Pegylated Liposomal Doxorubicin Hydrochloride and Carboplatin Followed by Surgery and Paclitaxel in Treating Patients With Triple Negative Stage II-III Breast Cancer

NCT02315196 | Active Not Recruiting Phase 2 Results

• 4 other identifiers: 041401NCI-2014-02029Pro20140000477041401P30CA072720
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well pegylated liposomal doxorubicin hydrochloride and carboplatin followed by surgery and paclitaxel work in treating patients with stage II-III breast cancer that does not have estrogen receptors, progesterone receptors, or large amounts of human epidermal growth factor receptor 2 (HER2)/neu protein (triple negative). Drugs used in chemotherapy, such as pegylated liposomal doxorubicin hydrochloride, carboplatin, and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving pegylated liposomal doxorubicin hydrochloride and carboplatin before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving pegylated liposomal doxorubicin hydrochloride and carboplatin followed by surgery and paclitaxel may be an effective treatment for breast cancer.

Conditions

Estrogen Receptor-negative Breast Cancer; HER2-negative Breast Cancer; Progesterone Receptor-negative Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Triple-negative Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Rate of Pathologic Complete Response (pCR) Based on Response Evaluation Criteria in Solid Tumors Criteria

  The pCR rate will first be determined as proportions and calculating its 95% confidence interval. To study the association between pCR response (yes/no) and the presence of gross residual disease, type and number of mutations, clinical lymph node status (positive/negative), tumor size (\< 2 cm/\>= 2 cm) based on p53, logistic regression analysis will be used, controlling for cancer treatment and disease stage and other covariates if numbers allow.

  Disease was evaluated at baseline to after four cycles every 28 days and then after twelve weeks of treatment after surgery (up to 28 weeks from baseline).

Secondary Outcomes (2)

• OS

  Time from initiation of chemotherapy until death from any cause, assessed up to 20 years

• Mutational Spectrum of Tumors

  Time from initiation of chemotherapy until death from any cause, assessed up to 20 yearsUp to 20 years

Study Arms (1)

Treatment (doxil, carboplatin, surgery, paclitaxel)

EXPERIMENTAL

NEOADJUVANT: Patients receive pegylated liposomal doxorubicin hydrochloride\* IV over 90 minutes and carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. ADJUVANT: Patients undergo definitive surgery at the discretion of the treating physician. Patients then receive paclitaxel IV over 60 minutes once weekly for 12 weeks in the absence of disease progression or unacceptable toxicity. \*NOTE: If there is a shortage of pegylated liposomal doxorubicin hydrochloride, patients receive epirubicin hydrochloride IV over 15-20 minutes on day 1.

Drug: pegylated liposomal doxorubicin hydrochloride; Drug: epirubicin hydrochloride; Drug: carboplatin; Procedure: therapeutic conventional surgery; Drug: paclitaxel; Other: laboratory biomarker analysis; Other: quality-of-life assessment

Interventions

pegylated liposomal doxorubicin hydrochloride DRUG

Given IV

Also known as: CAELYX, Dox-SL, DOXIL, doxorubicin hydrochloride liposome, LipoDox

Treatment (doxil, carboplatin, surgery, paclitaxel)

epirubicin hydrochloride DRUG

Given IV

Also known as: 4'-epi-doxorubicin HCl, 4'-epiadriamycin

Treatment (doxil, carboplatin, surgery, paclitaxel)

carboplatin DRUG

Given IV

Also known as: Carboplat, CBDCA, JM-8, Paraplat, Paraplatin

Treatment (doxil, carboplatin, surgery, paclitaxel)

therapeutic conventional surgery PROCEDURE

Undergo definitive surgery

Treatment (doxil, carboplatin, surgery, paclitaxel)

paclitaxel DRUG

Given IV

Also known as: Anzatax, Asotax, TAX, Taxol

Treatment (doxil, carboplatin, surgery, paclitaxel)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (doxil, carboplatin, surgery, paclitaxel)

