Assessing Response to Neoadjuvant Chemotherapy With HD PET/CT, Serum Glycomic Markers and Tissue Muc-1 Isoforms (ENIGMA)

Assessing Response to Neoadjuvant Chemotherapy With Dedicated Breast High Definition PET/CT, Serum Glycomic Markers and Tissue Muc-1 Isoforms

A pilot study of adult (≥ 18 years) women with stage II-III breast cancer who will receive preoperative chemotherapy prior to mastectomy. Patients will have real-time serum glycan profiling, expression of tissue MUC 1 oncoprotein isoforms to predict neoadjuvant chemotherapy response and additional mammography and HD PET/CT examinations to assess response. The investigators hypothesize that a functional tumor assessment utilizing high-definition positron emission tomography/computed tomography (HD PET/CT), real-time serum glycan profiling, and expression of tissue MUC 1 oncoprotein isoforms will predict neoadjuvant chemotherapy response in breast cancer patients.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Diagnostic test: HD PET/CT

Detailed Description

This is a non-randomized clinical trial pilot study. Consenting adult (≥ 18 years) women with stage II-III breast cancer undergoing will receive neoadjuvant chemotherapy with a standard ACT regimen prior to mastectomy. Prior to beginning chemotherapy, patients will receive a baseline mammogram, breast HD PET/CT, and blood draw. Not more than 7 days prior to the second cycle of chemotherapy, patients will have both HD PET/CT and diagnostic mammography images taken to assess early response to treatment. Patients will have two additional mammography and HD PET/CT examinations: one after the first cycle of chemotherapy, and another upon completion of the last cycle of chemotherapy but before mastectomy. The investigators will collect data on the size (maximum diameter, estimated volume) and 18FDG uptake (SUV) of the known primary breast cancer on HD PET/CT. Blood will be sampled from patients at 12 separate time points during the study for glycan analysis. At least 3 ml will be taken with each blood draw. The first blood draw will be taken when the patient agrees to enroll in the study. The second blood draw will be taken prior to the first cycle of chemotherapy. Thereafter, blood will be drawn for serum glycan analysis after each cycle of chemotherapy is completed. After the patient undergoes mastectomy, tissue will be collected for MUC-1 assay and two additional blood draws will be taken.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Sacramento, California, United States, 95817
      • University of California, Davis Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Patient must sign informed consent to participate in the study.
• Patient must be ≥ 18 years of age.
• Histologic diagnosis of invasive breast cancer(ductal or lobular)
• Stage II or III breast cancer and considered a candidate for curative mastectomy.
• Selected mastectomy for surgical option of treatment.
• Patient must agree to receive standard or dose-dense adriamycin, cyclophosphamide, and taxane-based chemotherapy given preoperatively.
• Patient must have the following preoperative laboratory values confirmed within 28 days prior to registration: Creatinine ≤ 1.5 times ULN. Platelets ≥ 90,000/mm3. White blood count ≥ 1,500/mm3. PT/PTT ≤ the institution ULN. Patients of child-bearing potential must have a negative urine or serum pregnancy test.
• If a patient is a cancer survivor, the patient must have undergone potentially curative therapy for all prior malignancies, with no evidence of prior malignancy for at least 5 years (except for effectively treated basal cell or squamous cell carcinoma of the skin, or carcinoma-in-situ of the cervix treated by surgery alone).
• The primary breast tumor must be detectable by mammogram at the time of diagnosis
• Estimated cardiac ejection fraction ≥ 50% by echocardiogram or MUGA
• ECOG performance status 0-1.

Exclusion Criteria:

• Non-invasive breast cancer, benign breast disease, or tumor histology other than stage II or stage III invasive ductal carcinoma, invasive lobular carcinoma, or mixed ductal and lobular carcinoma.
• The patient has known distant metastatic disease.
• The patient wishes to pursue breast conservation.
• The patient is male.
• The patient is receiving preoperative chemotherapy other than adriamycin, cyclophosphamide, and a taxane (ACT) in standard or dose-dense fashion.
• The patient is pregnant or breast feeding.
• The primary tumor is not visualized by mammogram at the time of diagnosis.
• The patient's estimated cardiac ejection fraction is <50% by echocardiogram or MUGA.
• The patient has a documented intravenous contrast allergy or iodine allergy.
• Her-2/neu positive patients by IHC or FISH who receive trastuzumab neoadjuvantly; patients who are Her-2/neu positive but elect not to receive trastuzumab neoadjuvantly are still eligible for participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HD PET/CT; utilization of PET/CT for diagnostic of breast cancer progression.	Diagnostic test: HD PET/CT; imaging

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess the Ability of the HD PET/CT to Predict Final Histopathologic NAC Response.	Patients will have a HD PET/CT at baseline and another after the first cycle of NAC and upon completion.The goal is to distinguish NAC responders from non-responders and to accurately identify the size and extent of residual disease.	After the first cycle of Neoadjuvant chemotherapy (NAC)

Secondary Outcome Measures

Outcome Measure	Time Frame
Correlate Serum Circulating BCa-related Glycan Profiles With Radiographic and Histopathologic Assessments of NAC Response.	Baseline, during and after chemotherapy

Collaborators and Investigators

• Sponsor: University of California, Davis
• Investigators: Principal Investigator: Steve Martinez, MD, University of California, Davis

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: April 22, 2010
• First Submitted That Met QC Criteria: April 23, 2010
• First Posted (Estimate): April 26, 2010

Study Record Updates

• Last Update Posted (Actual): November 21, 2019
• Last Update Submitted That Met QC Criteria: November 13, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Other Study ID Numbers: 216529; CCSO 010

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes