Clinical Trials /

Women's MoonShot: Neoadjuvant Treatment With PaCT for Patients With Locally Advanced TNBC

NCT02593175

Description:

This phase II trial studies how well panitumumab, carboplatin and paclitaxel work in treating patients with newly diagnosed triple negative breast cancer that is limited to the breast and possibly to the nearby lymph nodes (locally advanced). This treatment study is linked to NCI-2015-00191 protocol, which uses a baseline biopsy to determine the neoadjuvant therapy that matches the sub-type of triple negative breast cancer (TNBC). Immunotherapy with panitumumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving panitumumab, carboplatin and paclitaxel before surgery may be an effective treatment for breast cancer by making the tumor smaller and reducing the amount of normal tissue that needs to be removed.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Women's MoonShot: Neoadjuvant Treatment With PaCT for Patients With Locally Advanced TNBC
  • Official Title: Women's Triple-Negative First-Line Study: A Phase II Trial of Panitumumab, Carboplatin and Paclitaxel (PaCT) in Patients With Localized Triple-Negative Breast Cancer (TNBC) With Tumors Predicted Insensitive to Standard Neoadjuvant Chemotherapy

Clinical Trial IDs

  • ORG STUDY ID: 2015-0294
  • SECONDARY ID: NCI-2015-02183
  • SECONDARY ID: 2015-0294
  • NCT ID: NCT02593175

Conditions

  • Stage I Breast Cancer AJCC v7
  • Stage IA Breast Cancer AJCC v7
  • Stage IB Breast Cancer AJCC v7
  • Stage II Breast Cancer AJCC v6 and v7
  • Stage IIA Breast Cancer AJCC v6 and v7
  • Stage IIB Breast Cancer AJCC v6 and v7
  • Stage III Breast Cancer AJCC v7
  • Stage IIIA Breast Cancer AJCC v7
  • Stage IIIB Breast Cancer AJCC v7
  • Stage IIIC Breast Cancer AJCC v7
  • Triple-Negative Breast Carcinoma

Interventions

DrugSynonymsArms
CarboplatinBlastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, RibocarboTreatment (panitumumab, paclitaxel, carboplatin)
PaclitaxelAnzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol KonzentratTreatment (panitumumab, paclitaxel, carboplatin)
PanitumumabABX-EGF, ABX-EGF Monoclonal Antibody, ABX-EGF, Clone E7.6.3, MoAb ABX-EGF, Monoclonal Antibody ABX-EGF, VectibixTreatment (panitumumab, paclitaxel, carboplatin)

Purpose

This phase II trial studies how well panitumumab, carboplatin and paclitaxel work in treating patients with newly diagnosed triple negative breast cancer that is limited to the breast and possibly to the nearby lymph nodes (locally advanced). This treatment study is linked to NCI-2015-00191 protocol, which uses a baseline biopsy to determine the neoadjuvant therapy that matches the sub-type of triple negative breast cancer (TNBC). Immunotherapy with panitumumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving panitumumab, carboplatin and paclitaxel before surgery may be an effective treatment for breast cancer by making the tumor smaller and reducing the amount of normal tissue that needs to be removed.

Detailed Description

      PRIMARY OBJECTIVE:

      I. To evaluate the pathologic complete response (pCR), residual cancer burden (RCB)-0 and
      RCB-I rates of patients with localized TNBC who were treated with panitumumab, carboplatin
      and paclitaxel (PaCT) in the neoadjuvant setting.

      SECONDARY OBJECTIVES:

      I. To estimate progression free survival (PFS) distribution of localized TNBC patients who
      were non-responders to initial anthracycline and cyclophosphamide chemotherapy, and who were
      treated with the PaCT regimen in the neoadjuvant setting.

      II. Determine changes of epidermal growth factor receptor (EGFR) downstream biomarkers one
      week after 1 dose of panitumumab.

      III. Determine response rate after 4 cycles of PaCT using radiographic imaging. IV. Correlate
      pathologic response with EGFR expression as measured by immunohistochemistry (IHC).

      V. Determine toxicity associated to 4 cycles of PaCT in the neoadjuvant setting.

      VI. Compare pathologic response to 4 cycles of PaCT in EGFR overexpressing tumors versus
      (vs.) non-EGFR overexpressing tumors.

      VII. Compare pathologic response in tumors to 4 cycles of PaCT vs. 12 weeks of weekly
      paclitaxel (using data collected in conjunction with protocol 2014-0185).

      EXPLORATORY OBJECTIVES:

      I. Determine the correlation between EGFR expression by IHC and the presence of enhanced EGFR
      gene signatures at the time of initial tumor biopsy prior to neoadjuvant setting (NACT)
      (using gene expression data obtained from the protocol 2014-0185).

      II. Determine rates of pCR in patients with EGFR overexpressed tumors identified by gene
      signatures (using gene expression data obtained from protocol 2014-0185) and compare to pCR
      rates in non-EGFR overexpressed tumors.

      III. Determine the correlation between EGFR expression by IHC and the changes of EGFR
      downstream changes induced in surgery sample after completion of PaCT regimen.

      IV. Determine the change in programmed cell death ligand 1 (PD-L1) glycosylation induced by
      panitumumab, and correlation with efficacy.

      V. Determine the change after treatment in blood-based markers, if any, and use these to
      predict a response to panitumumab treatment.

      OUTLINE:

      Patients receive panitumumab intravenously (IV) over 30 minutes and paclitaxel IV over 30
      minutes on days 1, 8, and 15. Patients also receive carboplatin IV over 30 minutes on day 1.
      Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or
      unacceptable toxicity.

      After completion of study treatment, patients are followed up every 3-4 months.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (panitumumab, paclitaxel, carboplatin)ExperimentalPatients receive panitumumab IV over 30 minutes and paclitaxel IV over 30 minutes on days 1, 8, and 15. Patients also receive carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
  • Carboplatin
  • Paclitaxel
  • Panitumumab

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have an intact evaluable primary tumor or biopsy proven axillary node
             involvement with at least 1.0 centimeter (cm) smallest dimension based on imaging
             after neoadjuvant anthracycline-based chemotherapy and prior to initiation of
             neoadjuvant chemotherapy under this protocol; baseline measurements and evaluations
             must be obtained within 4 weeks of registration to the study; all areas of disease
             should be recorded in order to assess response and uniformity of response to therapy

          -  Triple-negative breast cancer defined as estrogen receptor (ER) < 10%; progesterone
             receptor (PR) < 10% by immunohistochemistry (IHC) and human epidermal growth factor
             receptor 2 (HER2) 0-1 positive (+) by IHC or 2+, fluorescence in situ hybridization
             (FISH) < 2, gene copy number < 4

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

          -  Patients must have received at least one dose of an anthracycline based neoadjuvant
             regimen; patients are eligible if therapy was discontinued due to disease progression
             or therapy intolerance

          -  Baseline multi-gated acquisition (MUGA) or echocardiogram showing left ventricular
             ejection fraction (LVEF) >= 50% within 6 weeks prior to initiation of neoadjuvant
             chemotherapy

          -  Serum creatinine =< 1.5 mg/dl

          -  Creatinine clearance (CrCl) >= 50 mL/min calculated by the Cockcroft-Gault method

          -  Absolute neutrophil count (ANC) >= 1500/mm^3

          -  Platelets >= 100,000/mm^3

          -  Hemoglobin >= 9.0 g/dL

          -  Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and
             serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 3.0 x
             upper limit of normal

          -  Alkaline phosphatase (Alp) =< 2.5 x upper limit of normal (ULN)

          -  Total bilirubin =< 1.5 x ULN

          -  Signed informed consent

        Exclusion Criteria:

          -  Patient is unwilling or unable to sign and date the Institutional Review Board (IRB)
             approved informed consent

