Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Carcinoma

Breast Neoplasms

Carcinoma, Ductal

Carcinoma in Situ

Carcinoma, Lobular

Breast Carcinoma In Situ

Carcinoma, Intraductal, Noninfiltrating

Carcinoma, Ductal, Breast

Breast Diseases

Skin Diseases

30 mastectomy, partial mastectomy, and mammoplasty samples will be analyzed to define the effective post-excision time window in which the device must be used before the results can no longer be evaluated. The mammoplasty specimens are necessary to assess normal tissue outcomes.

25 Partial Mastectomy cases will be analyzed to distinguish between different implementation methods of the technology.

Nimmi Ramanujam, PhD

The objective of the proposed research is to develop a clinical-trial-ready device and to evaluate its practical utility as a routinely used intra-operative tool. Our multidisciplinary group has previously shown that optical techniques can effectively discriminate between malignant and non-malignant breast tissues. The proposed technology will be a multi-channel optical assay device for intra-operative imaging of margins in specimens excised from patients undergoing breast conserving surgery (partial mastectomy) or mastectomy.

Fast Spectral Imaging Device for Tumor Margin Mapping

(1) In order to define the effective post-excision time window in which the device must be used, which ultimately has bearings on the final product indications for use. (2)To analyze the different methods of implementation of the technology.

National Institutes of Health (NIH)

National Cancer Institute (NCI)

Duke University

Antineoplastic Agents

All Drugs and Chemicals

Etanidazole

Single arm study analyzing tumor hypoxia after EF5 injection

An infusion of EF5, a fluorinated 2-nitroimidazole, will be administered using the recommended dose of 21mg/kg one day prior to surgical procedure.

A small tissue sample will be removed from the excised tissue and will be stored for later analysis.

Partial or Total Mastectomy

Mark W Dewhirst, DVM, PhD

The purpose of this pilot study is to determine the prevalence of markers of chronic and cycling hypoxia and reactive species stress (oxidative and nitrosative) in the breast cancer tumor microenvironment. The study is based around four cornerstone features of the pathologic microenvironment - Hypoxia, Reactive Species (reactive oxygen and nitrogen species), HIF-1 and VEGF, which we term the HRHV axis. Fifty breast cancer patients with planned surgical excision will be administered the hypoxia marker drug, EF5, 24-36 hr prior to surgical excision. EF5 is a non-therapeutic drug and provides no direct benefit to those patients enrolled in this pilot study. Tissues obtained intra-operatively will be snap frozen and subsequently analyzed for EF5 binding. Immunohistochemical analysis of a cohort of immunohistochemical and urine markers that depict the HRHV axis will be examined. The association of the markers with the presence of hypoxia, as determined by EF5 positivity, will be determined. Data from this pilot study will be used to establish the prevalence of markers of the HRHV axis in breast cancer. This information will be crucial for future human trials in which the HRHV axis is therapeutically targeted.

To Evaluate the Characteristics of a Breast Cancer

Pilot Study to Characterize the HRHV Axis in the Microenvironment of Breast Cancers

Mark Dewhirst

Professor

Bone Density Conservation Agents

Tamoxifen

Letrozole

Palbociclib

Aromatase Inhibitors

Enzyme Inhibitors

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Selective Estrogen Receptor Modulators

Estrogen Receptor Modulators

Protein Kinase Inhibitors

Tamoxifen is given in the Window of Treatment phase for 2 weeks followed by Endocrine Therapy for 24 weeks.

Letrozole is given in the Window of Treatment phase for 2 weeks followed by Endocrine Therapy for 24 weeks.

Tamoxifen is given in the Window of Treatment phase for 2 weeks followed by Endocrine Therapy in combination with Palbociclib for 24 weeks.

Letrozole is given in the Window of Treatment phase for 2 weeks followed by Endocrine Therapy in combination with Palbociclib for 24 weeks.

Endocrine Therapy

Otto Metzger, MD

This research study is evaluating how well Breast Cancer responds to preoperative treatment with Endocrine treatment in combination with a drug called Palbociclib or Endocrine treatment alone as possible treatments for Hormone Receptor Positive Breast Cancer.

