Panitumumab, Nab-paclitaxel and Carboplatin for HER2 Negative Inflammatory Breast Cancer

Sponsor

M.D. Anderson Cancer Center (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT01036087

Collaborator

Celgene Corporation (Industry), Amgen (Industry)

Enrollment

Location

Arm

144

Anticipated Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The goal of this clinical research study is to learn how effective the combination of chemotherapy including both panitumumab, Abraxane (nab-paclitaxel), and carboplatin (PNC) and fluorouracil, epirubicin, and cyclophosphamide (FEC) used before surgery for the treatment of IBC is. The safety of PNC combination will also be studied.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Panitumumab Drug: Nab-paclitaxel Drug: Carboplatin Drug: 5-Fluorouracil Drug: Epirubicin Drug: Cyclophosphamide	Phase 2

Detailed Description

Study Drugs:

Panitumumab is designed to prevent or slow down the growth of tumor cells by blocking the proteins on the surface the cancer cell, called the epidermal growth factor receptor (EGFR).

Nab-paclitaxel is designed to kill tumor cells by binding a chemotherapy drug paclitaxel to albumin, a protein made by the liver. The albumin gets into the cancer cell and releases the paclitaxel directly to the tumor.

Carboplatin is designed to stop or slow cancer cells from growing by damaging the RNA or DNA (the genetic material of cells) that tells the tumor cells to grow.

5-fluorouracil, epirubicin, and cyclophosphamide each work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

Study Drug Administration:

On Day 1 of Week 1, you will receive panitumumab through a needle in your vein over 60 minutes.

After Week 1, you will receive a total of 4 cycles of PNC. Each cycle is 4 weeks.

During Cycles 1-3 (Weeks 2-13), you will receive PNC by vein once a week for 3 weeks, followed by a week of rest. You will receive PNC through a needle in your vein. The infusion will take 90 minutes.

During Cycle 4 (Week 14 to 17), you will receive PNC on Day 1 of Weeks 14 and 15. On Day 1 of Week 16, you will receive only carboplatin and nab-paclitaxel.

Starting on Day 1 of Week 18, you will receive FEC through a needle in your vein. The infusion will take 90 minutes. You will receive a total of 4 cycles, each 3 weeks long, over 12 weeks.

Surgery:

After you have completed both PNC and FEC treatments, you will have the standard of care surgery performed. You will be given a separate consent form to read and sign.

During surgery, breast tissue samples will be collected to identify tumors as routine procedure.

Study Visits:

Each week that you receive PNC or FEC therapy, before each dose of chemotherapy, blood (about 1 1/2 tablespoons) will be drawn for routine tests.

Before Week 2, an optional breast core biopsy will be performed to collect tumor samples for biomarker testing

On Week 2, every 4 weeks after that until the end of PNC, and again before FEC, the following tests and procedures will be performed before each dose of chemotherapy.

You will have a physical exam, including measurement of your vital signs and weight, and breast exam.
Blood (about 1 1/2 tablespoons) will be drawn for routine tests.
You will be asked how well you are able to perform the normal activities of daily living (performance status).

During Weeks 2 and 9, and before FEC therapy, the study doctor will take pictures of both of your breasts.

Before FEC (after Cycle 4 of PNC) and again before surgery, the following tests and procedures will be performed:

To check the status of the disease, imaging studies including mammogram, breast MRI, breast ultrasound, and digital photograph will be performed.
You will have a physical exam, including vital signs, weight, and breast exam
Blood (about 3 tablespoons) will be drawn for routine tests.
You will be asked about any symptoms that you may have.
The ECGs and ECHO/MUGA scans will be repeated, when the doctor thinks it is necessary.

This schedule may be changed if the study doctor thinks that it is necessary.

Length of the study:

You may remain on study treatment for up to 10 months. You will be taken off study early if the disease gets worse or you experience intolerable side effects.

This is an investigational study. Panitumumab is FDA approved and commercially available for the treatment of EGFR-expressing metastatic colorectal cancer with disease progression. It's use in this study is considered to be investigational.

Nab-paclitaxel is FDA approved and commercially available for the treatment of breast cancer after the failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy. The use of Nab-paclitaxel in this study is considered to be investigational.

Carboplatin is FDA approved and commercially available for the treatment of IBC.

FEC is FDA approved for breast cancer in general, but not specifically for inflammatory breast cancer.

The use of PNC and FEC together before surgery is investigational.

Up to 40 patients will take part in this study. All will be enrolled at MD Anderson.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase II Study of Panitumumab, Nab-paclitaxel, and Carboplatin for Patients With Primary Inflammatory Breast Cancer (IBC) Without HER2 Overexpression

Actual Study Start Date :

Nov 1, 2010

Anticipated Primary Completion Date :

Nov 1, 2022

Anticipated Study Completion Date :

