Interferon Gamma-1b, Paclitaxel, Trastuzumab, and Pertuzumab in Treating Patients with HER-2 Positive Breast Cancer

Status: Active

Description

This phase I / II trial studies the side effects and best dose of interferon gamma-1b in combination with paclitaxel, trastuzumab, and pertuzumab in treating patients with HER-2 positive breast cancer. Interferon gamma-1b is a substance that can improve the body’s natural response and may interfere with the growth of tumor cells. Drugs used in chemotherapy, such as 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. Trastuzumab is a form of "targeted therapy" because it works by attaching itself to specific molecules (receptors) on the surface of cancer cells, known as HER2 receptors. When trastuzumab attaches to HER2 receptors, the signals that tell the cells to grow are blocked and the cancer cell may be marked for destruction by the body's immune system. Immunotherapy with monoclonal antibodies, such as pertuzumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving interferon gamma, paclitaxel, trastuzumab, and pertuzumab may work better than other therapies in treating HER-2 positive breast cancer.

Eligibility Criteria

Inclusion Criteria

  • Patients must have a histologically confirmed HER2 positive breast cancer (by immunohistochemistry [IHC] 3+ or fluorescence in situ hybridization [FISH] ratio >= 2.0) * Phase I: unresectable locally advanced or metastatic breast cancer * Phase II: clinical stage 1-3 early stage breast cancer with primary tumor is at least 1 cm measured by clinical exam or by radiologic breast imaging tests
  • Phase I: patients must be candidates to receive paclitaxel chemotherapy in combination with trastuzumab and pertuzumab * Phase II: no prior chemotherapy, radiation, or definitive therapeutic surgery (e.g., mastectomy, lumpectomy or axillary dissection) for this malignancy; patients who have had a prior sentinel lymph node biopsy for this malignancy are eligible * Note: patients who receive equal to or less than 1 cycle of therapy (up to 4 weeks) will be allowed to enroll on this trial
  • Patients who received tamoxifen or another selective estrogen receptor modulator (SERM) for the prevention or treatment of breast cancer or for other indications (e.g., osteoporosis, prior ductal carcinoma in situ [DCIS]), or who receive aromatase inhibitors for prevention or treatment of breast cancer, are eligible; patients who are hormone-receptor positive and who have received other hormonal agents for the treatment of breast cancer (e.g., Fulvestrant) are also eligible; tamoxifen therapy or other hormonal agents should be discontinued at least 1 week before the patient is started on study therapy
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Absolute neutrophil count (ANC) >= 1,500/uL (within 2 weeks of registration)
  • Platelets >= 100,000/uL (within 2 weeks of registration)
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN), except patients with Gilbert's syndrome in whom total bilirubin must be < 3.0 mg/dL (within 2 weeks of registration)
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x institutional upper limit of normal (within 2 weeks of registration)
  • Left ventricular ejection fraction (LVEF) ejection fraction (EF) >= of 50% (by echocardiogram or multigated acquisition [MUGA] scan within 12 weeks of registration)
  • Creatinine =< 1.5 x institutional upper limit of normal (ULN) (within 2 weeks of registration)
  • Electrocardiogram (ECG) - corrected QT (QTc) < 480 msec (within 2 weeks of registration)
  • Women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Ability to understand and willingness to sign a written informed consent document

Exclusion Criteria

  • Patients may not be receiving any other investigational agents during protocol therapy, or up to 14 days or 5 half-lives (whichever is longer) prior to beginning protocol therapy; there should be a least a 1-week interval between last dose of endocrine therapy and protocol therapy
  • Patients who have had chemotherapy or radiation therapy within 2 weeks prior to beginning protocol therapy
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, congenital prolonged QT syndrome, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Current use of corticosteroid therapy > 5 mg/day of prednisone or equivalent doses of other corticosteroids (topical, intranasal, and inhaled corticosteroids in standard doses and physiologic replacement for subjects with adrenal insufficiency are allowed)
  • Patients with known active or symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis; asymptomatic, treated, and/or stable brain metastases, as measured by subsequent radiologic evaluations at least two months apart, are permitted
  • Pregnant or breast feeding
  • Known human immunodeficiency virus (HIV)-positive
  • Known current or a history of hepatitis B or C virus, including chronic and dormant states, unless disease has been treated and confirmed cleared
  • Major surgery within 4 weeks of initiation of study drug
  • Second invasive malignancy requiring active treatment

Locations & Contacts

Florida

Tampa
Moffitt Cancer Center
Status: Active
Contact: Hyo Sook Han
Phone: 813-745-4933
Email: hyo.han@moffitt.org

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To evaluate the safety and tolerability of the combination of interferon gamma-1b (interferon [IFN]-gamma) with paclitaxel, trastuzumab and pertuzumab for 12 weeks and determine the recommended phase II dose (RP2D) in patients with metastatic breast cancer. (Phase I)

II. To evaluate the pathologic complete response rate (pCR) after combination of IFN-gamma with paclitaxel, trastuzumab and pertuzumab for 12 weeks of neoadjuvant therapy in patients with clinical stage 1-3 (primary tumor size >= 10 mm) HER2 positive breast cancer. (Phase II)

SECONDARY OBJECTIVES:

I. To evaluate overall response rate (OR, complete response [CR] + partial response [PR]) using standard response evaluation criteria in solid tumors (RECIST) version 1.1. (Phase I)

II. To evaluate median progression free survival (PFS). (Phase I)

III. To evaluate safety and tolerability of the combination therapy. (Phase II)

IV. To evaluate the PFS. (Phase II)

EXPLORATORY OBJECTIVES:

I. Determine whether IFN-gamma combination therapies restore anti-HER-2 CD4 Th1 response.

II. Determine whether IFN-gamma combination therapies change the tumor associated immune response.

III. Determine whether IFN-gamma combination therapies change the known tumor biomarkers that predict response in the HER-2 positive breast cancer.

OUTLINE: This is a phase I, dose-escalation study of interferon gamma-1b followed by a phase II study.

Patients receive interferon gamma-1b subcutaneously (SC) three times weekly for 12 weeks. Patients also receive paclitaxel intravenously (IV) over 60 minutes on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 79, and trastuzumab IV over 90 minutes and pertuzumab IV over 60 minutes on day 1. Cycles repeat every 21 days for 12 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for up to 2 years.

Trial Phase & Type

Trial Phase

Phase I/II

Trial Type

Treatment

Lead Organization

Lead Organization
Moffitt Cancer Center

Principal Investigator
Hyo Sook Han

Trial IDs

Primary ID MCC-18936
Secondary IDs NCI-2017-00923
Clinicaltrials.gov ID NCT03112590