This is an open label phase II neoadjuvant clinical trial of Palbociclib in combination with endocrine therapy for hormone receptor positive early-stage breast cancer. The planned sample size is 180 participants. The study includes a "window treatment" phase followed by a treatment phase. In the window phase, participants will be treated with a two-week course of tamoxifen (Arm A) or letrozole (Arm B). In the treatment phase participants will be randomized to receive endocrine therapy in combination with palbociclib (Arm C) or endocrine therapy alone (Arm D) for a total duration of 24 weeks. Premenopausal patients with either invasive lobular or ductal carcinoma will be eligible to enroll directly into the treatment phase of the study. The study has two co-primary objectives: 1) To evaluate the difference in anti-proliferative activity of letrozole versus tamoxifen measured by changes in Ki67 from baseline to research biopsy (day 15) within cohorts of hormone receptor positive breast cancer for patients with invasive lobular and ductal carcinoma. 2) To evaluate the pathologic complete response (pCR) of endocrine therapy plus palbociclib and of endocrine therapy alone in breast cancer patients diagnosed with hormone receptor positive invasive breast cancer.

Palbociclib and Endocrine Therapy for LObular Breast Cancer Preoperative Study (PELOPS)

Palbociclib and Endocrine Therapy for LObular Breast Cancer Preoperative Study (PELOPS): A Randomized Phase II Study of Palbociclib With Letrozole Versus Letrozole Alone for Invasive Lobular Carcinoma and Invasive Ductal Carcinoma

Log fold change in anti-proliferative activity of Letrozole versus Tamoxifen within cohorts of hormone receptor positive breast cancer for patients with invasive lobular and ductal carcinoma during the window phase. Higher absolute value indicates larger change in the anti-proliferative activity

Residual Cancer Burden index (RCB) between hormone receptor positive invasive breast cancer patients given endocrine therapy plus palbociclib (Arm C) and endocrine therapy alone (Arm D). RCB score is used to assess the response to neoadjuvant chemotherapy in breast cancer patients and is in a scale of 0 to infinity. Higher RCB score indicates more tumor burden remaining, thus worse outcome.

Odds Ratio of Achieving Cell Cycle Arrest at the end of Window Phase in hormone receptor positive invasive breast cancer patients given Tamoxifen vs Letrozole. Cell cycle arrest is defined to be percentage of Ki67\<2.7

The estimate of RCB index change for patients who receive both endocrine and Palbociclib instead of endocrine alone, but have the same lymph node status, tumor size and menopausal status. RCB score is used to assess the response to neoadjuvant chemotherapy in breast cancer patients and is in a scale of 0 to infinity. Higher RCB score indicates more tumor burden remaining, thus worse outcome.

RCB response is defined as RCB-0 or RCB-I; RCB not response is defined as RCB-II or RCB-III Residual Cancer Burden (RCB) considers residual disease in the tumor bed and lymph nodes after NAC, generating a continuous score which is then grouped into four categories: RCB-0, RCB-I, RCB-II and RCB-III. Higher RCB group reflects more tumor burden remaining, thus worse outcome

Percentage of Participants with Clinical Response in Arm C and Arm D in Breast cancer patients diagnosed with hormone receptor positive invasive breast cancer; Clinical response rate is defined as the number of partial and complete responses after preoperative endocrine therapy plus palbociclib (Arm C) and of endocrine therapy alone (Arm D)

Pfizer

Dana-Farber Cancer Institute

Serious AEs are defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. AEs were collected without specifying which phase they occurred in and are reported by patients' treatment sequence, which is consistent with the participant flow and considered as the most feasible way.

Tamoxifen is given in the window phase for 2 weeks; Endocrine therapy in combination with Palbociclib are given in the treatment phase for 24 weeks

Arm A Tamoxifen First, Then Arm C Endocrine With Palbociclib

Tamoxifen is given in the window phase for 2 weeks; Endocrine therapy alone is given in the treatment phase for 24 weeks

Arm A Tamoxifen First, Then Arm D Endocrine Alone

Letrozole is given in the window phase for 2 weeks; Endocrine therapy in combination with Palbociclib are given in the treatment phase for 24 weeks

Arm B Letrozole First, Then Arm C Endocrine With Palbociclib

Letrozole is given in the window phase for 2 weeks; Endocrine therapy alone is given in the treatment phase for 24 weeks

Arm B Letrozole First, Then Arm D Endocrine Alone

Tamoxifen is given in the window phase for 2 weeks

Arm A Tamoxifen Only

Letrozole is given in the window phase for 2 weeks

Arm B Letrozole Only

Endocrine therapy in combination with Palbociclib are given in the treatment phase for 24 weeks

Arm C Endocrine With Palbociclib Only

Endocrine therapy alone is given in the treatment phase for 24 weeks

Arm D Endocrine Alone Only

Tamoxifen is given in the window phase for 2 weeks; Endocrine therapy in combination with Palbociclib are given in the treatment phase for 24 weeks.

Tamoxifen is given in the window phase for 2 weeks; Endocrine therapy alone is given in the treatment phase for 24 weeks.

Letrozole is given in the window phase for 2 weeks; Endocrine therapy in combination with Palbociclib are given in the treatment phase for 24 weeks.

Letrozole is given in the window phase for 2 weeks; Endocrine therapy alone is given in the treatment phase for 24 weeks.

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race

Menopausal Status

Baseline Histology

This is based on the diagnostic test and shows the extent the tumor spread to the lymph nodes. Higher stage is associated with worse outcome.

Baseline clinical N stage

This is based on the diagnostic test and describes the size and location of the tumor. Higher stage is associated with worse outcome.

Baseline clinical T stage

This stage was assigned by combining the tumor size/location, node, metastasis, tumor grade, and the results of ER/PR and HER2 testing results. Higher stage is associated with worse outcome.

Baseline Invasive Primary Breast Cancer Stage

Surgery Type

Otto Metzger

Patients with invasive ductal/both histology receiving Tamoxifen in the window phase

Tamoxifen With Invasive Ductal

Patients with invasive ductal/both histology receiving Letrozole in the window phase

Letrozole With Invasive Ductal

Patients with invasive lobular histology receiving Tamoxifen in the window phase

Tamoxifen With Invasive Lobular

Patients with invasive lobular histology receiving Letrozole in the window phase

Letrozole With Invasive Lobular

Patients both not missing baseline and day15 Ki67 were included into the analysis population

Difference in Anti-proliferative Activity of Patients Given Letrozole Versus Tamoxifen During the Window Phase

Endocrine therapy in combination with Palbociclib are given in the treatment phase for 24 weeks.

Arm C Endocrine With Palbociclib

Arm D Endocrine Therapy Alone

Patients with treatment and surgery are included into the analysis population

Pathologic Complete Response (pCR) of Patients Given Endocrine Therapy Plus Palbociclib and of Endocrine Therapy Alone During the Treatment Phase

Patients with invasive ductal/both histology receiving Tamoxifen vs Letrozole in the window phase

Tamoxifen vs Letrozole in Invasive Ductal Patients

Patients with invasive lobular histology receiving Tamoxifen vs Letrozole in the window phase

Tamoxifen vs Letrozole in Invasive Lobular Patients

Odds Ratio of Achieving Cell Cycle Arrest at the End of Window Phase

Endocrine therapy in combination with Palbociclib

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Fast Spectral Imaging Device for Tumor Margin Mapping	NCT01107080	Breast Cancer		18 Years -	Duke University
Fast Spectral Imaging Device for Tumor Margin Mapping	NCT01107080	Breast Cancer		18 Years -	Duke University
To Evaluate the Characteristics of a Breast Cancer	NCT01055678	Breast Cancer	EF5 Partial or Tota...	18 Years -	Duke University
Palbociclib and Endocrine Therapy for LObular Breast Cancer Preoperative Study (PELOPS)	NCT02764541	Breast Cancer	Letrozole Tamoxifen Palbociclib Endocrine Thera...	18 Years -	Dana-Farber Cancer Institute

Spots Global Cancer Trial Database for invasive lobular carcinoma