Study Of Intraductal Carboplatin In Women With Ductal Carcinoma In Situ (DCIS)

Study Overview
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Brief Summary
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The primary objective of this study is to compare the safety of 100 mg carboplatin administered intraductally once on Day 1 or twice on Days 1 and 15 in women with ductal carcinoma in situ (DCIS) undergoing surgical management 2 to 4 weeks following the Day 15 intraductal infusion. Secondary objectives are to characterize the biologic and clinical effects with respect to: pharmacokinetics, extent of disease on MRI and mammogram, histopathological assessment of DCIS, and biomarker measurement of Ki-67, TUNEL and G-actin.

Detailed Description
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This is a randomized, 3-arm, saline-controlled study involving women undergoing surgical management of DCIS. Forty-five (45) women who have been diagnosed with DCIS by core biopsy will receive intraductal administration of either carboplatin or normal saline (NS) into the DCIS-involved breast duct. Thirty (30) patients (i.e., 15 patients per arm) will receive two intraductal infusions of either 100 mg of carboplatin or NS on Days 1 and 15. Fifteen (15) patients will receive an intraductal infusion of 100 mg carboplatin on Day 1 and an intraductal infusion of NS on Day 15. Patients will undergo surgical resection 2 to 4 weeks following the Day 15 intraductal infusion (i.e. 4 to 6 weeks from diagnosis). The effect of carboplatin on DCIS in the pre-treatment core biopsy specimen and the resection specimen will be assessed. Venous blood samples will be collected for carboplatin PK analysis pre-dose and at 30 minutes, 1, 2, 4, and 8 hours following intraductal infusions on Days 1 and 15.

Official Title
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A Phase II Randomized Study Of Intraductal Carboplatin In Women With Ductal Carcinoma In Situ

Conditions
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Ductal Carcinoma In Situ

Intervention / Treatment
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* Drug: Carboplatin i.d. Days 1 & 15
* Drug: Carboplatin i.d. Day 1; Normal Saline i.d. Day 15
* Drug: Normal Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female 18 years of age or older Scheduled to undergo surgical resection in 2 weeks or longer Pathological diagnosis of DCIS requiring surgical resection DCIS diagnosed with core biopsy Mammogram within 6 weeks of diagnosis Adequate organ function as defined by the following criteria: Absolute neutrophil count (ANC) ≥ 1500/μl, Platelets ≥ 140,000/μl,Hemoglobin ≥ 12.0 g/dl, Creatinine < 2.0 mg/dl - Able to sign informed consent Exclusion Criteria: Current diagnosis of invasive or inflammatory breast carcinoma DCIS with microinvasion on histology on core needle biopsy Palpable mass Mass on mammography Concurrent anti-cancer therapy Prior exposure to carboplatin (related to current or past diagnosis) Prior radiation to the breast or chest wall Prior areolar or breast surgery which interrupts communication of the ductal systems with the nipple Presence of breast implants Presence of ulcerating or fungal skin lesions or infection of the breasts Pregnant or lactating Impaired cardiac function or history of cardiac problems Poor nutritional state (as determined by clinician) Presence of serious infection Scheduled for intraoperative radiation of breast or chest wall Allergies to lidocaine or marcaine Allergies to imaging dyes

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>Carboplatin infused into DCIS-involved duct on Days 1 & 15 | Drug: Carboplatin i.d. Days 1 & 15<br>* Carboplatin, 10 mg/ml, 10 ml (100 mg) infused into DCIS-involved duct on Days 1 & 15<br>* Other names: Paraplatin;|
| Experimental: B<br>Carboplatin infused into DCIS-involved duct Day 1 and Normal Saline infused into DCIS-involved duct on Day 15 | Drug: Carboplatin i.d. Day 1; Normal Saline i.d. Day 15<br>* Carboplatin 10 mg/ml, 10 ml (100 mg) i.d. DCIS duct on Day 1 Normal Saline, 10 ml i.d. DCIS duct on Day 15<br>* Other names: Paraplatin;|
| Placebo Comparator: C<br>Normal Saline infused into DCIS-involved duct Days 1 & 15 | Drug: Normal Saline<br>* Normal Saline, 10 ml, i.d. on Days 1 and 15<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare the safety of 100 mg carboplatin administered intraductally once on Day 1 or twice on Days 1 and 15 in women with ductal carcinoma in situ (DCIS) undergoing surgical management 2 to 4 weeks following the Day 15 intraductal infusion |  | 2 to 4 weeks following the Day 15 intraductal infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| characterize i.d. carboplatin pharmacokinetics |  | 4 -8 weeks | 
| characterize clinical extent of disease on MRI and/or mammogram |  | 2 - 4 weeks | 
| characterize the histopathological assessment of DCIS |  | 4 - 10 weeks | 
| Biomarker measurement of Ki-67, TUNEL and G-actin |  | 4 - 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ductal Carcinoma In Situ, DCIS, Breast Cancer, Carboplatin, Intraductal