Nov 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PNC + FEC PNC = Panitumumab + Nab-paclitaxel + Carboplatin, and FEC = 5-fluorouracil, epirubicin, and cyclophosphamide	Drug: Panitumumab 2.5 mg/kg IV on Day 1 of Week 1 over 60 minutes, followed by 2.5 mg/kg weekly Weeks 2-12. Other Names: Vectibix Drug: Nab-paclitaxel 100 mg/m2 IV over 30 min on Day 1 of Weeks 2-13 over 30 minutes. Other Names: Paclitaxel (protein-bound) Abraxane ABI-007 Drug: Carboplatin AUC 2 IV over 30 min on Day 1 of Weeks 2-13 after completion of Abraxane through separate IV line. Other Names: Paraplatin Drug: 5-Fluorouracil 500 mg/m2 IV every 3 weeks, starting on Day 1 of Week 14 (4 cycles, each 3 weeks long, over 12 weeks). Other Names: 5-FU Adrucil Efudex Drug: Epirubicin 100 mg/m2 IV over 30 min every 3 weeks starting on Day 1 of Week 14 (4 cycles, each 3 weeks long, over 12 weeks). Other Names: Ellence Drug: Cyclophosphamide 500 mg/m2 IV every 3 weeks starting on Day 1 of Week 14 (4 cycles, each 3 weeks long, over 12 weeks). Other Names: Cytoxan Neosar

Arm

Intervention/Treatment

Experimental: PNC + FEC

PNC = Panitumumab + Nab-paclitaxel + Carboplatin, and FEC = 5-fluorouracil, epirubicin, and cyclophosphamide

Drug: Panitumumab

2.5 mg/kg IV on Day 1 of Week 1 over 60 minutes, followed by 2.5 mg/kg weekly Weeks 2-12.

Other Names:

Vectibix

Drug: Nab-paclitaxel

100 mg/m2 IV over 30 min on Day 1 of Weeks 2-13 over 30 minutes.

Other Names:

Paclitaxel (protein-bound)

Abraxane

ABI-007

Drug: Carboplatin

AUC 2 IV over 30 min on Day 1 of Weeks 2-13 after completion of Abraxane through separate IV line.

Other Names:

Paraplatin

Drug: 5-Fluorouracil

500 mg/m2 IV every 3 weeks, starting on Day 1 of Week 14 (4 cycles, each 3 weeks long, over 12 weeks).

Other Names:

5-FU

Adrucil

Efudex

Drug: Epirubicin

100 mg/m2 IV over 30 min every 3 weeks starting on Day 1 of Week 14 (4 cycles, each 3 weeks long, over 12 weeks).

Other Names:

Ellence

Drug: Cyclophosphamide

500 mg/m2 IV every 3 weeks starting on Day 1 of Week 14 (4 cycles, each 3 weeks long, over 12 weeks).

Other Names:

Cytoxan

Neosar

Outcome Measures

Primary Outcome Measures

Pathologic Complete Response (CR) Rate [Assessed after 14 weeks (following PNC and FEC preoperative chemotherapy treatment).]
Pathologic CR: No evidence of residual invasive tumor, including no residual tumor in the axillary lymph nodes.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histological confirmation of breast carcinoma. Pathologic evidence of dermal lymphatic invasion should be noted but not required.
Clinical diagnosis of IBC (presence of inflammatory changes in the involved breast, including diffuse erythema, heat, ridging, and peau d'orange).
/= Age 18
ECOG performance status </= 1
Adequate hematologic function: Absolute neutrophil count (ANC) >/= 1.5 x 109/L, Platelet count >/= 100 x 109/L, Hemoglobin >/= 9.0 g/dL
Adequate cardiac function (LVEF >/= 45%)
Adequate Renal function: Creatinine (Cr) </= 1.5 mg/dL x ULN, Creatinine clearance (CrCl) >/= 50 mL/min calculated by the Cockcroft-Gault method as follows: Male creatinine clearance = (140 - age) x (weight in Kg) / (serum Cr x 72) Female CrCl = (140 - age) x (weight in Kg) x 0.85 / (serum Cr x 72)
Adequate Hepatic function: Aspartate aminotransferase (AST) </= 2.5 x ULN • Alanine aminotransferase (ALT) </= 2.5 x ULN • Alkaline phosphatase (Alp) </= 2.5 x ULN.Total bilirubin </=1.5 x ULN
Ability and willingness to sign an informed consent form for this protocol
If female of childbearing potential (women who are post-menopausal < 1 year, not surgically sterilized, or not abstinent), pregnancy urine test is negative, and agrees to be consistent and correct use of one of the following acceptable methods of birth control: male partner who is sterile prior to the female subject entry into the study and is the sole sexual partner for that female subject; any intrauterine device (IUD) with a documented failure rate of less than 1% per year; oral contraception, or barrier methods, including diaphragm or condom with a spermicide.
Patients who have metastatic disease, if the metastatic sites are amendable for local therapy (i.e. radiation and/or surgery), and are candidates for breast surgery will be eligible,

Exclusion Criteria:

History of radiation or chemotherapy
HER2-positive breast carcinoma (IHC staining more than 3+ or HER2 gene amplification by FISH)
Recurrent breast cancer
History of other malignancies (except for cured non-melanomatous skin cancer or cured cervical carcinoma in situ, or malignancies with no evidence of disease and no treatment for >5 years)
Known positive test(s) for human immunodeficiency virus infection, hepatitis C virus, acute or chronic active hepatitis B infection
History of extensive interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or any evidence of extensive interstitial lung disease on baseline chest CT scan
Patient with other significant medical or psychiatric condition that would make assessment of toxicity or efficacy difficult.
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Peripheral neuropathy >= Gr II