Carboplatin and Paclitaxel Albumin-Stabilized Nanoparticle Formulation Before Surgery in Treating Patients With Locally Advanced or Inflammatory Triple Negative Breast Cancer

Tracking Information
First Submitted Date ICMJE	January 27, 2012
First Posted Date ICMJE	February 3, 2012
Last Update Posted Date	May 8, 2018
Study Start Date ICMJE	February 15, 2012
Estimated Primary Completion Date	February 2019 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: February 1, 2012)	pCR or Symmans 0-1 pathological response [ Time Frame: At completion of definitive surgery ]; A two stage design using MD Anderson criteria of lack of evidence of any residual invasive tumor in breast and/or regional lymph node.
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01525966 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: December 5, 2012)	Overall survival [ Time Frame: 5 years from completion of study treatment ]Estimated by the Kaplan-Meier method. The corresponding median survival times (with 90% confidence limits) will be determined.; Progression-free survival [ Time Frame: 5 years from completion of study treatment ]Estimated by the Kaplan-Meier method. The corresponding median survival times (with 90% confidence limits) will be determined.; Number of patients experiencing serious adverse events (SAEs) graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: 30 days after completion of study treatment ]SAEs will be characterized by type of adverse event and grade, and by the time of onset in relation to the first day of therapy for each cycle. Attribution of SAEs to treatment (unrelated, unlikely, possible, probable, or definite) will also be reported. The cumulative percentage of patients experiencing treatment-related SAEs and its relationship to treatment duration will also be reported.
Original Secondary Outcome Measures ICMJE; (submitted: February 1, 2012)	Overall survival [ Time Frame: 5 years from completion of study treatment ]; Progression-free survival [ Time Frame: 5 years from completion of study treatment ]; Number of patients experiencing serious adverse events (SAEs) [ Time Frame: 30 days after completion of study treatment ]
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Carboplatin and Paclitaxel Albumin-Stabilized Nanoparticle Formulation Before Surgery in Treating Patients With Locally Advanced or Inflammatory Triple Negative Breast Cancer
Official Title ICMJE	Phase II Trial of Neoadjuvant Chemotherapy With Carboplatin and NAB-Paclitaxel in Patients With Locally Advanced and Inflammatory Triple Negative Breast Cancer
Brief Summary	This phase II trial studies how well giving carboplatin and paclitaxel albumin-stabilized nanoparticle formulation together before surgery works in treating patients with locally advanced or inflammatory triple negative breast cancer. Drugs used in chemotherapy, such as carboplatin and paclitaxel albumin-stabilized nanoparticle formulation, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.
Detailed Description	PRIMARY OBJECTIVES: I. To test the hypothesis that carboplatin + nab-paclitaxel (paclitaxel albumin-stabilized nanoparticle formulation) therapy will demonstrate a promising neoadjuvant pathologic complete response (pCR) rate for eligible patients. II. To test the hypothesis that carboplatin + nab-paclitaxel therapy will demonstrate a promising Symmans 0-1 pathological response rate for eligible patients. SECONDARY OBJECTIVES: I To evaluate the overall survival and event-free survival of eligible patients treated with carboplatin + nab-paclitaxel neoadjuvant chemotherapy. II. To evaluate the toxicities and tolerance of carboplatin + nab-paclitaxel therapy in this patient population. III. To evaluate the role of laboratory correlates in response, toxicity and survival endpoints. IV. To procure tissue and perform analysis of gene and protein expression profiles of pre-treatment primary tumor (estimated success rate: 80%) and residual tumors (25%) and lymph nodes including the study of tumor niche (50%), studying sequential assessment of cellular characteristics and gene and protein expression profiles. V. To identify specific mutations in tumor deoxyribonucleic acid (DNA) in comparison to adjacent tissue and germ line DNA procured prior to, during, and subsequent to neoadjuvant chemotherapy, and to detect/measure, as feasible, the presence of such mutations in fragmented circulating DNA from plasma, and to correlate these mutations with the presence/characteristics of circulating tumor cells in order to identify prognostic and predictive indicators of persisting/relapsed disease and targets for therapy. VI. To assess ribonucleic acid (RNA) (using Mammaprint/Blueprint and 44,000 Agilent platform gene array), (micro) miRNA and exosome and protein profiles in tumor, adjacent tissue and plasma prior to, during, and at completion of neoadjuvant chemotherapy in order to establish prognostic and predictive indicators of outcome, markers of persistent/relapsed disease, and targets for therapy. VII. To analyze tumor DNA and genomic DNA from plasma by microarray and reverse transcriptase (RT)-polymerase chain reaction (PCR) analysis to assess copy numbers/single nucleotide polymorphisms (SNP)/genomic polymorphisms in genes for the purposes of establishing prognostic and predictive indicators of outcomes; markers of persistence/relapse disease, drug resistance, and drug metabolism; and targets of therapy. VIII. To assess the prognostic and predictive value of conventional pathological features (stage, estrogen and progesterone receptor and human epidermal growth factor receptor [HER-2] status, presence of lymphovascular invasion, high grade tumor status) in comparison to such values derived from the molecular approaches. IX. To procure tumor from the primary and definitive surgical specimen for the purpose of establishing breast cancer stem cell lines. X. To procure blood samples for the purpose of identifying and characterizing circulating tumor cells. OUTLINE: Patients receive carboplatin intravenously (IV) over 30 minutes on day 1 and paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes once weekly. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 4 years and then every 6 months for 1 year and then periodically thereafter.
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Inflammatory Breast Cancer; Stage IIA Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Triple-negative Breast Cancer; Stage IIB Breast Cancer; Estrogen Receptor Negative; Progesterone Receptor Negative; HER2/Neu Negative
Intervention ICMJE	Drug: carboplatin Given IV Other Names: Carboplat CBDCA JM-8 Paraplat Paraplatin; Drug: paclitaxel albumin-stabilized nanoparticle formulation Given IV Other Names: ABI-007 nab paclitaxel nab-paclitaxel nanoparticle albumin-bound paclitaxel; Other: laboratory biomarker analysis Correlative studies
Study Arms	Experimental: Treatment (carboplatin and nab-paclitaxel); Patients receive carboplatin IV over 30 minutes on day 1 and paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes once weekly. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.; Interventions: Drug: carboplatin; Drug: paclitaxel albumin-stabilized nanoparticle formulation; Other: laboratory biomarker analysis
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Recruiting
Estimated Enrollment ICMJE; (submitted: January 7, 2016)	69
Original Estimated Enrollment ICMJE; (submitted: February 1, 2012)	45
Estimated Study Completion Date	February 2019
Estimated Primary Completion Date	February 2019 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Patients must be diagnosed with locally advanced (T2 and higher with or without lymph node involvement), and/or inflammatory triple negative breast cancer; Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately; Tumor negative for expression of hormone receptors (< 1%) and not over-expressing HER2 by immunohistochemistry (IHC) (0-1), or in case of IHC of 2, negative by fluorescence in situ hybridization (FISH) or by alternative gene testing; Bilirubin =< 1.5 mg/dL; Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2 x upper limit of normal; Alkaline phosphatase =< 2 x upper limit of normal; Platelets >= 100,000 cells/mm^3; Hemoglobin > 9.0 g/dL; Absolute neutrophil count (ANC) >= 1,500 cells/mm^3; Creatinine =< 1.5 mg/dL is recommended; however, institutional norms are acceptable; Left ventricular ejection fraction > 50%; Women of childbearing potential and sexually active males must use an effective contraception method during treatment and for three months after completing treatment; Negative serum or urine beta-human chorionic gonadotropin (hCG) pregnancy test screening for patients of childbearing potential; All subjects must have the ability to understand and the willingness to sign a written informed consent; No prior therapies are allowed for the treatment of the newly diagnosed breast cancer; patients with a prior diagnosis of malignancy treated >= 5 years ago are eligible, provided that they have not received prior taxanes or carboplatin as part of their prior treatment regimen, and that they meet all eligibility criteria Exclusion Criteria: Known active hepatitis B or C; Known active human immunodeficiency virus (HIV); Prior breast cancer or other invasive malignancy treated within 5 years; Pregnancy; Neuropathy > grade 1; Any other intercurrent medical/psychological problem deemed exclusionary by the treating physician or investigators/primary investigator (PI); Subjects will be excluded who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study
Sex/Gender	Sexes Eligible for Study: Female
Ages	19 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01525966
Other Study ID Numbers ICMJE	11174; NCI-2012-00025 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	City of Hope Medical Center
Study Sponsor ICMJE	City of Hope Medical Center
Collaborators ICMJE	National Cancer Institute (NCI)
Investigators ICMJE	Principal Investigator: Yuan Yuan, MD, PhD City of Hope Medical Center
PRS Account	City of Hope Medical Center
Verification Date	May 2018
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP