NCT00856492|CompletedPhase 2ResultsDMC

S0800, Nab-Paclitaxel, Doxorubicin, Cyclophosphamide, and Pegfilgrastim With or Without Bevacizumab in Treating Women With Inflammatory or Locally Advanced Breast Cancer

A Randomized Phase II Trial of Weekly Nanoparticle Albumin Bound Paclitaxel (Nab-Paclitaxel) (NSC-736631) With or Without Bevacizumab, Either Preceded by or Followed by Q 2 Week Doxorubicin (A)and Cyclophosphamide (C) Plus Pegfilgrastim (PEG-G) as Neoadjuvant Therapy For Inflammatory and Locally Advanced HER-2/NEU Negative Breast Cancer

SWOG Cancer Research Network ClinicalTrials.gov

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3 other identifiers

CDR0000636131S0800U10CA032102

Study Type

interventional

Target

215

Locations

2 countries

Sites

366

Timeline

RegisteredMar 2009

StartedApr 2010

CompletionDec 2015

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as paclitaxel albumin-stabilized nanoparticle formulation, doxorubicin, and cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Colony-stimulating factors, such as pegfilgrastim, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of chemotherapy. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some find tumor cells and kill them or carry tumor-killing substances to them. Others interfere with the ability of tumor cells to grow and spread. Bevacizumab may also may stop the growth of tumor cells by blocking blood flow to the tumor. Giving these treatments before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. It is not yet known which treatment regimen is more effective in treating women with breast cancer. PURPOSE: This randomized phase II trial is studying paclitaxel albumin-stabilized nanoparticle formulation, doxorubicin, cyclophosphamide, and pegfilgrastim to compare how well they work when given with or without bevacizumab in treating women with inflammatory or locally advanced breast cancer.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

215

participants targeted

Target at P75+ for phase_2 breast-cancer

Timeline

Completed

Started Apr 2010

Typical duration for phase_2 breast-cancer

Geographic Reach

2 countries

366 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

5.7 years study duration

First Submitted

Initial submission to the registry

March 4, 2009

Completed

1 day until next milestone

First Posted

Study publicly available on registry

March 5, 2009

Completed

1.1 years until next milestone

Study Start

First participant enrolled

April 1, 2010

Completed

5.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2015

Completed

2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2015

Completed

1.6 years until next milestone

Results Posted

Study results publicly available

June 27, 2017

Completed

Last Updated

June 27, 2017

Status Verified

May 1, 2017

Enrollment Period

5.5 years

First QC Date

March 4, 2009

Results QC Date

November 15, 2016

Last Update Submit

May 23, 2017

Conditions

Breast Cancer

Keywords

inflammatory breast cancerstage II breast cancerstage IIIA breast cancerstage IIIB breast cancerHER2-negative breast cancerestrogen receptor-negative breast cancerestrogen receptor-positive breast cancerprogesterone receptor-negative breast cancerprogesterone receptor-positive breast cancerstage IIIC breast cancer

Outcome Measures

Primary Outcomes (1)

Number of Patients With Pathological Complete Response Rate
Pathologic complete response (pCR), commonly defined as the absence of residual invasive cancer in both the breast and axillary lymph nodes, has emerged as a surrogate endpoint for disease-free and overall survival, as the achievement of a pCR is associated with a favorable long-term prognosis in all breast cancer subtypes.
pre-study pathology vs. post-chemo surgery pathology (approx. 39-42 weeks post-randomization)

Secondary Outcomes (3)

Overall Survival
Disease assessed every 4 weeks while on treatment then every 6 months for one year then annually for four years from registration.
Event-free Survival
Disease assessed every 4 weeks while on treatment then every 6 months for one year then annually for four years from registration or until recurrence
Number of Adverse Events That Are Possibly, Probably or Definitely Related to Study Drug
Up to 28 weeks

Study Arms (3)

Arm 1

EXPERIMENTAL

Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on day 1 and bevacizumab IV over 30- to 90-minutes on day 1 of weeks 1-12. Patients then receive doxorubicin hydrochloride IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2 of weeks 14, 16, 18, 20, 22, and 24.

Biological: bevacizumabBiological: pegfilgrastimDrug: cyclophosphamideDrug: doxorubicin hydrochlorideDrug: paclitaxel albumin-stabilized nanoparticle formulation

Arm 2

ACTIVE COMPARATOR

Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on day 1 of weeks 1-12, and then receive doxorubicin hydrochloride IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2 of weeks 14, 16, 18, 20, 22, and 24.

Biological: pegfilgrastimDrug: cyclophosphamideDrug: doxorubicin hydrochlorideDrug: paclitaxel albumin-stabilized nanoparticle formulation

Arm 3

ACTIVE COMPARATOR

Patients receive doxorubicin hydrochloride IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2 of weeks 1, 3, 5, 7, 9, and 11, and then receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on day 1 of weeks 14-25.

