Neoplasms, BreastPhase 2NCT00849472
Treatment With Pazopanib for Neoadjuvant Breast Cancer
A Phase 2 study testing doxorubicin + cyclophosphamide, paclitaxel + pazopanib and surgery in people with Neoplasms, Breast, run by GlaxoSmithKline at 143 sites in 2 countries.
Trial summary
The purpose of this study is to determine whether the treatment of a doxorubicin in combination with cyclophosphamide followed by a combination of pazopanib in combination with paclitaxel prior to surgery results in a pathological complete response in females with breast cancer. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Neoplasms, Breast
- What is being tested?
- doxorubicin + cyclophosphamide, paclitaxel + pazopanib and surgery
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 101 participants
- Where
- 143 sitesin 2 countries
- Study dates
- Jul 2009to Apr 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The patient must have consented to participate and must have signed and dated an appropriate IRB-approved consent form that conforms to federal and institutional guidelines for the study treatment and submission of tumor and blood samples required for the FB-6 correlative science studies
- The ECOG performance status must be 0 or 1
- Patients must have the ability to swallow oral medication.
- The diagnosis of invasive adenocarcinoma of the breast must have been made by core needle biopsy or limited incisional biopsy.
- Patients must have ER analysis performed on the primary tumor prior to randomization. If ER analysis is negative, then PgR analysis must also be performed. (Patients are eligible with either hormone receptor-positive or hormone receptor-negative tumors.)
- Patients must have clinical stage IIIA, IIIB, or IIIC disease with a mass in the breast or axilla measuring at least 2.0 cm by physical exam, unless the patient has inflammatory breast cancer, in which case measurable disease by physical exam is not required.
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- Adequate organ function
- LVEF assessment by 2-D echocardiogram or MUGA scan performed within 3 months prior to study entry must be greater or equal to 50% regardless of the facility's LLN.
- ECG performed within 4 weeks before study entry must demonstrate a QTc interval that is less than or equal to 0.47 seconds.
- The TSH level must be within normal limits for the laboratory.
Who cannot join
- Tumor that has been determined to be HER2-positive by immunohistochemistry (3+) or by FISH or CISH (positive for gene amplification), or has been determined to be HER2-equivocal and the investigator plans to administer trastuzumab or other targeted therapy.
- FNA alone to diagnose the primary breast cancer.
- Excisional biopsy or lumpectomy performed prior to study entry.
- Surgical axillary staging procedure prior to study entry.
- Definitive clinical or radiologic evidence of metastatic disease.
- History of ipsilateral invasive breast cancer regardless of treatment or ipsilateral DCIS treated with RT.
Show all 36Show fewer
- Contralateral invasive breast cancer at any time.
- Non-breast malignancies unless the patient is considered to be disease-free for 5 or more years prior to study entry and is deemed by her physician to be at low risk for recurrence. Patients with the following cancers are eligible if diagnosed and treated within the past 5 years: carcinoma in situ of the cervix, carcinoma in situ of the colon, melanoma in situ, and basal cell and squamous cell carcinoma of the skin.
- Requirement for chronic use of any of the prohibited medications or substances
- Previous therapy with anthracyclines, taxanes, or pazopanib for any malignancy.
- Treatment including RT, chemotherapy, and/or targeted therapy, administered for the currently diagnosed breast cancer prior to study entry.
- Continued therapy with any hormonal agent such as raloxifene, tamoxifen, or other SERM.
- Any sex hormonal therapy, e.g., birth control pills and ovarian hormone replacement therapy
- History of hepatitis B or C.
- Symptomatic pancreatitis or asymptomatic greater or equal to grade 2 elevation of amylase or lipase as per NCI CTCAE v3.0.
- History of documented pancreatitis.
- Uncontrolled hypertension defined as systolic BP greater than 140 mmHg or diastolic BP greater greater than 90 mmHg, with or without anti-hypertensive medication.
- History of hypertensive crisis or hypertensive encephalopathy.
- Cardiac disease that would preclude the use of any of the drugs included in the FB-6 treatment regimen.
- History of TIA or CVA.
- History of any arterial thrombotic event within 12 months prior to study entry.
- Pulmonary embolism or DVT within 6 months prior to study entry.
- Symptomatic peripheral vascular disease.
- Any significant bleeding within 6 months prior to study entry, exclusive of menorrhagia in premenopausal women.
- Known bleeding diathesis, coagulopathy, or requirement for therapeutic doses of coumadin.
- Serious or non-healing wound, skin ulcers, or bone fracture.
- Gastroduodenal ulcer(s) determined by endoscopy to be active.
- History of GI perforation, abdominal fistulae, or intra-abdominal abscess.
- Malabsorption syndrome, ulcerative colitis, inflammatory bowel disease, resection of the stomach or small bowel, or other disease significantly affecting gastrointestinal function.
- Sensory/motor neuropathy greater or equal to grade 2, as defined by the NCI's CTCAE v3.0.
- Conditions that would prohibit intermittent administration of corticosteroids for paclitaxel premedication.
- Anticipation of need for major surgical procedures (other than the required breast surgery) during the course of study therapy and for at least 3 months following the last dose of pazopanib.
- Pregnancy or lactation at the time of study entry.
- Other nonmalignant systemic disease that would preclude the patient from receiving study treatment or would prevent required follow-up.
- Known immediate or delayed hypersensitivity reaction to doxorubicin, cyclophosphamide, paclitaxel, pazopanib, or drugs chemically related to pazopanib.
- Use of any investigational agent within 4 weeks prior to enrollment in the study.
Trial locations and contacts
143 sites in 2 countries.
143 sites in 2 countries
United States137 sites
GSK Investigational Site
Ann Arbor, Michigan, 48106
GSK Investigational Site
Antioch, California, 94531
GSK Investigational Site
Baltimore, Maryland, 21237
GSK Investigational Site
Battle Creek, Michigan, 49016
GSK Investigational Site
Brighton, Michigan, 48114
GSK Investigational Site
Brunsville, Minnesota, 55337
GSK Investigational Site
Byron Center, Michigan, 49519
GSK Investigational Site
Canton, Ohio, 44710
GSK Investigational Site
Chargrin, Ohio, 44122
GSK Investigational Site
Charlotte, North Carolina, 28203
GSK Investigational Site
Charlotte, North Carolina, 28204
GSK Investigational Site
Charlotte, North Carolina, 28210
GSK Investigational Site
Charlotte, North Carolina, 28211
GSK Investigational Site
Charlotte, North Carolina, 28262
GSK Investigational Site
Chippewa Falls, Wisconsin, 54729
GSK Investigational Site
Clevand, Ohio, 44106
GSK Investigational Site
Clinton, North Carolina, 28328
GSK Investigational Site
Colorado Springs, Colorado, 80907
GSK Investigational Site
Dayton, Ohio, 45331
GSK Investigational Site
Dayton, Ohio, 45415
GSK Investigational Site
Dayton, Ohio, 45429
GSK Investigational Site
Dearborn, Michigan, 48123
GSK Investigational Site
Dearborn, Michigan, 48162
GSK Investigational Site
Decatur, Alabama, 35601
GSK Investigational Site
Denver, Colorado, 80205
GSK Investigational Site
Denver, Colorado, 80210
GSK Investigational Site
Denver, Colorado, 80218
GSK Investigational Site
Denver, Colorado, 80224
GSK Investigational Site
Denver, Colorado, 80244
GSK Investigational Site
Detroit, Michigan, 48236
GSK Investigational Site
Eau Claire, Wisconsin, 54701
GSK Investigational Site
Edina, Minnesota, 55435
GSK Investigational Site
Englewood, Colorado, 80113
GSK Investigational Site
Ephrata, Pennsylvania, 17522
GSK Investigational Site
Fernandina Beach, Florida, 32034
GSK Investigational Site
Flint, Michigan, 48502
GSK Investigational Site
Flint, Michigan, 48503
GSK Investigational Site
Flint, Michigan, 48532
GSK Investigational Site
Fremont, California, 94538
GSK Investigational Site
Fridley, Minnesota, 55432
GSK Investigational Site
Gainesville, Florida, 32610
GSK Investigational Site
Goldsboro, North Carolina, 27534
GSK Investigational Site
Grand Rapids, Michigan, 49503
GSK Investigational Site
Greeley, Colorado, 80631
GSK Investigational Site
Greensburg, Pennsylvania, 15601
GSK Investigational Site
Greenville, North Carolina, 27834
GSK Investigational Site
Grosse Point Woods, Michigan, 19229
GSK Investigational Site
Hayward, California, 94545
GSK Investigational Site
Honolulu, Hawaii, 96819
GSK Investigational Site
Huntsville, Alabama, 35801
GSK Investigational Site
Huntsville, Alabama, 35805
GSK Investigational Site
Iowa City, Iowa, 52242
GSK Investigational Site
Jacksonville, Florida, 32205
GSK Investigational Site
Jacksonville, Florida, 32207
GSK Investigational Site
Jacksonville, Florida, 32256
GSK Investigational Site
Jacksonville, Florida, 32258
GSK Investigational Site
Jeffersonville, Kentucky, 47130
GSK Investigational Site
Kettering, Ohio, 45409
GSK Investigational Site
Kettering, Ohio, 45429
GSK Investigational Site
Lafayette, Colorado, 80026
GSK Investigational Site
Lansing, Michigan, 48910
GSK Investigational Site
Lansing, Michigan, 48912
GSK Investigational Site
Lebanon, Ohio, 45036
GSK Investigational Site
Livonia, Michigan, 48154
GSK Investigational Site
Louisville, Kentucky, 40202
GSK Investigational Site
Louisville, Kentucky, 40207
GSK Investigational Site
Louisville, Kentucky, 40217
GSK Investigational Site
Louisville, Kentucky
GSK Investigational Site
Lubbock, Texas, 79410
GSK Investigational Site
Maplewood, Minnesota, 55109
GSK Investigational Site
Marshfield, Wisconsin, 54449
GSK Investigational Site
Mentor, Ohio, 44060
GSK Investigational Site
Middletown, Ohio, 45042
GSK Investigational Site
Minneapolis, Minnesota, 55433
GSK Investigational Site
Minneapolis, Minnesota, 55454
GSK Investigational Site
Minocqua, Wisconsin, 54548
GSK Investigational Site
Mount Clemens, Michigan, 48043
GSK Investigational Site
Muskegon, Michigan, 49444
GSK Investigational Site
New Brunswick, New Jersey, 08901
GSK Investigational Site
Oakland, California, 94611
GSK Investigational Site
Orange Park, Florida, 32073
GSK Investigational Site
Philadelphia, Pennsylvania, 19107
GSK Investigational Site
Philadelphia, Pennsylvania, 19115
GSK Investigational Site
Philadelphia, Pennsylvania, 19141
GSK Investigational Site
Pittsburgh, Pennsylvania, 15212
GSK Investigational Site
Pittsburgh, Pennsylvania, 15213
GSK Investigational Site
Pittsburgh, Pennsylvania, 15215
GSK Investigational Site
Pittsburgh, Pennsylvania, 15232
GSK Investigational Site
Pittsburgh, Pennsylvania, 15237
GSK Investigational Site
Port Huron, Michigan, 48060
GSK Investigational Site
Portland, Oregon, 97213
GSK Investigational Site
Portland, Oregon, 97225
GSK Investigational Site
Portland, Oregon
GSK Investigational Site
Redwood City, California, 94063
GSK Investigational Site
Rhinelander, Wisconsin, 54501
GSK Investigational Site
Rice Lake, Wisconsin, 54868
GSK Investigational Site
Richmond, California, 94801
GSK Investigational Site
Richmond, Virginia, 23235
GSK Investigational Site
Richmond, Virginia, 23298
GSK Investigational Site
Roseville, California, 95661
GSK Investigational Site
Sacramento, California, 95823
GSK Investigational Site
Sacramento, California, 95825
GSK Investigational Site
Saginaw, Michigan, 48601
GSK Investigational Site
Saint Louis Park, Minnesota, 55416
GSK Investigational Site
Saint Paul, Minnesota, 55101
GSK Investigational Site
Saint Paul, Minnesota, 55102
GSK Investigational Site
San Francisco, California, 94115
GSK Investigational Site
San Jose, California, 95119-1110
GSK Investigational Site
San Rafael, California, 94903
GSK Investigational Site
Santa Clara, California, 95051
GSK Investigational Site
Santa Rosa, California, 95403-2192
GSK Investigational Site
Savannah, Georgia, 31404
GSK Investigational Site
Savannah, Georgia, 31405
GSK Investigational Site
Seattle, Washington, 98101
GSK Investigational Site
South San Francisco, California, 94080
GSK Investigational Site
Stevens Point, Wisconsin, 54481
GSK Investigational Site
Stockton, California, 95210
GSK Investigational Site
Stony Brook, New York, 11794
GSK Investigational Site
Traverse City, Michigan, 49684
GSK Investigational Site
Vacaville, California, 95688
GSK Investigational Site
Vallejo, California, 94589
GSK Investigational Site
Vancouver, Washington, 98668
GSK Investigational Site
Vancover, Washington, 98684
GSK Investigational Site
Walnut Creek, California, 94596
GSK Investigational Site
Warren, Michigan, 48093
GSK Investigational Site
West Reading, Pennsylvania, 19611
GSK Investigational Site
Westlake, Ohio, 44145
GSK Investigational Site
Weston, Wisconsin, 54476
GSK Investigational Site
Wheat Ridge, Colorado, 80033
GSK Investigational Site
Wheat Ridge, Colorado, 80333
GSK Investigational Site
Wilminton, Ohio, 45042
GSK Investigational Site
Wilson, North Carolina, 27893
GSK Investigational Site
Winston-Salem, North Carolina, 27014
GSK Investigational Site
Winston-Salem, North Carolina, 27157
GSK Investigational Site
Wisconsin Rapids, Wisconsin, 54494
GSK Investigational Site
Woodbury, Minnesota, 55125
GSK Investigational Site
Xenia, Ohio, 45385
Canada6 sites
GSK Investigational Site
Montreal, Quebec, H2L 4M1
GSK Investigational Site
Montreal, Quebec, H3A 1A1
GSK Investigational Site
Montreal, Quebec, H3G 1A4
GSK Investigational Site
Montreal, Quebec, H3T 1E2
GSK Investigational Site
Ottawa, Ontario, K1H 8L6
GSK Investigational Site
Québec, Quebec, G1S 4L8
About this study
Official title: A Phase II Clinical Trial of Four Cycles of Doxorubicin and Cyclophosphamide Followed by Weekly Paclitaxel Given Concurrently With Pazopanib as Neoadjuvant Therapy Followed by Postoperative Pazopanib for Women With Locally Advanced Breast Cancer
The purpose of this study is to determine whether the treatment of a doxorubicin in combination with cyclophosphamide followed by a combination of pazopanib in combination with paclitaxel prior to surgery results in a pathological complete response in females with breast cancer.
Read the detailed description
This is a phase II non-randomized, multi-center study aimed to evaluate the efficacy and safety of the combination of pazopanib and paclitaxel following treatment with cyclophosphamide and doxorubicin for the treatment of neoadjuvant breast cancer.
Patients will receive standard doses of AC every 21 days for 4 cycles. This will be followed by weekly paclitaxel 80 mg/m2 IV on Days 1, 8, and 15 every 28 days for 4 cycles given concurrently with pazopanib 800 mg PO daily starting with the first paclitaxel dose and continuing until 7 days before surgery. Clinical complete response rate will be determined by tumor assessments performed by palpation at two time points: following AC (before paclitaxel/pazopanib begins) and 2-4 weeks following the last dose of paclitaxel (before surgery). Following recovery from preoperative therapy, patients will undergo the clinically-indicated surgery. Pazopanib will resume 4-6 weeks after surgery and continue daily for 6 months of postoperative pazopanib therapy.
