Clinical Trials /

Phase I-II Study of Interferon-gamma in Patients With HER-2 Positive Breast Cancer

NCT03112590

Description:

This purpose of this study is to evaluate the safety and to find the optimal dose in participants with human epidermal growth factor receptor 2 (HER2) positive breast cancer who are given the combination of Interferon-gamma with paclitaxel, trastuzumab and pertuzumab. This study will also look at other effects of Interferon-gamma with paclitaxel, trastuzumab and pertuzumab, including its effect on this type of cancer. Interferon-gamma is a biologically manufactured protein that is similar to a protein the body makes naturally. In the body, interferon gamma is produced by immune cells and helps to prevent serious infections.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase I-II Study of Interferon-gamma in Patients With HER-2 Positive Breast Cancer
  • Official Title: A Phase I-II Study of Interferon-gamma Plus Weekly Paclitaxel, Trastuzumab and Pertuzumab in Patients With HER-2 Positive Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: MCC-18936
  • NCT ID: NCT03112590

Conditions

  • Breast Cancer
  • Breast Cancer, Male
  • Breast Cancer Female
  • HER2-positive Breast Cancer

Interventions

DrugSynonymsArms
PaclitaxelAbraxane®Combination Therapy
TrastuzumabHerceptin®Combination Therapy

Purpose

This purpose of this study is to evaluate the safety and to find the optimal dose in participants with human epidermal growth factor receptor 2 (HER2) positive breast cancer who are given the combination of Interferon-gamma with paclitaxel, trastuzumab and pertuzumab. This study will also look at other effects of Interferon-gamma with paclitaxel, trastuzumab and pertuzumab, including its effect on this type of cancer.

Interferon-gamma is a biologically manufactured protein that is similar to a protein the body makes naturally. In the body, interferon gamma is produced by immune cells and helps to prevent serious infections.

Detailed Description

Trial Arms

NameTypeDescriptionInterventions
Combination TherapyExperimentalPhase 1: Participants with HER-2 positive metastatic breast cancer enrolled in groups of 3-6 or more; each group participant to be given the same dose and schedule of Interferon-gamma plus paclitaxel, trastuzumab, and pertuzumab. If group participants do not have bad side effects, the next group will be given a higher dose of Interferon-gamma. This will continue until the highest safe dose of Interferon-gamma is found. Once highest safe dose of Interferon-gamma is found, participants may be enrolled in Phase II. Phase 2: Approximately 31 participants with Stage 2-3 HER2 positive early stage breast cancer enrolled to receive therapy with Interferon-gamma plus paclitaxel, trastuzumab, and pertuzumab. Interferon-gamma given at dose found in the Phase 1. Phase 2: Post therapy surgery.
    • Paclitaxel
    • Trastuzumab

    Eligibility Criteria

    Inclusion Criteria:

    - Participants must have a histologically confirmed HER2 positive breast cancer (by ImmunoHistoChemistry (IHC) 3+ or fluorescence in situ hybridization (FISH) ratio ≥ 2.0). Phase 1: unresectable locally advanced or metastatic breast cancer. Phase 2: clinical stage 2-3 early stage breast cancer.

    - Prior Therapy - Phase 1: Must be candidates to receive paclitaxel chemotherapy in combination with trastuzumab and pertuzumab. Phase 2: 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.

    - 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.

    - Age ≥ 18 years.

    - Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

    - Must have normal organ and marrow function within 2 weeks of registration (except where specified otherwise).

    - 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.

    - Ability to understand and willingness to sign a written informed consent document.

    Exclusion Criteria:

    - 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.

    - 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 participants with adrenal insufficiency are allowed).

    - 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 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.

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

    Primary Outcome Measures

    Measure:Phase 1: Recommended Phase 2 Dose (RP2D)
    Time Frame:12 weeks
    Safety Issue:
    Description:The dose limiting toxicity (DLT) evaluation period for dose escalation will be during the first three weeks. The maximum tolerated dose (MTD) dose level is defined as the highest dose level with ≤1 out of 6 participants experiencing a DLT. If the first dose level experience two or more DLTs, then dose de-escalation will occur. DLT during cycle one (C1) is defined as follows: Non-hematologic or hematologic toxicities that are ≥ grade 3 in severity and probably or definitely related to study therapy which leads to chemotherapy treatment delays > 14 days are considered DLT. The MTD will become the RP2D.

    Secondary Outcome Measures

    Measure:Phase 2: Clinical Response
    Time Frame:12 weeks
    Safety Issue:
    Description:Complete Response (CR) and Partial Response (PR) based upon tumor measurements obtained on physical examination at baseline, after completion of 4 cycles of study therapy. Factors that will be evaluated include: Breast mass(es) - size (longest dimension); Axillary lymph node(s) - size (longest dimension); Skin edema of the breast - present worse, present unchanged, present improved, or absent; Skin erythema of the breast - present worse, present unchanged, present improved, or absent.
    Measure:Phase 2: Progression Free Survival (PFS)
    Time Frame:Up to 2 years
    Safety Issue:
    Description:Progression will be evaluated in this study using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, version 1.1.

    Details

    Phase:Phase 1/Phase 2
    Primary Purpose:Interventional
    Overall Status:Not yet recruiting
    Lead Sponsor:H. Lee Moffitt Cancer Center and Research Institute

    Trial Keywords

    • Histologically confirmed HER2 positive breast cancer
    • Unresectable breast cancer
    • Locally advanced breast cancer
    • Metastatic breast cancer
    • Clinical stage 2-3 early stage breast cancer

    Last Updated

    April 10, 2017