          -  Patients with less than a 1.0 cm measurable residual disease after neoadjuvant
             anthracycline based chemotherapy

          -  Women that are pregnant or lactating

          -  Patients with a history of prior malignancy within 5 years of study entry with the
             exception of curatively treated non-melanomatous skin cancer or carcinoma in situ of
             the cervix or breast

          -  Patients with a history of stage IV or metastatic disease

          -  Any serious medical illness, other than that treated by this study, which would limit
             survival to less than 1 month or psychiatric illness which would limit informed
             consent

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

          -  Patients with a peripheral neuropathy > grade 1

          -  Patients with a history of serious cardiac events defined as: 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

          -  Patients with a history of PR prolongation or atrioventricular (AV) block

          -  Patients with a history of prior therapy with paclitaxel and/or carboplatin

          -  Patients who have received a cumulative dose of doxorubicin of greater than 360 mg/m^2
             or epirubicin of greater than 640 mg/m^2

          -  Patients who concurrently use hormonal therapy and/or concurrent radiation therapy

          -  Patients who had prior radiation therapy of the primary breast carcinoma or axillary
             lymph nodes

          -  Women of child-bearing potential (WOCBP), defined as all women physiologically capable
             of becoming pregnant, must use highly effective methods of contraception during the
             study and 8 weeks after; highly effective contraception methods include combination of
             any two of the following: placement of an intrauterine device (IUD) or intrauterine
             system (IUS), barrier methods of contraception: condom or occlusive cap (diaphragm or
             cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository, total
             abstinence or male/female sterilization; women are considered post-menopausal and not
             of child-bearing potential if they have had 12 months of natural (spontaneous)
             amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of
             vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without
             hysterectomy) or tubal ligation at least six weeks prior to treatment; in the case of
             oophorectomy alone, only when the reproductive status of the woman has been confirmed
             by follow up hormone level assessment is she considered not of child-bearing potential

          -  Male patients whose sexual partner(s) are WOCBP who are not willing to use adequate
             contraception, during the study and for 8 weeks after the end of treatment

          -  Negative serum or urine pregnancy test for women within 72 hours of receiving the
             first dose of the study medication for women of childbearing potential
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Pathologic compete response (pCR) (residual cancer burden [RCB]-0) or RCB-I response rates of patients with localized triple-negative breast cancer (TNBC) treated with panitumumab, carboplatin and paclitaxel (PaCT)
Time Frame:Up to 2 years
Safety Issue:
Description:Will estimate the proportion of patients with pCR (RCB-0) or RCB-I as the response rate along with an appropriate 95% confidence interval. Will estimate the proportion of patients in the remaining RCB categories with confidence intervals as well.

Secondary Outcome Measures

Measure:Progression free survival (PFS)
Time Frame:Time from enrollment to progression of disease (> 20% increase in tumor size) or death whichever comes first, assessed up to 2 years
Safety Issue:
Description:PFS distribution will be estimated using the Kaplan-Meier method.
Measure:Changes of EGFR levels
Time Frame:Baseline up to 1 week after 1 dose of panitumumab
Safety Issue:
Description:Potential biomarkers of response will be correlated with pathologic response to this treatment using appropriate statistical analyses for the biomarker of interest.
Measure:Pathologic complete response (pCR) (residual cancer burden [RCB]-0) or RCB-I response rates of patients treated with panitumumab, carboplatin and paclitaxel (PaCT)
Time Frame:Up to 4 courses (84 days)
Safety Issue:
Description:Assessed by radiographic imaging. The proportion of patients with pCR (RCB-0) or RCB-I as the response rate will be estimated along with an appropriate 95% confidence interval. The proportion of patients in the remaining RCB categories will be estimated with confidence intervals.
Measure:Overall survival (OS)
Time Frame:Up to 2 years after completion of study treatment
Safety Issue:
Description:OS distribution will be estimated using the Kaplan-Meier method.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Last Updated

April 14, 2021