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3'-Deoxy-3'-18F Fluorothymidine PET/CT in Predicting Response To Chemotherapy Before Surgery in Patients With Locally Advanced Breast Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00572728
First received: December 11, 2007
Last updated: December 10, 2014
Last verified: August 2014

December 11, 2007
December 10, 2014
December 2008
September 2014   (final data collection date for primary outcome measure)
Change in FLT uptake between the baseline (pre-therapy) and the early-therapy imaging studies using pathological complete response as a gold standard [ Time Frame: Baseline (FLT-1) to early therapy (5-10 days after of chemotherapy, FLT-2) ] [ Designated as safety issue: No ]
Imaging parameters will be compared using receiver operating characteristic (ROC) curves. ROC will be estimated and the area under the curve, along with its 95% confidence interval, will be determined. The primary statistical evaluation will be based on the percent change in FLT SUV60 between baseline and early-treatment scans, using complete pathological response of the primary tumor as the confirmatory parameter.
18F]FLT uptake of the primary tumor in patients with locally advanced breast cancer [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00572728 on ClinicalTrials.gov Archive Site
  • Levels of tumor proliferation markers (Ki-67 and mitotic index) [ Time Frame: At time of surgery ] [ Designated as safety issue: No ]
    The [F-18] FLT imaging parameters will be evaluated for correlation with the immunohistochemical results: FLT-1 with the pre-therapy biopsy Ki-67 and mitotic index and, when there has not been a pCR and FLT-3 (and the change from baselines) with post-therapy surgical specimen Ki-67 and mitotic index. A Pearson correlation coefficient (or Spearman rank correlation if normality test fails) will be estimated and the 95% confidence interval will be determined using Fisher's Z transformation.
  • Pathological complete response [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
    A ROC curve will be estimated and the area under the curve, along with its 95% confidence interval, will be determined.
  • Residual cancer burden [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
    An ordinary linear regression will be used with the continuous measure RCB as response and the uptake parameters as covariates.
  • Clinical response [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
    A logistic regression approach will be used to evaluate the relationship between FLT-1, FLT-2 and FLT-3 uptake parameters and non-response of the primary tumor (stable or progressive disease) to therapy.
  • Regional metastasis to the lymph nodes [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
  • Change in FLT-2 and FLT-3 uptake parameters [ Time Frame: Early therapy (5-10 days after of chemotherapy, FLT-2) to post therapy (within 3 weeks prior to surgery) ] [ Designated as safety issue: No ]
    An ordinary linear regression will be used to compare change in FLT-2 and FLT-3 uptake parameters to changes in tumor size from other serial imaging modalities such as mammograms, MRI, and ultrasounds, as available.
  • Metabolic changes from FLT-1 [ Time Frame: Baseline (FLT-1) to post therapy (within 3 weeks prior to surgery, FLT-3) ] [ Designated as safety issue: No ]
    An ordinary linear regression will be used for this aim, with the metabolic changes from [18F] FDG- PET as response and the changes of [F-18] FLT uptake parameters as predictors. However, if the metabolic response from [F-18] FDG-PET can be dichotomized, a logistic regression will be used instead.
  • Incidence of adverse events and physiologic effects associated with 18F-FLT administration [ Time Frame: Up to 24 hours following each administration of 18F-FLT ] [ Designated as safety issue: Yes ]
Vital signs, clinical laboratory tests, ECG [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
3'-Deoxy-3'-18F Fluorothymidine PET/CT in Predicting Response To Chemotherapy Before Surgery in Patients With Locally Advanced Breast Cancer
Phase II Study of Fluorine-18 3'-Deoxy-3'-Fluorothymidine (F-18-FLT) in Invasive Breast Cancer

This phase II trial studies how well 3'-deoxy-3'-18F fluorothymidine (18F-FLT) positron emission tomography (PET)/computed tomography (CT) works in predicting response in patients receiving chemotherapy and undergoing surgery for breast cancer that has spread from where it started to nearby tissue or lymph nodes. Diagnostic procedures, such as 18F-FLT PET/CT, may help in learning how well chemotherapy works to kill breast cancer cells before surgery and help doctors plan the best treatment.

PRIMARY OBJECTIVES:

I. To correlate the percentage change in standardized uptake value at 60 minutes (SUV60) between baseline (FLT-1) and early-therapy (FLT-2) with pathologic complete response to neoadjuvant chemotherapy of the primary tumor in patients with locally advanced breast cancer.

SECONDARY OBJECTIVES:

I. To demonstrate correlation between FLT-1 and post-therapy (FLT-3) uptake parameters and tumor proliferation markers in locally advanced breast cancer.

II. To evaluate the relationship between FLT-1, FLT-2 and FLT-3 uptake parameters and pathologic complete response of the primary tumor and residual cancer burden (RCB).

