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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)

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ClinicalTrials.gov Identifier: NCT02876107
Recruitment Status : Recruiting
First Posted : August 23, 2016
Last Update Posted : July 26, 2018
Sponsor:
Collaborator:
Amgen
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Tracking Information
First Submitted Date  ICMJE August 18, 2016
First Posted Date  ICMJE August 23, 2016
Last Update Posted Date July 26, 2018
Actual Study Start Date  ICMJE October 2016
Estimated Primary Completion Date October 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 18, 2016)
Complete Pathologic Response (pCR) Rate [ Time Frame: After 8 cycles. Each cycle is 21 days. ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02876107 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 18, 2016)
Disease-Free Survival (DFS) Rate [ Time Frame: 5 years ]
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).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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
Brief Summary

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.

Detailed Description

Study Groups:

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

  • If you are in Group A, you will receive panitumumab, carboplatin, and paclitaxel, followed by doxorubicin and cyclophosphamide.
  • If you are in Group B, you will receive carboplatin and paclitaxel, followed by doxorubicin and cyclophosphamide.

Study Drug Administration:

Every study cycle will be 21 days.

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

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

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

You 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 you receive 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, you will have a physical exam including a breast and lymph node exam.
  • On Day 1 of Cycle 1, then 1 time before you begin receiving doxorubicin and cyclophosphamide, and then 1 time before surgery, the study doctor will take pictures of both of your breasts.
  • Before receiving any treatment, on Day 1 of Cycle 1, then 1 time before you begin receiving doxorubicin and cyclophosphamide, and then 1 time before surgery , blood (about 5 tablespoons) will be drawn for cytokine testing.
  • One (1) time before you begin receiving doxorubicin and cyclophosphamide , you will have a mammogram of the involved breast and an ultrasound of the involved breast and lymph nodes. You may have a breast MRI if the doctor thinks it is needed.

If you are in Group A, you 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 you have finished receiving doxorubicin and cyclophosphamide, you will have standard of care surgery. You 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:

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

Your participation on the study will be over after the follow-up period.

Follow-Up:

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

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

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Malignant Neoplasm of Breast
Intervention  ICMJE
  • Procedure: Breast Core Biopsy
    Breast core biopsy performed before Day 1 of Cycle 1 for biomarker testing.
  • Drug: Paclitaxel
    80 mg/m2 given by vein on Days 1, 8, and 15 of Cycles 1-4.
    Other Name: Taxol
  • Drug: Carboplatin
    5 AUC given by vein on Day 1 of Cycles 1-4.
    Other Name: Paraplatin
  • Drug: Panitumumab
    2.5 mg/kg 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.
    Other Name: Vectibix
  • Drug: Doxorubicin
    60 mg/m2 given by vein on Day 1 of Cycles 5-8.
    Other Names:
    • Doxorubicin Hydrochloride
    • Adriamycin PFS
    • Adriamycin RDF
    • Adriamycin
    • Rubex
  • Drug: Cyclophosphamide
    600 mg/m given by vein on Day 1 of Cycles 5-8.
    Other Names:
    • Cytoxan
    • Neosar
  • Procedure: Mammogram
    Before receiving doxorubicin and cyclophosphamide, a mammogram of the involved breast performed.
  • Procedure: Ultrasound
    Before receiving doxorubicin and cyclophosphamide, an ultrasound of the involved breast and lymph nodes performed.
  • Other: Follow Up
    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.
Study Arms  ICMJE
  • Experimental: PaCT + Doxorubicin and Cyclophosphamide.

    Participants 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.

    Interventions:
    • Procedure: Breast Core Biopsy
    • Drug: Paclitaxel
    • Drug: Carboplatin
    • Drug: Panitumumab
    • Drug: Doxorubicin
    • Drug: Cyclophosphamide
    • Procedure: Mammogram
    • Procedure: Ultrasound
    • Other: Follow Up
  • Experimental: CT + Adriamycin and Cyclophosphamide (AC)

    Participants receive carboplatin and paclitaxel (CT) followed by doxorubicin 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.

    Interventions:
    • Drug: Paclitaxel
    • Drug: Carboplatin
    • Drug: Doxorubicin
    • Drug: Cyclophosphamide
    • Procedure: Mammogram
    • Procedure: Ultrasound
    • Other: Follow Up
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 18, 2016)
72
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 2024
Estimated Primary Completion Date October 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 ECOG performance status of 0-1.
  4. Patients must have negative HER2 expression on IHC (defined as 0 or 1+) or 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 PgR expression should be less than 10%.
  5. Patients must be 18 years of age or older.
  6. Patients have 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 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 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Naoto Ueno, MD, PHD 713-792-2817
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02876107
Other Study ID Numbers  ICMJE 2016-0177
NCI-2017-00619 ( Registry Identifier: NCI CTRP )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party M.D. Anderson Cancer Center
Study Sponsor  ICMJE M.D. Anderson Cancer Center
Collaborators  ICMJE Amgen
Investigators  ICMJE
Principal Investigator: Naoto Ueno, MD, PHD M.D. Anderson Cancer Center
PRS Account M.D. Anderson Cancer Center
Verification Date July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP