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A Phase II Study of Using Panitumumab/Carboplatin/Paclitaxel (PaCT) Followed by Anthracycline-Containing Regimen (AC) for New Triple-Negative Inflammatory Breast Cancer (TN-IBC)

NCT02876107

Description:

The goal of this clinical research study is to learn if adding panitumumab to the combination of carboplatin and paclitaxel can help to control IBC when given before other standard chemotherapy and surgery. The safety of these drug combinations will also be studied. This is an investigational study. Panitumumab is FDA approved and commercially available for the treatment of EGFR-expressing metastatic colorectal cancer with disease progression. Paclitaxel, carboplatin, doxorubicin and cyclophosphamide are FDA approved and commercially available for the treatment of breast cancer. The addition of panitumumab to the combination of carboplatin and paclitaxel is investigational and currently being used for research purposes only. The study doctor can describe how the study drugs are designed to work. Up to 72 participants will be enrolled in this study. All will take part at MD Anderson.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title:A Phase II Study of Using Panitumumab/Carboplatin/Paclitaxel (PaCT) Followed by Anthracycline-Containing Regimen (AC) for New Triple-Negative Inflammatory Breast Cancer (TN-IBC)
  • Official Title:A Randomized Phase II Study of Neoadjuvant Carboplatin/Paclitaxel (CT) Versus Panitumumab/Carboplatin/Paclitaxel (PaCT) Followed by Anthracycline-Containing Regimen for Newly Diagnosed Primary Triple-Negative Inflammatory Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: 2016-0177
  • NCT ID: NCT02876107

Trial Conditions

  • Malignant Neoplasm of Breast

Trial Interventions

DrugSynonymsArms
PaclitaxelTaxolPaCT + Doxorubicin and Cyclophosphamide.
CarboplatinParaplatinPaCT + Doxorubicin and Cyclophosphamide.
PanitumumabVectibixPaCT + Doxorubicin and Cyclophosphamide.
DoxorubicinDoxorubicin HydrochlorideAdriamycin PFSAdriamycin RDFAdriamycinRubexPaCT + Doxorubicin and Cyclophosphamide.
CyclophosphamideCytoxanNeosarPaCT + Doxorubicin and Cyclophosphamide.

Trial Purpose

The goal of this clinical research study is to learn if adding panitumumab to the combination of carboplatin and paclitaxel can help to control IBC when given before other standard chemotherapy and surgery. The safety of these drug combinations will also be studied.

Detailed Description

Study Groups:

If participant is found to be eligible to take part in this study, they will be randomly assigned (as in the flip of a coin) to 1 of 2 study groups. Participant will have an equal (50/50) chance of being assigned to either group, and participant and the study staff will know what participant is receiving:

- If participant is in Group A, they will receive panitumumab, carboplatin, and paclitaxel, followed by doxorubicin and cyclophosphamide.

- If participant is in Group B, they will receive carboplatin and paclitaxel, followed by doxorubicin and cyclophosphamide.

Study Drug Administration:

Every study cycle will be 21 days.

Participant will receive paclitaxel by vein over about 1-3 hours on Days 1, 8, and 15 of Cycles 1-4.

Participant will receive carboplatin by vein over about 30 minutes on Day 1 of Cycles 1-4.

If participant is in Group A, they will also receive panitumumab by vein. Participant will first receive it over about 1 hour on Day 1 of a 1-week "pre-cycle." Participant will then receive it over about 30 minutes on Days 1, 8, and 15 of Cycles 1-4, before they receive paclitaxel.

Participant will then receive standard of care doxorubicin and cyclophosphamide by vein over about 90 minutes on Day 1 of Cycles 5-8.

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

Study Visits:

For both Groups A and B:

- Every day that participant receives the study drugs, and then at any time before surgery and after the last dose of doxorubicin and cyclophosphamide, blood (about 1½ to 3 tablespoons) will be drawn for routine tests.

- Before each cycle, and then at any time before surgery and after the last dose of doxorubicin and cyclophosphamide, participant will have a physical exam including a breast and lymph node exam.

- On Day 1 of Cycle 1, then 1 time before participant begins receiving doxorubicin and cyclophosphamide, and then 1 time before surgery, the study doctor will take pictures of both of participant's breasts.

- Before receiving any treatment, on Day 1 of Cycle 1, then 1 time before participant begins receiving doxorubicin and cyclophosphamide, and then 1 time before surgery , blood (about 5 tablespoons) will be drawn for cytokine testing.

- One (1) time before participant begins receiving doxorubicin and cyclophosphamide , they will have a mammogram of the involved breast and an ultrasound of the involved breast and lymph nodes. Participant may have a breast MRI if the doctor thinks it is needed.

If participant is in Group A, they will have a breast core biopsy before Day 1 of Cycle 1 for biomarker testing.

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

Surgery:

After participant has finished receiving doxorubicin and cyclophosphamide, they will have standard of care surgery. Participant will be given a separate consent form to read and sign.

During surgery, breast tissue samples will be collected to identify tumors for routine testing and for biomarker testing.

Length of Study:

Participant may continue taking the study drugs for up to 8 cycles. Participant will no longer be able to take the study drugs if the disease gets worse, if intolerable side effects occur, or if they are unable to follow study directions.

Patient's participation on the study will be over after the follow-up period.

Follow-Up:

About 1 month after surgery, participant will be asked about their health and any side effects they may have had. Participant may be asked during a routine clinic visit or they may be called by a member of the study staff. If participant is called, each call should last about 2 minutes.

One (1) time every year for at least 5 years after participant stops taking the study drugs, they will be contacted and asked about how they are doing. If participant is called, each call should last about 2 minutes. This may also be done in a regular clinic visit.

This is an investigational study. Panitumumab is FDA approved and commercially available for the treatment of epidermal growth factor receptor (EGFR)-expressing metastatic colorectal cancer with disease progression. Paclitaxel, carboplatin, doxorubicin and cyclophosphamide are FDA approved and commercially available for the treatment of breast cancer. The addition of panitumumab to the combination of carboplatin and paclitaxel is investigational and currently being used for research purposes only. The study doctor can describe how the study drugs are designed to work.

Up to 72 participants will be enrolled in this study. All will take part at MD Anderson.

Trial Arms

NameTypeDescriptionInterventions
PaCT + Doxorubicin and Cyclophosphamide.ExperimentalParticipants receive panitumumab, carboplatin, and paclitaxel (PaCT) followed by doxorubicin and cyclophosphamide. Breast core biopsy performed before Day 1 of Cycle 1 for biomarker testing. Paclitaxel given by vein on Days 1, 8, and 15 of Cycles 1-4. Carboplatin given by vein on Day 1 of Cycles 1-4. Panitumumab by vein on Day 1 of a 1-week "pre-cycle." Participants then receive it on Days 1, 8, and 15 of Cycles 1-4, before paclitaxel. Doxorubicin and cyclophosphamide given by vein on Day 1 of Cycles 5-8. Study cycle is 21 days. Before receiving doxorubicin and cyclophosphamide, mammogram of the involved breast and an ultrasound of the involved breast and lymph nodes performed. Study staff checks on participant about 1 month after surgery, and once each year for at least 5 years after participant stops taking the study drugs.
    • Paclitaxel
    • Carboplatin
    • Panitumumab
    • Doxorubicin
    • Cyclophosphamide
    CT + Adriamycin and Cyclophosphamide (AC)ExperimentalParticipants receive carboplatin and paclitaxel (CT) followed by adriamycin and cyclophosphamide (AC). Paclitaxel given by vein on Days 1, 8, and 15 of Cycles 1-4. Carboplatin given by vein on Day 1 of Cycles 1-4. Doxorubicin and cyclophosphamide given by vein on Day 1 of Cycles 5-8. Study cycle is 21 days. Before receiving doxorubicin and cyclophosphamide, mammogram of the involved breast and an ultrasound of the involved breast and lymph nodes performed. Study staff checks on participant about 1 month after surgery, and once each year for at least 5 years after participant stops taking the study drugs.
      • Paclitaxel
      • Carboplatin
        • Doxorubicin
        • Cyclophosphamide

      Eligibility Criteria

      Inclusion Criteria:

      1. Patients must have histological confirmation of breast carcinoma.

      2. Patients must have IBC, confirmed according to international consensus criteria: a. Onset: Rapid onset of breast erythema, edema, and/or peau d'orange, and/or warm breast, with or without an underlying breast mass b. Duration: History of such findings no more than 6 months c. Extent: Erythema occupying at least 1/3 of whole breast d. Pathology: Pathologic confirmation of invasive carcinoma

      3. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

      4. Patients must have negative HER2 expression on IHC (defined as 0 or 1+) or fluorescence in situ hybridization (FISH) analysis. If HER2 is 2+, negative HER2 expression must be confirmed by FISH (HER2/cep17 ration <2, and/or copy number less than 6). ER and progesterone receptor (PgR) expression should be less than 10%.

      5. Patients must be 18 years of age or older.

      6. Patients have left ventricular ejection fraction (LVEF) >=50% by multigated acquisition scan (MUGA) or echocardiogram before study randomization

      7. Patients have adequate hematologic function: absolute neutrophil count (ANC) >=1.5 x 10^9/L, platelet count >=100 x 10^9/L, hemoglobin >= 9.0 g/dL.

      8. Patients have adequate hepatic function: aspartate aminotransferase (AST) =<3.0 x upper limit of normal (ULN), alanine aminotransferase (ALT) =< 3.0 x ULN, alkaline phosphatase (ALP) =< 2.5 x ULN, total bilirubin =<1.5 x ULN

      9. Patients have 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 in years) x (weight in kg) / (serum Cr x 72); female CrCl = (140 - age in years) x (weight in kg) x 0.85 / (serum Cr x 72).

      10. Patients have the ability and willingness to sign written informed consent.

      11. Patients of childbearing potential (women who are postmenopausal for <1 year, not surgically sterilized, or not abstinent), have a negative urine pregnancy test, and agree to the consistent and correct use of one of the following acceptable methods of birth control: male partner who is sterile before the female subject's entry into the study and is the sole sexual partner for that female subject; intrauterine device, oral contraception, or barrier methods, including diaphragm or condom with a spermicide

      Exclusion Criteria:

      1. Stage IV disease, if the metastatic sites are not amendable for local therapy (i.e. radiation and/or surgery), and are not candidates for breast surgery will not be eligible.

      2. History of radiotherapy for current breast cancer diagnosis.

      3. History of recent malignancies <5 years (except for cured non-melanomatous skin cancer or cured cervical carcinoma in situ)

      4. Known positive test(s) for human immunodeficiency virus infection, hepatitis C virus, acute or chronic active hepatitis B infection.

      5. 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.

      6. Other known other significant medical or psychiatric condition that would make assessment of toxicity or efficacy difficult.

      7. 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

      8. Patients with a peripheral neuropathy > grade 1.

      9. Patients with a history of New York Heart Association class 3 or 4 heart failure, or history of myocardial infarction, unstable angina, or cerebrovascular accident (CVA) within 6 months of protocol registration.

      10. Patients have a history of prior therapy with carboplatin.

      11. Patients have received a cumulative dose of doxorubicin of greater than 360 mg/m2 or epirubicin of greater than 640 mg/m2.

      12. Patients have had prior radiotherapy for primary breast carcinoma or axillary lymph nodes.

      13. Patients have history of diagnosed interstitial lung disease.

      Maximum Eligible Age:N/A
      Minimum Eligible Age:18 Years
      Eligible Gender:Female
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure:Complete Pathologic Response (pCR) Rate
      Time Frame:After 8 cycles. Each cycle is 21 days.
      Safety Issue:Yes
      Description:pCR assessed at the time of surgery. Breast tissue samples collected during surgery. A Chi-square test or Fisher's exact test used to compare the differences in pCR rate between the two treatment arms.

      Secondary Outcome Measures

      Measure:Disease-Free Survival (DFS) Rate
      Time Frame:5 years
      Safety Issue:Yes
      Description:Disease progression defined as rapid growth of multiple measurable, non-measurable, or new lesions, or at least a 20% increase in the sum of diameters of target (measurable) lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).

      Trial Keywords

      • Malignant neoplasm of breast
      • Breast cancer
      • Newly diagnosed primary triple-negative inflammatory breast cancer
      • Inflammatory breast cancer
      • IBC
      • TN-IBC
      • Breast biopsy
      • Mammogram
      • Ultrasound
      • Paclitaxel
      • Taxol
      • Carboplatin
      • Paraplatin
      • Panitumumab
      • Vectibix
      • Doxorubicin
      • Doxorubicin Hydrochloride
      • Adriamycin PFS
      • Adriamycin RDF
      • Adriamycin
      • Rubex
      • Cyclophosphamide
      • Cytoxan
      • Neosar