- Conditions
- Neoplasms, Breast
- Being tested
- doxorubicin + cyclophosphamide, paclitaxel + pazopanib, surgery, pazopanib monotherapy
- Keywords
- Neoadjuvant Breast Cancer, Pazopanib (GW786034), NSABP Foundation, Inc., cyclophosphamide, Paclitaxel, Doxorubicin
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
doxorubicin + cyclophosphamideDrug
4 cycles of doxorubicin + cyclophosphamide followed by 4 cycles of paclitaxel + pazopanib.
paclitaxel + pazopanibDrug
4 cycles of paclitaxel + pazopanib
surgeryProcedure or surgery
neoadjuvant surgery for breast cancer
pazopanib monotherapyDrug
6 months of treatment with pazopanib monotherapy
| Study group | Role | What they receive |
|---|---|---|
| Treatment Arm | Experimental | Preoperative
Cycles 1-4 Doxorubicin 60 mg/m2 IV over 15 minutes + Cyclophosphamide 600 mg/m2 IV over 30 minutes of Day 1 every 21 days
followed by:
Cycles 5-8 Paclitaxel 80 mg/m2 IV over 60 minutes (Days 1, 8, and 15) every 28 days in combination with pazopanib (800 mg) PO once daily (2 tablets taken at the same time each day either 1 hour before or 2 hours after a meal) Daily beginning on Day 1 of the first paclitaxel cycle Until 7 days before surgery
Followed by Surgery
Postoperative Pazopanib 800 mg PO once daily (2 tablets taken at the same time each day either 1 hour before or 2 hours after a meal) Daily beginning 4-6 weeks after surgery 6 months from first postoperative dose Receives: Drug: doxorubicin + cyclophosphamide; Drug: paclitaxel + pazopanib; Procedure: surgery; Drug: pazopanib monotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Pathologic Complete Response (pCR) in the Breast and Nodes
pCR was defined as no histologic evidence of invasive tumor cells in the surgical breast specimen, axillary nodes, or sentinel node identified after neoadjuvant chemotherapy.
Measured: From the start of the study until the time of surgery (average of 221.9 days [standard deviation of 23.65 days] after study entry)
Secondary outcomes (10)
Number of Participants With Pathologic Complete Response (pCR) in the Breast
pCR was defined as no histologic evidence of invasive tumor cells in the surgical breast specimen.
Measured: From the start of the study until the time of surgery (average of 221.9 [standard deviation of 23.65 days] days after study entry)
Number of Participants With Clinical Complete Response (cCR) in the Breast and Nodes at the Completion of the Doxorubicin and Cyclophosphamide (AC) Period
cCR was determined by tumor assessments performed by palpation. All clinical response assessments were to be performed by physical examination of the breast and the axilla. cCR was defined as the resolution of all target and non-target lesions identified at Baseline and no new lesions or other signs of disease progression. The criteria to be used for the determination of progressive disease were at the investigator's discretion.
Measured: From the start of the study until an average of 86.2 days (standard deviation of 5.76 days) after study entry
Number of Participants With Clinical CR (cCR) in the Breast and Nodes at the Completion of the AC and Weekly Paclitaxel (WP) + Pazopanib Preoperative Periods
cCR was determined by tumor assessments performed by palpation. All clinical response assessments were to be performed by physical examination of the breast and the axilla. cCR was defined as the resolution of all target and non-target lesions identified at Baseline and no new lesions or other signs of disease progression. The criteria to be used for the determination of progressive disease were at the investigator's discretion.
Measured: From the start of the study until the preoperative evaluation (an average of 203.0 days [standard deviation of 23.19 days] after study entry)
Invasive Recurrence-free Interval (IRFI)
IRFI was assessed as the time from study entry until the diagnosis of the first invasive local (evidence of invasive/in situ breast cancer [except LCIS] in the ipsilateral breast [IB]/skin of the breast), regional (development of tumor in the ipsilateral [IP] internal mammary, IP supraclavicular, IP infraclavicular, and/or IP axillary nodes, as well as the soft tissue of the IP axilla, following surgery), or distant (evidence of tumor in all areas, with the exception of those described for local and regional recurrence) breast cancer recurrence during the 24 months after study entry.
Measured: up to 24 months after study entry
Number of Participants With Cardiac Toxicity (Per Common Terminology Criteria for Adverse Events Version 3) at the Completion of the AC Period
The number of participants with cardiac toxicity was defined as those who had cardiac events of Grades (G) 3 and 4 leftventricular dysfunction (LVD) (CTCAE Version 3.0) and/or who had definite or probable cardiac death. Grade refers to the severity of the AE: G 1, mild AE; G 2, moderate AE; G 3, severe AE; G 4, life-threatening/disabling AE; G 5, death related to the AE. A G3 LVD event is defined as symptomatic congestive heart failure (CHF) responsive to intervention. A G4 event is defined as poorly controlled refractory CHF; ventricular assist device or heart transplant indicated.
Measured: From the start of the study until the preoperative evaluation (an average of 86.2 days [standard deviation of 5.76 days] after study entry)
Number of Participants With Cardiac Toxicity (Per CTCAE Version 3) at the Completion of the AC and Weekly Paclitaxel (WP) + Pazopanib Preoperative Periods
The number of participants with cardiac toxicity was defined as those who had cardiac events of Grades (G) 3 and 4 leftventricular dysfunction (LVD) (CTCAE Version 3.0) and/or who had definite or probable cardiac death. Grade refers to the severity of the AE: G 1, mild AE; G 2, moderate AE; G 3, severe AE; G 4, life-threatening/disabling AE; G 5, death related to the AE. A G3 LVD event is defined as symptomatic congestive heart failure (CHF) responsive to intervention. A G4 event is defined as poorly controlled refractory CHF; ventricular assist device or heart transplant indicated.
Measured: From the start of the study until the preoperative evaluation (an average of 203.0 days [standard deviation of 23.19 days] after study entry).
Number of Participants With Cardiac Toxicity (Per CTCAE Version 3.0) During the Postoperative Pazopanib Period
The number of participants with cardiac toxicity was defined as those who had cardiac events of Grades (G) 3 and 4 leftventricular dysfunction (LVD) (CTCAE Version 3.0) and/or who had definite or probable cardiac death. Grade refers to the severity of the AE: G 1, mild AE; G 2, moderate AE; G 3, severe AE; G 4, life-threatening/disabling AE; G 5, death related to the AE. A G3 LVD event is defined as symptomatic congestive heart failure (CHF) responsive to intervention. A G4 event is defined as poorly controlled refractory CHF; ventricular assist device or heart transplant indicated.
Measured: From the start of the study until the end of the postoperative pazopanib period, which coincides with the start of the end of treatment period (an average of 310.8 days [standard deviation of 85.29 days] after study entry)
Participants With Normal Thyroid Stimulating Hormone (TSH) Levels at Baseline Who Had an Elevated TSH Level at Least Once During the Study and During the Individual Study Periods
The number of participants with normal thyroid function at Baseline who had an elevation in TSH during the study were recorded. TSH elevation was derived based on local laboratory ranges.
Measured: up to 24 months after study entry
Number of Participants With the Indicated Radiotherapy-related Complications
Measured: up to 24 months after study entry
Number of Participants With Recurrence Events
The number of participants with recurrence events during the 24 months after study entry are reported. A recurrence event is defined as invasive local (evidence of invasive/in situ breast cancer [except LCIS] in the ipsilateral breast [IB]/skin of the breast), regional (development of tumor in the ipsilateral [IP] internal mammary, IP supraclavicular, IP infraclavicular, and/or IP axillary nodes, as well as the soft tissue of the IP axilla, following surgery), or distant (evidence of tumor in all areas, with the exception of those described for local and regional recurrence) breast cancer recurrence during the 24 months after study entry.
Measured: up to 24 months after study entry
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2009 (estimated)
- Study startJul 2009
- Primary completionDec 2011
- Study completionApr 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Neoplasms, BreastStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 101 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- NSABP Foundation Inc
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00849472
- Sponsor's protocol ID
- 110264
- Other IDs
- NSABP FB-6
- Status last verified
- Dec 2013
- First submitted
- 12 Feb 2009
- Last updated
- 4 Mar 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Clinical Trial of Four Cycles of Doxorubicin and Cyclophosphamide Followed by Weekly Paclitaxel Given Concurrently With Pazopanib as Neoadjuvant Therapy Followed by Postoperative Pazopanib for Women With Locally Advanced Breast Cancer
- ClinicalTrials.gov ID
- NCT00849472
- Acronym / sponsor ID
- 110264
- Conditions
- Neoplasms, Breast
- Keywords
- Neoadjuvant Breast Cancer, Pazopanib (GW786034), NSABP Foundation, Inc., cyclophosphamide, Paclitaxel, Doxorubicin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 101 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Collaborators
- NSABP Foundation Inc
- Study start
- Jul 2009
- Primary completion
- Dec 2011 (actual)
- Study completion
- Apr 2013 (actual)
- First posted
- 23 Feb 2009 (estimated)
- Results
- Posted 9 Jan 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether the treatment of a doxorubicin in combination with cyclophosphamide followed by a combination of pazopanib in combination with paclitaxel prior to surgery results in a pathological complete response in females with breast cancer.
Detailed description
This is a phase II non-randomized, multi-center study aimed to evaluate the efficacy and safety of the combination of pazopanib and paclitaxel following treatment with cyclophosphamide and doxorubicin for the treatment of neoadjuvant breast cancer.
Patients will receive standard doses of AC every 21 days for 4 cycles. This will be followed by weekly paclitaxel 80 mg/m2 IV on Days 1, 8, and 15 every 28 days for 4 cycles given concurrently with pazopanib 800 mg PO daily starting with the first paclitaxel dose and continuing until 7 days before surgery. Clinical complete response rate will be determined by tumor assessments performed by palpation at two time points: following AC (before paclitaxel/pazopanib begins) and 2-4 weeks following the last dose of paclitaxel (before surgery). Following recovery from preoperative therapy, patients will undergo the clinically-indicated surgery. Pazopanib will resume 4-6 weeks after surgery and continue daily for 6 months of postoperative pazopanib therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment Arm | Experimental | Drug: doxorubicin + cyclophosphamide, Drug: paclitaxel + pazopanib, Procedure: surgery, Drug: pazopanib monotherapyPreoperative Cycles 1-4 Doxorubicin 60 mg/m2 IV over 15 minutes + Cyclophosphamide 600 mg/m2 IV over 30 minutes of Day 1 every 21 days followed by: Cycles 5-8 Paclitaxel 80 mg/m2 IV over 60 minutes (Days 1, 8, and 15) every 28 days in combination with pazopanib (800 mg) PO once daily (2 tablets taken at the same time each day either 1 hour before or 2 hours after a meal) Daily beginning on Day 1 of the first paclitaxel cycle Until 7 days before surgery Followed by Surgery Postoperative Pazopanib 800 mg PO once daily (2 tablets taken at the same time each day either 1 hour before or 2 hours after a meal) Daily beginning 4-6 weeks after surgery 6 months from first postoperative dose |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- The patient must have consented to participate and must have signed and dated an appropriate IRB-approved consent form that conforms to federal and institutional guidelines for the study treatment and submission of tumor and blood samples required for the FB-6 correlative science studies
- The ECOG performance status must be 0 or 1
- Patients must have the ability to swallow oral medication.
- The diagnosis of invasive adenocarcinoma of the breast must have been made by core needle biopsy or limited incisional biopsy.
- Patients must have ER analysis performed on the primary tumor prior to randomization. If ER analysis is negative, then PgR analysis must also be performed. (Patients are eligible with either hormone receptor-positive or hormone receptor-negative tumors.)
Key exclusion criteria (36 listed)
- Tumor that has been determined to be HER2-positive by immunohistochemistry (3+) or by FISH or CISH (positive for gene amplification), or has been determined to be HER2-equivocal and the investigator plans to administer trastuzumab or other targeted therapy.
- FNA alone to diagnose the primary breast cancer.
- Excisional biopsy or lumpectomy performed prior to study entry.
- Surgical axillary staging procedure prior to study entry.
- Definitive clinical or radiologic evidence of metastatic disease.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| doxorubicin + cyclophosphamide4 cycles of doxorubicin + cyclophosphamide followed by 4 cycles of paclitaxel + pazopanib. | Drug | Treatment Arm |
| paclitaxel + pazopanib4 cycles of paclitaxel + pazopanib | Drug | Treatment Arm |
| surgeryneoadjuvant surgery for breast cancer | Procedure or surgery | Treatment Arm |
| pazopanib monotherapy6 months of treatment with pazopanib monotherapy | Drug | Treatment Arm |
Primary outcome
Number of Participants With Pathologic Complete Response (pCR) in the Breast and Nodes
Time frame: From the start of the study until the time of surgery (average of 221.9 days [standard deviation of 23.65 days] after study entry)
pCR was defined as no histologic evidence of invasive tumor cells in the surgical breast specimen, axillary nodes, or sentinel node identified after neoadjuvant chemotherapy.
10 secondary outcomes
Number of Participants With Pathologic Complete Response (pCR) in the Breast
Time frame: From the start of the study until the time of surgery (average of 221.9 [standard deviation of 23.65 days] days after study entry)
Number of Participants With Clinical Complete Response (cCR) in the Breast and Nodes at the Completion of the Doxorubicin and Cyclophosphamide (AC) Period
Time frame: From the start of the study until an average of 86.2 days (standard deviation of 5.76 days) after study entry
Number of Participants With Clinical CR (cCR) in the Breast and Nodes at the Completion of the AC and Weekly Paclitaxel (WP) + Pazopanib Preoperative Periods
Time frame: From the start of the study until the preoperative evaluation (an average of 203.0 days [standard deviation of 23.19 days] after study entry)
Invasive Recurrence-free Interval (IRFI)
Time frame: up to 24 months after study entry
Number of Participants With Cardiac Toxicity (Per Common Terminology Criteria for Adverse Events Version 3) at the Completion of the AC Period
Time frame: From the start of the study until the preoperative evaluation (an average of 86.2 days [standard deviation of 5.76 days] after study entry)
Number of Participants With Cardiac Toxicity (Per CTCAE Version 3) at the Completion of the AC and Weekly Paclitaxel (WP) + Pazopanib Preoperative Periods
Time frame: From the start of the study until the preoperative evaluation (an average of 203.0 days [standard deviation of 23.19 days] after study entry).
Number of Participants With Cardiac Toxicity (Per CTCAE Version 3.0) During the Postoperative Pazopanib Period
Time frame: From the start of the study until the end of the postoperative pazopanib period, which coincides with the start of the end of treatment period (an average of 310.8 days [standard deviation of 85.29 days] after study entry)
Participants With Normal Thyroid Stimulating Hormone (TSH) Levels at Baseline Who Had an Elevated TSH Level at Least Once During the Study and During the Individual Study Periods
Time frame: up to 24 months after study entry
Number of Participants With the Indicated Radiotherapy-related Complications
Time frame: up to 24 months after study entry
Number of Participants With Recurrence Events
Time frame: up to 24 months after study entry
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
143 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing doxorubicin + cyclophosphamide, paclitaxel + pazopanib and surgery in people with Neoplasms, Breast, run by GlaxoSmithKline at 143 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Mar 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 143 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Jan 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Pathologic Complete Response (pCR) in the Breast and Nodes (time frame: From the start of the study until the time of surgery (average of 221.9 days [standard deviation of 23.65 days] after study entry)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2014.