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Panitumumab and Pembrolizumab in Combination With Neoadjuvant Chemotherapy for the Treatment of Stage III-IV Triple Negative Breast Cancer

Primary Purpose

Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8, Anatomic Stage IIIB Breast Cancer AJCC v8

Status
Withdrawn
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Carboplatin
Cyclophosphamide
Doxorubicin
Paclitaxel
Panitumumab
Pembrolizumab
Sponsored by
M.D. Anderson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Anatomic Stage III Breast Cancer AJCC v8

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Ability to understand and the willingness to provide written informed consent for the trial
  • Female or male and >= 18 years of age
  • Histological confirmation of invasive breast cancer. All histologic subtypes are eligible
  • Clinical diagnosis of IBC and amenable to breast surgery

    • Cohort 1, de novo stage IV (safety run-in)
    • Cohort 2, stage III or de novo stage IV
  • Known estrogen receptor (ER), progesterone receptor (PR), and HER2 status defined as triple negative breast cancer (TNBC)

    • TNBC as defined as ER and PR =< 10% by immunohistochemistry, and HER2-negative (defined as IHC 0, 1+, or 2+ and FISH negative. The positivity of FISH is determined as per ASCO/CAP guideline).
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
  • Absolute neutrophil count (ANC) >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Hemoglobin (Hgb) >= 10g/dL
  • Creatinine levels < 1.5 x upper limit of normal (ULN)
  • Total bilirubin =< 1.5 x ULN
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN or =< 5 x ULN for patients with liver metastases
  • Subjects of childbearing potential should be willing to use effective methods of birth control or be surgically sterile or abstain from heterosexual activity for the course of the study through at least 4 months after the last dose of study drug. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year. Effective methods of birth control include 1) Use of hormonal birth control methods: pills, shots/injections, implants (placed under the skin by a health care provider), or patches (placed on the skin); 2) Intrauterine devices (IUDs); 3) Using 2 barrier methods (each partner must use 1 barrier method) with a spermicide. Males must use the male condom (latex or other synthetic material) with spermicide. Females must choose either a Diaphragm with spermicide, or Cervical cap with spermicide, or a sponge (spermicide is already in the contraceptive sponge)
  • Negative serum or urine pregnancy test for subjects of childbearing potential

Exclusion Criteria:

  • Any other previous or concurrent antitumor therapies for the current cancer diagnosis event
  • Known diagnosis of immunodeficiency, which defined as on chronic systemic steroid therapy or any other forms of immunosuppressive therapy in excess of the equivalent of prednisolone 10 mg once daily
  • History of malignancy (other than breast cancer) within 5 years, except basal cell carcinoma or squamous cell carcinoma of the skin, melanoma in-situ or in situ cervical cancer that has undergone potentially curative therapy
  • Known active central nervous system metastases and/or carcinomatous meningitis
  • Known significant cardiovascular disease, such as a history of myocardial infarction, acute coronary syndrome, congestive heart failure (CHF) New York Heart Association (NYHA) class II-IV, or history of CHF NYHA class III or IV
  • Ejection fraction < 50% by echocardiogram (ECHO) or multigated acquisition scan (MUGA)
  • Known active or uncontrolled autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids chronic corticosteroid use or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjogren's syndrome will not be excluded from the study
  • History of (non-infectious) pneumonitis that required steroids or has a current diagnosis of pneumonitis
  • An active infection requiring systemic therapy
  • Gastrointestinal tract disease or defect or previous history of colitis or inflammatory bowel disease including Crohn's disease and ulcerative colitis
  • Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • Known history of human immunodeficiency virus
  • Known active hepatitis B or hepatitis C
  • Received a live vaccine within 30 days before the first dose of trial treatment

Sites / Locations

  • M D Anderson Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (panitumumab,pembrolizumab,neoajuvant chemotherapy)

Arm Description

CYCLES 1-4: Patients receive pembrolizumab IV over 30 minutes and panitumumab IV over 30-60 minutes on day 1 of cycle 0. Cycle 0 continues for 7 days in the absence of disease progression or unacceptable toxicity. Patients then receive panitumumab IV over 30-60 minutes on days 1, 8, and 15 of cycles 1-3 and days 1 and 8 of cycle 4, pembrolizumab IV over 30 minutes on day 1 of cycles 2-4, paclitaxel IV over 1-3 hours on days 1, 8, and 15 of cycles 1-4, and carboplatin IV over 30 minutes on day 1, 8 and 15 of cycles 1-4. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. CYCLES 5-8: Patients receive standard of care treatment, including pembrolizumab IV over 30 minutes, doxorubicin IV over 15 minutes and cyclophosphamide IV over 30 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

The ( pCR ) rate pathological complete response, defined as the absence of invasive carcinoma in the breast and the lymph nodes.

