly assigned to receive one month low dose chloroquine (250mg/week). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Chloroquine Standard Dose (500mg/week) | Drug | Patients will receive chloroquine (500 mg/once a week) for 1 month prior to surgical removal of the DCIS lesion. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Average Change in the Longest Diameter of the Breast MRI Target Lesion | One of the primary outcomes of this study was to measure the impact of weekly chloroquine on the amount of DCIS seen on MRI.The tumor response was evaluated by RECIST criteria. 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 The longest diameter of the target lesion or primary area of non-mass enhancement was measured by digital calipers. For one patient, the longest diameter was difficult to measure due to the presence of a significant post biopsy resolving hematoma at the biopsy site. Further correlation was made based on the extent of the pre-treatment microcalcifications and post treatment areas of non-mass enhancement. | Immediately preceding study drug treatment and again after treatment prior to surgery. The total time interval was up to 8 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Total Number of Treatment-Related Adverse Events | One of the outcomes was to ensure the safety of weekly chloroquine. Patients were followed clinically during the treatment with chloroquine and during their surgery and postoperative period ( including radiation therapy). Patients were verbally assessed for additional symptoms or concerns. Patients were also examined by the provider during treatment and follow up visits to the surgeon. |
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Inclusion Criteria:
If a subject is of child-bearing potential (women are considered not of child-bearing potential if they are at least one year postmenopausal and/or surgically sterile), she must have a documented negative serum or urine pregnancy test before starting treatment.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Kirsten H Edmiston, MD, FACS | Inova Fairfax Hospital Cancer Center | Principal Investigator |
| Priscilla McAuliffe, MD, PhD | Magee-Women's Hospital of UPMC | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Medical Oncology and Hematology Associates of Northern Virginia | Fairfax | Virginia | 22031 | United States | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20562526 | Derived | Martinez-Outschoorn UE, Pavlides S, Whitaker-Menezes D, Daumer KM, Milliman JN, Chiavarina B, Migneco G, Witkiewicz AK, Martinez-Cantarin MP, Flomenberg N, Howell A, Pestell RG, Lisanti MP, Sotgia F. Tumor cells induce the cancer associated fibroblast phenotype via caveolin-1 degradation: implications for breast cancer and DCIS therapy with autophagy inhibitors. Cell Cycle. 2010 Jun 15;9(12):2423-33. doi: 10.4161/cc.9.12.12048. Epub 2010 Jun 15. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Chloroquine Standard Dose (500mg/Week) | Patients with ER+ or ER- DCIS regardless of histologic grade will be randomly assigned to receive one month standard dose chloroquine (500 mg/week). Chloroquine Standard Dose (500mg/week): Patients will receive chloroquine (500 mg/once a week) for 1 month prior to surgical removal of the DCIS lesion. Breast Biopsy: Patients diagnosed with DCIS will undergo a breast biopsy prior to the start of study treatment. This biopsy is entirely voluntary and is not required to remain in the study. The biopsy will allow researchers to study the tissue for biomarkers and to determine how the DCIS tissue changes during treatment. Additional samples of the DCIS tissue will be collected at the time of surgery. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| FED |
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| Chloroquine Low Dose (250mg/week) | Drug | Patients will receive chloroquine (250 mg/once a week) for 1 month prior to surgical removal of the DCIS lesion. |
|
|
| Breast Biopsy | Procedure | Patients diagnosed with DCIS will undergo a breast biopsy prior to the start of study treatment. This biopsy is entirely voluntary and is not required to remain in the study. The biopsy will allow researchers to study the tissue for biomarkers and to determine how the DCIS tissue changes during treatment. Additional samples of the DCIS tissue will be collected at the time of surgery. |
|
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| The patients were monitored from the time of diagnosis through 6 months of surgical follow up. |
| Effect of Chloroquine on Proliferating Cell Nuclear Antigen (PCNA) Proliferation Index | We evaluated the effect of therapy on cellular proliferation as measured by the change in proliferating cell nuclear antigen (PCNA) proliferation index. PCNA , which is elevated during the G1/S phase of the cell cycle, may be used as a marker of cellular proliferation. The PCNA proliferation index was measured as the number of PCNA positive stained cells in the DCIS lesion/ total number of cells in the lesion. The change in the PCNA index is equal to the mean PCNA proliferation index pre-treatment minus the mean PCNA proliferation index post-treatment. | At the time of breast biopsy and again at time of surgery. |
| Impact of Chloroquine Treatment on the Cell Signaling Kinase Levels in DCIS Lesions. | The study evaluated the effect of chloroquine treatment on the proteomic signaling profiles of the DCIS lesions. Post treatment surgical specimens were evaluated by immunohistochemical staining to measure cell signaling kinase levels for CD68 and HMGB1. CD68 (Cluster Determinant 68) is a marker of macrophages/monocytes in the breast ducts. and HMGB1 (High Mobility Group Box 1) is involved in oxidative stress-mediated autophagy. HMGB1 is a non-histone DNA binding protein. The number of positive cells were quantified and recorded. . | At the time of surgery |
| Virginia Cancer Specialists, PC |
| Fairfax |
| Virginia |
| 22031 |
| United States |
| Virginia Surgery Associates | Fairfax | Virginia | 22033 | United States |
| Inova Fairfax Hospital | Falls Church | Virginia | 22042 | United States |
| FG001 | Chloroquine Low Dose (250mg/Week) | Patients with ER+ or ER- DCIS regardless of histologic grade will be randomly assigned to receive one month low dose chloroquine (250mg/week). Chloroquine Low Dose (250mg/week): Patients will receive chloroquine (250 mg/once a week) for 1 month prior to surgical removal of the DCIS lesion. Breast Biopsy: Patients diagnosed with DCIS will undergo a breast biopsy prior to the start of study treatment. This biopsy is entirely voluntary and is not required to remain in the study. The biopsy will allow researchers to study the tissue for biomarkers and to determine how the DCIS tissue changes during treatment. Additional samples of the DCIS tissue will be collected at the time of surgery. |
| COMPLETED |
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| NOT COMPLETED |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Chloroquine Standard Dose (500mg/Week) | Patients with ER+ or ER- DCIS regardless of histologic grade will be randomly assigned to receive one month standard dose chloroquine (500 mg/week). Chloroquine Standard Dose (500mg/week): Patients will receive chloroquine (500 mg/once a week) for 1 month prior to surgical removal of the DCIS lesion. Breast Biopsy: Patients diagnosed with DCIS will undergo a breast biopsy prior to the start of study treatment. This biopsy is entirely voluntary and is not required to remain in the study. The biopsy will allow researchers to study the tissue for biomarkers and to determine how the DCIS tissue changes during treatment. Additional samples of the DCIS tissue will be collected at the time of surgery. |
| BG001 | Chloroquine Low Dose (250mg/Week) | Patients with ER+ or ER- DCIS regardless of histologic grade will be randomly assigned to receive one month low dose chloroquine (250mg/week). Chloroquine Low Dose (250mg/week): Patients will receive chloroquine (250 mg/once a week) for 1 month prior to surgical removal of the DCIS lesion. Breast Biopsy: Patients diagnosed with DCIS will undergo a breast biopsy prior to the start of study treatment. This biopsy is entirely voluntary and is not required to remain in the study. The biopsy will allow researchers to study the tissue for biomarkers and to determine how the DCIS tissue changes during treatment. Additional samples of the DCIS tissue will be collected at the time of surgery. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||||
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Average Change in the Longest Diameter of the Breast MRI Target Lesion | One of the primary outcomes of this study was to measure the impact of weekly chloroquine on the amount of DCIS seen on MRI.The tumor response was evaluated by RECIST criteria. 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 The longest diameter of the target lesion or primary area of non-mass enhancement was measured by digital calipers. For one patient, the longest diameter was difficult to measure due to the presence of a significant post biopsy resolving hematoma at the biopsy site. Further correlation was made based on the extent of the pre-treatment microcalcifications and post treatment areas of non-mass enhancement. | The analysis population was the number of patients who underwent breast MRI both before and after treatment with chloroquine. (11/12 patients). The population was then further reduced to 10/12 due to the patient with a significant post biopsy hematoma. The extent of the pre-treatment DCIS could not be directly compared due to the presence of a significant hematoma. | Posted | Mean | Standard Deviation | percentage length change | Immediately preceding study drug treatment and again after treatment prior to surgery. The total time interval was up to 8 weeks |
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| ||||||||||||||||||||||||||||
| Secondary | Total Number of Treatment-Related Adverse Events | One of the outcomes was to ensure the safety of weekly chloroquine. Patients were followed clinically during the treatment with chloroquine and during their surgery and postoperative period ( including radiation therapy). Patients were verbally assessed for additional symptoms or concerns. Patients were also examined by the provider during treatment and follow up visits to the surgeon. | Patients who were treated | Posted | Number | Adverse Events (mortality, SAE, AE) | The patients were monitored from the time of diagnosis through 6 months of surgical follow up. |
| |||||||||||||||||||||||||||||||
| Secondary | Effect of Chloroquine on Proliferating Cell Nuclear Antigen (PCNA) Proliferation Index | We evaluated the effect of therapy on cellular proliferation as measured by the change in proliferating cell nuclear antigen (PCNA) proliferation index. PCNA , which is elevated during the G1/S phase of the cell cycle, may be used as a marker of cellular proliferation. The PCNA proliferation index was measured as the number of PCNA positive stained cells in the DCIS lesion/ total number of cells in the lesion. The change in the PCNA index is equal to the mean PCNA proliferation index pre-treatment minus the mean PCNA proliferation index post-treatment. | The groups were divided by chloroquine dose. Data was only available for 6 out of 12 patients. | Posted | Mean | Standard Error | Change in PCNA proliferation index | At the time of breast biopsy and again at time of surgery. |
| ||||||||||||||||||||||||||||||
| Secondary | Impact of Chloroquine Treatment on the Cell Signaling Kinase Levels in DCIS Lesions. | The study evaluated the effect of chloroquine treatment on the proteomic signaling profiles of the DCIS lesions. Post treatment surgical specimens were evaluated by immunohistochemical staining to measure cell signaling kinase levels for CD68 and HMGB1. CD68 (Cluster Determinant 68) is a marker of macrophages/monocytes in the breast ducts. and HMGB1 (High Mobility Group Box 1) is involved in oxidative stress-mediated autophagy. HMGB1 is a non-histone DNA binding protein. The number of positive cells were quantified and recorded. . | The analysis was performed stratifying chloroquine dose. | Posted | Mean | Standard Deviation | Positive cells | At the time of surgery |
|
The adverse event data was collected from the time that the chloroquin was initiated until 6 months after surgery.