quality-of-life assessment OTHER

Ancillary studies

Also known as: quality of life assessment

Treatment (doxil, carboplatin, surgery, paclitaxel)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women with previously untreated, unilateral stage II-III breast cancer, ER/PgR/HER2 negative (ER =\< 5%, PgR =\< 5%, HER2 0-1+ by immunohistochemistry \[IHC\] or fluorescence in situ hybridization \[FISH\] =\< 2.0); if clinically negative lymph nodes, tumor size should be minimum 1.0 cm and identifiable under office-based ultrasound guidance
• Negative serum or urine beta-human chorionic gonadotropin (hCG) pregnancy test at screening for patients of child-bearing potential within one week prior to enrollment
• Patients with reproductive potential must use an adequate contraceptive method (e.g. abstinence, intrauterine device, oral contraceptives, barrier device with spermicide or surgical sterilization) during treatment and for three months after completing treatment
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status \< 2
• Life expectancy \>= 52 weeks excluding their diagnosis of breast cancer
• Absolute neutrophil count (ANC) \>= 1,500 cells/mm\^3
• Platelets \>= 100,000 cells/mm\^3
• Hemoglobin \> 9.0 g/dL
• Creatinine \< 2.5 mg/dL
• Total bilirubin \< 1.5 X upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) \< 2.5 X institutional ULN
• Patients must have normal cardiac function, as evidenced by a left ventricular ejection fraction (LVEF) within institutional normal limits; echocardiogram may be used if multi gated acquisition (MUGA) scan is not available, but the same test must be used throughout the study to evaluate LVEF
• Computed tomography of the chest, abdomen, and pelvis (CT CAP) and bone scan performed within 30 days prior to study entry and does not demonstrate metastatic disease
• Patients may not receive concurrent treatment with other investigational or commercial agent(s) for treatment of their breast cancer
• The patient or, if applicable, her legally authorized representative must have signed and dated an Institutional Review Board (IRB)-approved consent form that conforms to federal and institutional guidelines

You may not qualify if:

• Women who are pregnant or breastfeeding
• Second primary malignancy except most situ carcinoma (e.g. in situ carcinoma of the cervix, adequately treated non-melanomatous carcinoma of the skin) or other malignancy treated at least 5 years previously with no evidence of recurrence
• Definitive clinical or radiologic evidence of metastatic disease; imaging must have been performed no greater than 30 days prior to initiation of chemotherapy
• Diagnosis of inflammatory breast cancer
• History of hypersensitivity reactions attributed to a conventional formulation of doxorubicin hydrochloride (HCL) or the components of doxil, paclitaxel, or carboplatin
• Serious concomitant systemic disorders (including active infections or chronic infection requiring suppressive antibiotics) that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator
• Myocardial infarct or unstable angina within 6 months before enrollment, New York Heart Association (NYHA) class II or greater heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, clinically significant pericardial disease, valvular disease with documented compromise in cardiac function, or electrocardiographic evidence of acute ischemic or active conduction system abnormalities
• Prior anthracycline, platinum salt, or taxane for any malignancy
• Known or active hepatitis B or C with abnormal liver function tests
• Significant vascular disease (e.g., aortic aneurysm, aortic dissection)
• Symptomatic peripheral vascular disease
• Evidence of bleeding diathesis or coagulopathy
• Intrinsic lung disease resulting in moderate to severe dyspnea
• History of a major organ allograft or condition requiring chronic immunosuppression, e.g., kidney, liver, lung, heart, bone marrow transplant, or autoimmune diseases; this includes treatment with corticosteroids within one month (dose of \>= 10 mg/day methylprednisolone equivalent) (excluding inhaled steroids); patients who have received corneal transplants, cadaver skin, or bone transplants are eligible
• Nervous system disorder (paresthesias, peripheral motor neuropathy, or peripheral sensory neuropathy) \>= grade 2, per the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0)

Sponsors & Collaborators

• Rutgers, The State University of New Jersey: lead
• National Cancer Institute (NCI): collaborator
• Rutgers Cancer Institute of New Jersey: collaborator

Study Sites (1)

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

liposomal doxorubicin; Epirubicin; Carboplatin; Paclitaxel; Taxes

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Coordination Complexes; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations

Results Point of Contact

• Title: Deborah L Toppmeyer, MD
• Organization: Cancer Institute of New Jersey

toppmede@cinj.rutgers.edu

732-235-6789

Study Officials

• Kim Hirshfield

  Rutgers Cancer Institute of New Jersey

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: October 28, 2014
• First Posted: December 11, 2014
• Study Start: February 25, 2015
• Primary Completion: February 8, 2021
• Study Completion (Estimated): July 1, 2041
• Last Updated: March 29, 2023
• Results First Posted: March 29, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)