Biological: pegfilgrastimDrug: cyclophosphamideDrug: doxorubicin hydrochlorideDrug: paclitaxel albumin-stabilized nanoparticle formulation

Interventions

bevacizumabBIOLOGICAL

Given IV

Arm 1

pegfilgrastimBIOLOGICAL

Given subcutaneously

Arm 1Arm 2Arm 3

cyclophosphamideDRUG

Given IV

Arm 1Arm 2Arm 3

doxorubicin hydrochlorideDRUG

Given IV

Arm 1Arm 2Arm 3

paclitaxel albumin-stabilized nanoparticle formulationDRUG

Given IV

Arm 1Arm 2Arm 3

Eligibility Criteria

Age18 Years+

Sexfemale

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically or pathologically confirmed breast cancer meeting one of the following criteria: * Locally advanced disease (stage IIIB disease, stage IIB/IIIA, or stage IIIC disease) * Inflammatory disease meeting the following two clinicopathologic criteria: * Diffuse erythema AND edema (peau d'orange) of the breast involving the majority of the skin of the breast, i.e., more than 50% * A biopsy demonstrating cancer either within the dermal lymphatics OR in the breast parenchyma itself * HER2/neu-negative tumor as demonstrated by 0 or 1+ (weak or no staining) by DAKO, IHC, or equivalent test OR no gene amplification by FISH\* * 2+ by DAKO or IHC allowed provided FISH\* negative * NOTE: \*A negative FISH test ratio is \< 1.8 or FISH HER2 gene copy \< 4.0; if only a positive or negative result is available from the FISH test, a negative result is acceptable for study entry * Hormone receptor status known PATIENT CHARACTERISTICS: * Menopausal status not specified * Zubrod performance status 0-2 * Granulocyte count \> 1,500/mm\^3 * ANC ≥ 1,500/mm\^3 * Platelet count \> 100,000/mm\^3 * Hemoglobin 9.0 g/dL * Serum creatinine ≤ 1.5 times upper limit of normal (ULN) * Bilirubin ≤ 1.5 mg/dL * ALT and AST ≤ 3 times ULN * Alkaline phosphatase ≤ 2.5 ULN (unless bone metastasis is present in the absence of liver metastasis) * Urine protein:creatinine ratio ≤ 0.5 OR urine protein \< 1,000 mg on 24-hour urine collection * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * Able to take oral medications (e.g., no uncontrolled nausea, vomiting, or diarrhea, lack of physical integrity of the upper gastrointestinal tract, or malabsorption syndrome) * QTc \< 500 msec by EKG * LVEF normal by MUGA or ECHO (for patients with hypertension or for patients \> 60 years of age) * NYHA class II cardiac function by baseline ECHO/MUGA (for patients who have received central thoracic radiotherapy that included the heart in the radiotherapy port, or for patients who have a history of class II heart failure but are asymptomatic on treatment are eligible) * No history of stroke (cerebrovascular accident), transient ischemic attack, or cardiac event within the past 12 months, including any of the following: * Myocardial infarction (including severe/unstable angina) * Coronary/peripheral artery bypass graft * Symptomatic congestive heart failure * Pulmonary embolism * No poorly controlled hypertension, defined as recurrent or persistent (≥ 24 hours) elevated blood pressure (i.e., systolic blood pressure ≥ 140 mm Hg and/or diastolic blood pressure ≥ 90 mm Hg) * No other malignancy within the past 5 years except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer * Peripheral neuropathy \< grade 2 PRIOR CONCURRENT THERAPY: * No prior tyrosine kinase inhibitors * More than 5 years since prior chemotherapy, radiotherapy, or biologic therapy (e.g., trastuzumab or bevacizumab) for invasive breast cancer * At least 7 days since prior hormonal therapy * At least 7 days since prior and no concurrent strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole) or grapefruit juice * No concurrent CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, St. John's wort) * No other concurrent therapy for the treatment of breast cancer except for bisphosphonates * No concurrent brachytherapy

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

SWOG Cancer Research Networklead
National Cancer Institute (NCI)collaborator

Study Sites (366)

Providence Cancer Center at Providence Hospital

Mobile, Alabama, 36608, United States

Location

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Alta Bates Summit Comprehensive Cancer Center

Berkeley, California, 94704, United States

Location

Roy and Patricia Disney Family Cancer Center at Providence Saint Joseph Medical Center

Burbank, California, 91505, United States

Location

Peninsula Medical Center

Burlingame, California, 94010, United States

Location

East Bay Radiation Oncology Center

Castro Valley, California, 94546, United States

Location

Valley Medical Oncology Consultants - Castro Valley

Castro Valley, California, 94546, United States

Location

Valley Medical Oncology

Fremont, California, 94538, United States

Location

Loma Linda University Cancer Institute at Loma Linda University Medical Center

Loma Linda, California, 92354, United States

Location

Breastlink Medical Group, Incorporated at Long Beach Memorial Medical Center

Long Beach, California, 90806, United States

Location

Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

USC/Norris Comprehensive Cancer Center and Hospital

Los Angeles, California, 90089-9181, United States

Location

Contra Costa Regional Medical Center

Martinez, California, 94553-3156, United States

Location

Tibotec Therapeutics - Division of Ortho Biotech Products, LP

Marysville, California, 95901, United States

Location

El Camino Hospital Cancer Center

Mountain View, California, 94040, United States

Location

Sutter Health - Western Division Cancer Research Group

Novato, California, 94945, United States

Location

Highland General Hospital

Oakland, California, 94602, United States

Location

Alta Bates Summit Medical Center - Summit Campus