Secondary Outcome Measures

Full Information

First Posted
December 14, 2021
Last Updated
July 26, 2023
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT05177796
Brief Title
Panitumumab and Pembrolizumab in Combination With Neoadjuvant Chemotherapy for the Treatment of Stage III-IV Triple Negative Breast Cancer
Official Title
Enhancing Immunotherapy by Targeting the EGFR Pathway in Inflammatory Breast Cancer: A Phase II Study of Panitumumab (PmAb) and Pembrolizumab (Pembro) in Combination With Neoadjuvant Chemotherapy (NAC) in Patients With Newly Diagnosed Triple Negative Inflammatory Breast Cancer (TN-IBC)
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Withdrawn
Why Stopped
0 participants recruited
Study Start Date
March 11, 2022 (Actual)
Primary Completion Date
July 26, 2023 (Anticipated)
Study Completion Date
July 26, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This phase II trial tests whether panitumumab and pembrolizumab in combination with standard of care chemotherapy before surgery (neoadjuvant) works to shrink tumors in patients with stage III-IV triple negative breast cancer. Panitumumab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as paclitaxel, carboplatin, doxorubicin, and cyclophosphamide 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 and pembrolizumab in combination with neoadjuvant chemotherapy may kill more tumor cells in patients with triple negative breast cancer.
Detailed Description
PRIMARY OBJECTIVE: I. To determine the pathological complete response (pCR rate) of the proposed combination in patients with newly diagnosed triple-negative inflammatory breast cancer (TN-IBC). SECONDARY OBJECTIVES I. To evaluate the surgical complication rate after the completion of the proposed treatment. II. To determine the change of EGR1 related to the efficacy of proposed treatment. (Key Secondary Objective) III. To determine the immunological change of tumor microenvironment (TME) related to the efficacy of proposed treatment. (Key Secondary Objective) IV. To define the cutoff or threshold of changes of EGR1, which will correlate with the pCR. V. To define the cutoff or threshold of immunological changes of TME, which will correlate with the pCR. VI. To determine two-year recurrence-free survival (RFS) rates. VII. To determine two-year overall survival (OS) rates. VIII. To determine the safety and tolerability. IX. To determine the predictive biomarkers to predict the therapeutic response. (correlative study) OUTLINE: CYCLES 1-4: Patients receive pembrolizumab intravenously (IV) over 30 minutes and panitumumab IV over 30-60 minutes on day 1 of cycle 0. Cycle 0 continues for 7 days in the absence of disease progression or unacceptable toxicity. Patients then receive panitumumab IV over 30-60 minutes on days 1, 8, and 15 of cycles 1-3 and days 1 and 8 of cycle 4, pembrolizumab IV over 30 minutes on day 1 of cycles 2-4, paclitaxel IV over 1-3 hours on days 1, 8, and 15 of cycles 1-4, and carboplatin IV over 30 minutes on day 1, 8 and 15 of cycles 1-4. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. CYCLES 5-8: Patients receive standard of care treatment, including pembrolizumab IV over 30 minutes, doxorubicin IV over 15 minutes and cyclophosphamide IV over 30 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 and 90 days, then every 6 months for 2 years from date of surgery.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8, Anatomic Stage IIIB Breast Cancer AJCC v8, Anatomic Stage IIIC Breast Cancer AJCC v8, Anatomic Stage IV Breast Cancer AJCC v8, Breast Inflammatory Carcinoma, Invasive Breast Carcinoma, Prognostic Stage III Breast Cancer AJCC v8, Prognostic Stage IIIA Breast Cancer AJCC v8, Prognostic Stage IIIB Breast Cancer AJCC v8, Prognostic Stage IIIC Breast Cancer AJCC v8, Prognostic Stage IV Breast Cancer AJCC v8, Triple-Negative Breast Carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (panitumumab,pembrolizumab,neoajuvant chemotherapy)
Arm Type
Experimental
Arm Description
CYCLES 1-4: Patients receive pembrolizumab IV over 30 minutes and panitumumab IV over 30-60 minutes on day 1 of cycle 0. Cycle 0 continues for 7 days in the absence of disease progression or unacceptable toxicity. Patients then receive panitumumab IV over 30-60 minutes on days 1, 8, and 15 of cycles 1-3 and days 1 and 8 of cycle 4, pembrolizumab IV over 30 minutes on day 1 of cycles 2-4, paclitaxel IV over 1-3 hours on days 1, 8, and 15 of cycles 1-4, and carboplatin IV over 30 minutes on day 1, 8 and 15 of cycles 1-4. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. CYCLES 5-8: Patients receive standard of care treatment, including pembrolizumab IV over 30 minutes, doxorubicin IV over 15 minutes and cyclophosphamide IV over 30 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Other Intervention Name(s)
Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
(-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Doxorubicin
Other Intervention Name(s)
Adriablastin, Hydroxydaunomycin, Hydroxyl Daunorubicin, Hydroxyldaunorubicin
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Other Intervention Name(s)
Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
Panitumumab
Other Intervention Name(s)
ABX-EGF, ABX-EGF Monoclonal Antibody, ABX-EGF, Clone E7.6.3, E7.6.3, Human IgG2K Monoclonal Antibody, MoAb ABX-EGF, MoAb E7.6.3, Monoclonal Antibody ABX-EGF, Monoclonal Antibody E7.6.3, Vectibix
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
Keytruda, Lambrolizumab, MK-3475, SCH 900475
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
The ( pCR ) rate pathological complete response, defined as the absence of invasive carcinoma in the breast and the lymph nodes.
Time Frame
through study completion, an average of 1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Ability to understand and the willingness to provide written informed consent for the trial Female or male and >/= 18 years of age Histological confirmation of invasive breast cancer. All histologic subtypes are eligible. Clinical diagnosis of IBC and amenable to breast surgery Cohort 1 (safety run-in), stage III or de novo stage IV Cohort 2, stage III or de novo stage IV Known ER, PR, and HER2 status defined as triple negative breast cancer (TNBC). TNBC is defined as ER and PR ≤ 10% by immunohistochemistry, and HER2 negative (defined as IHC 0, 1+, or 2+ and FISH negative. The positivity of FISH is determined as per ASCO/CAP guideline.(46) ECOG performance status of 0-1. Adequate organ function as determined by the following laboratory values: ANC >/= 1,500/mcL Platelets >/= 100,000/mcL Hgb >/= 10g/dL Creatinine levels <1.5 x ULN Total bilirubin </= 1.5 x ULN, ALT and AST </= 2.5 x ULN or </=5 x ULN for patients with liver metastases Subjects of childbearing potential should be willing to use effective methods of birth control or be surgically sterile or abstain from heterosexual activity for the course of the study through at least 4 months after the last dose of study drug. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for >1 year. Effective methods of birth control include 1) Use of hormonal birth control methods: pills, shots/injections, implants (placed under the skin by a health care provider), or patches (placed on the skin); 2) Intrauterine devices (IUDs); 3) Using 2 barrier methods (each partner must use 1 barrier method) with a spermicide. Males must use the male condom (latex or other synthetic material) with spermicide. Females must choose either a Diaphragm with spermicide, or Cervical cap with spermicide, or a sponge (spermicide is already in the contraceptive sponge). Negative serum or urine pregnancy test for subjects of childbearing potential. Exclusion Criteria: Any other previous or concurrent antitumor therapies for the current cancer diagnosis event. Known diagnosis of immunodeficiency, which defined as on chronic systemic steroid therapy or any other forms of immunosuppressive therapy in excess of the equivalent of prednisolone 10 mg once daily. History of malignancy (other than breast cancer) within 5 years, except basal cell carcinoma or squamous cell carcinoma of the skin, melanoma in-situ or in situ cervical cancer that has undergone potentially curative therapy. Known active central nervous system metastases and/or carcinomatous meningitis. Known significant cardiovascular disease, such as a history of myocardial infarction, acute coronary syndrome, Congestive heart failure (CHF) New York Heart Association (NYHA) Class II-IV, or history of CHF NYHA Class III or IV. Ejection fraction < 50% by ECHO or MUGA. Known active or uncontrolled autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids chronic corticosteroid use or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study. History of (non-infectious) pneumonitis that required steroids or has a current diagnosis of pneumonitis. An active infection requiring systemic therapy. Gastrointestinal tract disease or defect or previous history of colitis or inflammatory bowel disease including Crohn's disease and ulcerative colitis. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. Known history of Human Immunodeficiency Virus. Known active Hepatitis B or Hepatitis C Received a live vaccine within 30 days before the first dose of trial treatment.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Azadeh Nasrazad, MD,PHD
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.mdanderson.org
Description
M D Anderson Cancer Center

Learn more about this trial

Panitumumab and Pembrolizumab in Combination With Neoadjuvant Chemotherapy for the Treatment of Stage III-IV Triple Negative Breast Cancer

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