III. To evaluate the relationship between FLT-1, FLT-2 and FLT-3 uptake parameters and non-response of the primary tumor (stable or progressive disease) to therapy.

IV. To evaluate the relationship between FLT-1, FLT-2 and FLT-3 uptake parameters and pathologic complete response to neoadjuvant chemotherapy in patients with regional disease in the lymph nodes in patients with locally advanced breast cancer.

V. To compare the changes of FLT-2 and FLT-3 uptake parameters to changes in tumor sizes from other serial imaging modalities such as mammograms, magnetic resonance imaging (MRI), and ultrasound.

VI. To compare the changes of FLT-2 and FLT-3 uptake parameters to metabolic changes from [18F] fludeoxyglucose (FDG)-PET, as available.

VII. To continue to monitor for potential safety issues and define any physiologic effects associated with 18F FLT administration.

OUTLINE:

Patients undergo 18F-FLT PET/CT at baseline (prior to chemotherapy, FLT-1), early therapy (5-10 days after the initiation of the first course of chemotherapy, FLT-2), and post therapy (within 3 weeks prior to surgery, FLT-3). Patients undergo standard surgical resection of residual tumor following completion of neoadjuvant chemotherapy.

Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
  • Stage IIB Breast Cancer
  • Stage IIIA Breast Cancer
  • Stage IIIB Breast Cancer
  • Stage IIIC Breast Cancer
  • Drug: Fluorothymidine F-18
    Undergo 18F-FLT PET/CT
    Other Names:
    • 18F-FLT
    • 3'-deoxy-3'-[18F]fluorothymidine
  • Procedure: Positron Emission Tomography
    Undergo 18F-FLT PET/CT
    Other Names:
    • Medical Imaging, Positron Emission Tomography
    • PET
    • PET Scan
    • Positron Emission Tomography
    • Positron Emission Tomography Scan
  • Procedure: Computed Tomography
    Undergo 18F-FLT PET/CT
    Other Names:
    • CAT
    • CAT Scan
    • Computed Tomography
    • CT
  • Other: Laboratory Biomarker Analysis
    Correlative studies
Experimental: Diagnostic (18F-FLT)
Patients undergo 18F-FLT PET/CT at baseline (prior to chemotherapy, FLT-1), early therapy (5-10 days after the initiation of the first course of chemotherapy, FLT-2), and post therapy (within 3 weeks prior to surgery, FLT-3). Patients undergo standard surgical resection of residual tumor following completion of neoadjuvant chemotherapy.
Interventions:
  • Drug: Fluorothymidine F-18
  • Procedure: Positron Emission Tomography
  • Procedure: Computed Tomography
  • Other: Laboratory Biomarker Analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
90
October 2014
September 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Pathologically confirmed breast cancer, determined to be a candidate for primary systemic (neoadjuvant) therapy and for surgical resection of residual primary tumor following completion of neoadjuvant therapy
  • Locally advanced breast cancer, not stage IV, and with a tumor size >= 2cm (as measured on imaging or estimated by physical exam)
  • No obvious contraindications for primary chemotherapy
  • Residual tumor planned to be removed surgically following completion of neoadjuvant therapy
  • Able to lie still for 1.5 hours for PET scanning
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
  • Leukocytes >= 3,000/ul
  • Absolute neutrophil count >= 1,500/ul
  • Platelets >= 100,000/ul
  • Total bilirubin within normal institutional limits
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 times the institutional upper limit of normal
  • Creatinine within normal institutional limits OR creatinine clearance >= 30 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • If female, postmenopausal for a minimum of one year, OR surgically sterile, OR not pregnant, confirmed by institutional standard of care (SOC) pregnancy test, and willing to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study participation
  • Able to understand and willing to sign a written informed consent document and a Health Insurance Portability and Accountability Act (HIPAA) authorization in accordance with institutional guidelines

Exclusion Criteria:

  • Previous treatment (chemotherapy, radiation, or surgery) to involved breast; including hormone therapy
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Medically unstable
  • Condition requiring anesthesia for PET scanning and/or unable to lie still for 1.5 hours
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to F-18 fluorothymidine
  • Pregnant or nursing
  • Previous malignancy, other than basal cell or squamous cell carcinoma of the skin or in situ carcinoma of the cervix, from which the patient has been disease free for less than 5 years
  • Currently on hormone therapy as the primary systemic neoadjuvant therapy
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00572728
NCI-2009-00266, NCI-2009-00266, HM11081, CDR0000689109, ACRIN 6688, 8029, N01CM27165
Yes
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Lale Kostakoglu American College of Radiology Imaging Network
National Cancer Institute (NCI)
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP