Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Anti-Infective Agents

Paclitaxel

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

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

4 cycles of doxorubicin + cyclophosphamide followed by 4 cycles of paclitaxel + pazopanib.

doxorubicin + cyclophosphamide

paclitaxel + pazopanib

surgery

6 months of treatment with pazopanib monotherapy

pazopanib monotherapy

GSK Clinical Trials

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.

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.

Treatment With Pazopanib for Neoadjuvant Breast Cancer

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

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.

pCR was defined as no histologic evidence of invasive tumor cells in the surgical breast specimen.

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.

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.

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.

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.

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.

NSABP Foundation Inc

GlaxoSmithKline

Participants were treated with intravenous (IV) doxorubicin (60 milligrams per meters squared \[mg/m\^2\]) and cyclophosphamide (AC) (600 mg/m\^2) every 21 days for 4 cycles. This was followed by weekly paclitaxel (WP) 80 mg/m\^2 IV on Days 1, 8, and 15 every 28 days for 4 cycles given concurrently with oral pazopanib 800 mg (2 tablets taken at the same time each day, either 1 hour before or 2 hours after a meal) taken daily and continuing until 7 days before surgery. Pazopanib was resumed at the same oral dose 4-6 weeks after surgery and was continued daily for 6 months.

AC, Followed by Weekly Paclitaxel and Concurrent Pazopanib

Baseline Characteristic data are reported for members of the Treated Population, comprised of all participants who entered the study and received at least one dose of any study medication.

Age, Continuous

Sex: Female, Male

White - White/Caucasian/European Heritage (W/C/EH)

African American/African Heritage

White - Arabic/North African Heritage

Asian - South East Asian Heritage

American Indian (AI) or Alaskan Native (AN)

Asian - Central/South Asian Heritage

Asian - East Asian Heritage

AI or AN + White - W/C/EH

Race/Ethnicity, Customized

Estrogen receptor (ER) status positive

ER status negative

Progesterone receptor (PgR) status positive

PgR status negative

HER-2/NEU status positive

HER-2/NEU status negative

HER-2/NEU status equivocal (uncertain)

Baseline Characteristic (BC) data are reported for members of the Treated Population. Receptor status is used to determine a course of treatment. Participants with hormone-receptor positive tumors could have been treated with hormonal therapy. Human epidermal growth factor receptor-2 (HER-2) is also known as NEU. Each participant was to be assessed for each tumor hormone receptor.

Number of participants with a positive or negative status for the indicated hormone receptors

Positive

Negative

BC data are reported for members of the Treated Population. Estrogen causes certain breast cancers (called ER+ cancers) to grow; these cancer cells have ERs on their surfaces. ER+ and PR+ indicate ER and PR positivity; a minus sign indicates that cells are negative for receptors. A participant's hormone status determines treatment modalities.

Number of participants with the indicted hormonal status (ER+ and PR+ / ER- and PR-)

GSK Response Center

Evaluable Population: all participants who entered the study and received at least one dose of pazopanib.

Number of Participants With Pathologic Complete Response (pCR) in the Breast and Nodes

Number of Participants With Pathologic Complete Response (pCR) in the Breast

Number of Participants With Clinical Complete Response (cCR) in the Breast and Nodes at the Completion of the Doxorubicin and Cyclophosphamide (AC) Period

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

Overall Study Arm

Evaulable Population. Participants with recurrence before study entry were excluded from analysis.

Invasive Recurrence-free Interval (IRFI)

Treated Population: all participants who entered the study and received at least one dose of any study medication

Number of Participants With Cardiac Toxicity (Per Common Terminology Criteria for Adverse Events Version 3) at the Completion of the AC Period

Number of Participants With Cardiac Toxicity (Per CTCAE Version 3) at the Completion of the AC and Weekly Paclitaxel (WP) + Pazopanib Preoperative Periods

Treated Population: Only those members of the Treated Population who started the postoperative pazopanib period were assessed.

Number of Participants With Cardiac Toxicity (Per CTCAE Version 3.0) During the Postoperative Pazopanib Period

Elevated TSH at Least Once during the Study, n=101

AC Period, n=91

(WP) + Pazopanib Preoperative Periods, n=89

Surgery Period, n=78

Postoperative Pazopanib Period, n=36

Follow-up Period, n=33

Treated Population. Data are presented for only those participants who remained in the study during the indicated period and had their blood drawn for assessment.

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

Rash

Pneumonitis

Number of Participants With the Indicated Radiotherapy-related Complications

Evaulable Population, excluding participants with recurrence before study entry

Number of Participants With Recurrence Events

Participants (par.) were treated with intravenous (IV) doxorubicin (60 milligrams per meters squared \[mg/m\^2\]) and cyclophosphamide (AC) (600 mg/m\^2) every 21 days for 4 cycles. This was followed by weekly paclitaxel (WP) 80 mg/m\^2 IV on Days 1, 8, and 15 every 28 days for 4 cycles given concurrently with oral pazopanib 800 mg (2 tablets taken at the same time each day, either 1 hour before or 2 hours after a meal) taken daily and continuing until 7 days before surgery. Pazopanib was resumed at the same oral dose 4-6 weeks after surgery and was continued daily for 6 months.

Doxorubicin and Cyclophosphamide (AC)

Weekly Paclitaxel

Pazopanib Presurgery Treatment (PPT)

Pazopanib Postsurgery Treatment

Trastuzumab

Carboplatin

Pertuzumab

Antineoplastic Agents, Immunological

18 weeks (6 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab. Post treatment, patients will undergo surgery.

12 weeks (4 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab. Post 12 weeks, initiation of doxorubicin and cyclophosphamide for 4 cycles (6 weeks), followed by surgery.

Less than 18 weeks (6 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab, followed by initiation of doxorubicin and cyclophosphamide. Post treatment, patients will undergo surgery.

80 mg/m2 (or nab-paclitaxel 80-100 mg/m2) weekly

paclitaxel

Either every 3 weeks (8 mg/kg cycle 1 then 6 mg/kg cycles 2-4) or weekly (4 mg/kg week 1 then 2 mg/kg weeks 2-12)

every 3 weeks (840 mg cycle 1 then 420 mg cycles 2-4) or weeks 1 and 2 cycle 1 (420 mg each dose) during the first 3-6 weeks of treatment, then 420 mg day 1 of cycles 2-4.

AUC 2 administered weekly with no planned treatment breaks

carboplatin

Breast surgery

doxorubicin and cyclophosphamide (AC) every 2 or 3 weeks for 4 cycles

Dose-dense AC: Doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 IV day 1 every 2 weeks x 4 cycles

Standard AC: Doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 IV day 1 r every 3 weeks x 4 cycles

Howard Safran, MD

Neoadjuvant therapy is given to breast cancer patients whose cancers are relatively large or have spread to lymph nodes or both. The primary goal of this treatment is to prevent the cancer from coming back (recurring) elsewhere in the body, but if it makes the cancer in the breast and lymph nodes shrink it might be easier to remove. This could allow a patient to have a lumpectomy instead of a mastectomy and reduce the number of lymph nodes that the surgeon has to remove. In some cases, the neoadjuvant therapy works so well that it kills all of the cancer in the breast and lymph nodes. This is referred to as a pathologic complete response (pCR). Patients who achieve a pCR have a much lower risk of the cancer recurring elsewhere in their bodies.

Investigators aren't sure which chemotherapy drugs work best with the HER2-targeted drugs, and what combination of these drugs causes the fewest side effects.Thus, this study has two main goals:

1. To find out if treatment with wPCbTP, weekly paclitaxel and carboplatin given with trastuzumab and pertuzumab every 3 weeks, leads to as many pCRs as TCHP in patients with HER2-positive breast cancer, but has fewer side effects.
2. To find out if HER2-positive patients whose cancers are not responding well after 12 weeks of wPCbTP get a better response when they are switched to a doxorubicin-containing regimen called AC for 4 cycles (8-12 weeks).

Neoadjuvant Therapy in Clinical Stage I-III HER2-positive Breast Cancer.

Efficacy of Carboplatin and Paclitaxel With Trastuzumab and Pertuzumab (wPCbTP) and Switching to an Anthracycline-based Regimen (AC) in Non-responding Patients in Clinical Stage I-III HER2-positive Breast Cancer.

pCR is pathologic complete response defined as ypT0/isN0 on pathology report

Defined based on CTCAE version 4:

1. Neutropenia (grade\>2)
2. Thrombocytopenia (grade \>2)
3. Anemia (grade \>2)
4. Diarrhea (any grade, grade \>3)
5. Neuropathy (any grade, grade 2, grade \>3)
6. Vomiting (any grade, grade \>3)

Women and Infants Hospital of Rhode Island

Rhode Island Hospital

The Miriam Hospital

Brown University

Experimental: Optimal- 18 Weeks

Experimental: Sub-optimal With AC

Experimental: Sub-optimal no AC

Experimental: Optimal With AC

Total

Age, Categorical

Race and Ethnicity were not collected from any participant.

Race and Ethnicity Not Collected

United States

Region of Enrollment

No participants received less than 18 weeks (6 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab, followed by initiation of doxorubicin and cyclophosphamide.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Treatment With Pazopanib for Neoadjuvant Breast Cancer	NCT00849472	Neoplasms, Brea...	doxorubicin + c... paclitaxel + pa... surgery pazopanib monot...	18 Years -	GlaxoSmithKline
Neoadjuvant Therapy in Clinical Stage I-III HER2-positive Breast Cancer.	NCT02789657	Breast Cancer	paclitaxel Trastuzumab Pertuzumab carboplatin Breast surgery AC	18 Years -	Brown University

Spots Global Cancer Trial Database for neoadjuvant breast cancer