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

• Sponsor: University of California, Davis (Other)
• Overall Status: Completed
• CT.gov ID: NCT01110174
• Collaborator: (none)
• Enrollment: 8
• Location: 1
• Arm: 1
• Duration (Months): 72
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Diagnostic Test: HD PET/CT	N/A

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 Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Assessing Response to Neoadjuvant Chemotherapy With Dedicated Breast High Definition PET/CT, Serum Glycomic Markers and Tissue Muc-1 Isoforms
• Study Start Date: Mar 1, 2010
• Actual Primary Completion Date: Mar 1, 2016
• Actual Study Completion Date: Mar 1, 2016

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Assess the Ability of the HD PET/CT to Predict Final Histopathologic NAC Response. [After the first cycle of Neoadjuvant chemotherapy (NAC)]

   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.

Secondary Outcome Measures

1. Correlate Serum Circulating BCa-related Glycan Profiles With Radiographic and Histopathologic Assessments of NAC Response. [Baseline, during and after chemotherapy]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, Davis Medical Center	Sacramento	California	United States	95817

Sponsors and Collaborators

• University of California, Davis

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of California, Davis
• ClinicalTrials.gov Identifier: NCT01110174
• Other Study ID Numbers: 216529; CCSO 010
• First Posted: Apr 26, 2010
• Last Update Posted: Nov 21, 2019
• Last Verified: Nov 1, 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes

Study Results

Participant Flow

Arm/Group Title	HD PET/CT
Arm/Group Description	utilization of PET/CT for diagnostic of breast cancer progression. HD PET/CT: imaging
Period Title: Overall Study
STARTED	8
COMPLETED	8
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	HD PET/CT
Arm/Group Description	utilization of PET/CT for diagnostic of breast cancer progression. HD PET/CT: imaging
Overall Participants	8
Age (Count of Participants)
<=18 years	NA NaN
Between 18 and 65 years	NA NaN
>=65 years	NA NaN
Sex: Female, Male (Count of Participants)
Female	NA NaN
Male	NA NaN
Region of Enrollment (participants) [Number]
United States	NA NaN

Outcome Measures

1. Primary Outcome

Title	Assess the Ability of the HD PET/CT to Predict Final Histopathologic NAC Response.
Description	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.
Time Frame	After the first cycle of Neoadjuvant chemotherapy (NAC)

Outcome Measure Data

Analysis Population Description

PI has left the institution, all efforts to locate PI and obtain this information have been exhausted and there is no access to this data

Arm/Group Title	HD PET/CT
Arm/Group Description	utilization of PET/CT for diagnostic of breast cancer progression. HD PET/CT: imaging
Measure Participants	0

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

PI has left institution, all efforts to locate secondary outcome measure data have been exhausted and there is no longer access to this data.

Arm/Group Title	HD PET/CT
Arm/Group Description	utilization of PET/CT for diagnostic of breast cancer progression. HD PET/CT: imaging
Measure Participants	0

Adverse Events

Arm/Group Title	HD PET/CT
Arm/Group Description	utilization of PET/CT for diagnostic of breast cancer progression. HD PET/CT: imaging
All Cause Mortality
	HD PET/CT
	Affected / at Risk (%)	# Events
Total	0/8 (0%)
Serious Adverse Events
	HD PET/CT
	Affected / at Risk (%)	# Events
Total	0/8 (0%)
Other (Not Including Serious) Adverse Events
	HD PET/CT
	Affected / at Risk (%)	# Events
Total	0/8 (0%)

Limitations/Caveats

Dr. Martinez, left UC Davis in 2013 and Dr. Bold was listed as PI. No new participants were enrolled under Dr. Bold, and he does not have access to the data. UC Davis does not have any means of contacting Dr. Martinez pursuant to results entry.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.