The definitions of adverse events was consistent with the clinicaltrials.gov definitions.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Chloroquine Standard Dose (500mg/Week) | Patients with ER+ or ER- DCIS regardless of histologic grade will be randomly assigned to receive one month standard dose chloroquine (500 mg/week). Chloroquine Standard Dose (500mg/week): Patients will receive chloroquine (500 mg/once a week) for 1 month prior to surgical removal of the DCIS lesion. Breast Biopsy: Patients diagnosed with DCIS will undergo a breast biopsy prior to the start of study treatment. This biopsy is entirely voluntary and is not required to remain in the study. The biopsy will allow researchers to study the tissue for biomarkers and to determine how the DCIS tissue changes during treatment. Additional samples of the DCIS tissue will be collected at the time of surgery. | 0 | 7 | 0 | 7 | 0 | 7 |
| EG001 | Chloroquine Low Dose (250mg/Week) | Patients with ER+ or ER- DCIS regardless of histologic grade will be randomly assigned to receive one month low dose chloroquine (250mg/week). Chloroquine Low Dose (250mg/week): Patients will receive chloroquine (250 mg/once a week) for 1 month prior to surgical removal of the DCIS lesion. Breast Biopsy: Patients diagnosed with DCIS will undergo a breast biopsy prior to the start of study treatment. This biopsy is entirely voluntary and is not required to remain in the study. The biopsy will allow researchers to study the tissue for biomarkers and to determine how the DCIS tissue changes during treatment. Additional samples of the DCIS tissue will be collected at the time of surgery. | 0 | 5 | 0 | 5 | 0 | 5 |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Kirsten Edmiston, MD | Inova Health Care | 703-850-9555 | Kirsten.edmiston@inova.org |
| ID | Term |
|---|---|
| D002285 | Carcinoma, Intraductal, Noninfiltrating |
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D000071960 | Breast Carcinoma In Situ |
| D002278 | Carcinoma in Situ |
| D018299 | Neoplasms, Ductal, Lobular, and Medullary |
| D009371 | Neoplasms by Site |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| ID | Term |
|---|---|
| D002738 | Chloroquine |
| D001706 | Biopsy |
| ID | Term |
|---|---|
| D000634 | Aminoquinolines |
| D011804 | Quinolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D003581 | Cytodiagnosis |
| D003584 | Cytological Techniques |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D013048 | Specimen Handling |
| D003949 | Diagnostic Techniques, Surgical |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |
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| >=65 years |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
|
|
| OG001 |
| Chloroquine Low Dose (250mg/Week) |
Patients with ER+ or ER- DCIS regardless of histologic grade will be randomly assigned to receive one month low dose chloroquine (250mg/week). Chloroquine Low Dose (250mg/week): Patients will receive chloroquine (250 mg/once a week) for 1 month prior to surgical removal of the DCIS lesion. Breast Biopsy: Patients diagnosed with DCIS will undergo a breast biopsy prior to the start of study treatment. This biopsy is entirely voluntary and is not required to remain in the study. The biopsy will allow researchers to study the tissue for biomarkers and to determine how the DCIS tissue changes during treatment. Additional samples of the DCIS tissue will be collected at the time of surgery. |
|
|
Patients with ER+ or ER- DCIS regardless of histologic grade will be randomly assigned to receive one month low dose chloroquine (250mg/week). Chloroquine Low Dose (250mg/week): Patients will receive chloroquine (250 mg/once a week) for 1 month prior to surgical removal of the DCIS lesion. Breast Biopsy: Patients diagnosed with DCIS will undergo a breast biopsy prior to the start of study treatment. This biopsy is entirely voluntary and is not required to remain in the study. The biopsy will allow researchers to study the tissue for biomarkers and to determine how the DCIS tissue changes during treatment. Additional samples of the DCIS tissue will be collected at the time of surgery. |
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