Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Breast Neoplasms

Breast Neoplasms, Male

Breast Diseases

Skin Diseases

Breast Cancer, Male

All Drugs and Chemicals

Antineoplastic Agents

Anti-Infective Agents

Antibodies

Antibodies, Monoclonal

Paclitaxel

Trastuzumab

Albumin-Bound Paclitaxel

Immunoglobulins

Interferons

Pertuzumab

Interferon-gamma

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Antiviral Agents

Phase 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.

Phase 1: IFN-γ 50 or 75 mcg/m\^2 SQ x 3 days/week for 12 weeks. Phase 2: IFN-γ at Recommended Phase II Dose (RP2D) subcutaneously (SQ) x 3 days/week, for 12 weeks.

Interferon-gamma (IFN-γ)

Phase 1 and Phase 2: Paclitaxel 80 mg/m\^2/week, for 12 weeks.

Phase 1 and Phase 2: Trastuzumab 8 mg/kg intravenous (IV) loading dose on cycle 1/day 1 (C1D1), followed by 6 mg/kg on subsequent cycles every 3 weeks, for 12 weeks.

Phase 1 and Phase 2: Pertuzumab 840 mg IV loading dose on C1D1, followed by 420 mg on subsequent cycles every 3 weeks, for 12 weeks.

Phase 2: Participants will be assessed for surgery following the fourth cycle of study therapy (or earlier if study treatment is cancelled due to unmanageable side effects).

Post Therapy Surgery

(Hyo) Heather S. Han, M.D.

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.

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

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

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.

Pathologic complete response in the breast at definitive surgery after completion of protocol therapy. The pathologic response to treatment will be assessed by an institutional pathologist at Moffitt Cancer Center. The pathologist will evaluate response by the "Residual Cancer Burden"(RCB) for each participant as described in the online calculator (see RCB link in the More Information section). pCR is defined as no residual invasive carcinoma in the breast and lymph notes at definitive surgery following neoadjuvant therapy

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.

Progression will be evaluated in this study using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, version 1.1.

PFS is defined as the time from study therapy to the first occurrence of ipsilateral invasive breast tumor recurrence, ipsilateral locoregional invasive breast cancer recurrence, contralateral invasive breast cancer, distant recurrence, or death from any cause. This is reported as number of participants who progressed.

Horizon Pharma Ireland, Ltd., Dublin Ireland

H. Lee Moffitt Cancer Center and Research Institute

Interferon-gamma (IFN-γ): Phase 1: IFN-γ 50 mcg/m\^2 SQ x 3 days/week for 12 weeks.

Paclitaxel: Phase 1 and Phase 2: Paclitaxel 80 mg/m\^2/week, for 12 weeks.

Trastuzumab: Phase 1 and Phase 2: Trastuzumab 8 mg/kg intravenous (IV) loading dose on cycle 1/day 1 (C1D1), followed by 6 mg/kg on subsequent cycles every 3 weeks, for 12 weeks.

Pertuzumab: Phase 1 and Phase 2: Pertuzumab 840 mg IV loading dose on C1D1, followed by 420 mg on subsequent cycles every 3 weeks, for 12 weeks.

Phase 1 Level 1

Interferon-gamma (IFN-γ): Phase 1: IFN-γ 75 mcg/m\^2 SQ x 3 days/week for 12 weeks.

Paclitaxel: Phase 1 and Phase 2: Paclitaxel 80 mg/m\^2/week, for 12 weeks.

Trastuzumab: Phase 1 and Phase 2: Trastuzumab 8 mg/kg intravenous (IV) loading dose on cycle 1/day 1 (C1D1), followed by 6 mg/kg on subsequent cycles every 3 weeks, for 12 weeks.

Pertuzumab: Phase 1 and Phase 2: Pertuzumab 840 mg IV loading dose on C1D1, followed by 420 mg on subsequent cycles every 3 weeks, for 12 weeks.

Phase 1 Level 2

Interferon-gamma (IFN-γ): Phase 2: IFN-γ 75 mcg/m\^2 SQ x 3 days/week for 12 weeks.

Paclitaxel: Phase 1 and Phase 2: Paclitaxel 80 mg/m\^2/week, for 12 weeks.

Trastuzumab: Phase 1 and Phase 2: Trastuzumab 8 mg/kg intravenous (IV) loading dose on cycle 1/day 1 (C1D1), followed by 6 mg/kg on subsequent cycles every 3 weeks, for 12 weeks.

Pertuzumab: Phase 1 and Phase 2: Pertuzumab 840 mg IV loading dose on C1D1, followed by 420 mg on subsequent cycles every 3 weeks, for 12 weeks.

Phase 2

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Hyo S. Han, MD

Interferon-gamma (IFN-γ): Phase 1: IFN-γ 50 or 75 mcg/m\^2 SQ x 3 days/week for 12 weeks.

Phase 2: IFN-γ at Recommended Phase II Dose (RP2D) subcutaneously (SQ) x 3 days/week, for 12 weeks.

Paclitaxel: Phase 1 and Phase 2: Paclitaxel 80 mg/m\^2/week, for 12 weeks.

Trastuzumab: Phase 1 and Phase 2: Trastuzumab 8 mg/kg intravenous (IV) loading dose on cycle 1/day 1 (C1D1), followed by 6 mg/kg on subsequent cycles every 3 weeks, for 12 weeks.

Pertuzumab: Phase 1 and Phase 2: Pertuzumab 840 mg IV loading dose on C1D1, followed by 420 mg on subsequent cycles every 3 weeks, for 12 weeks.

Combination Therapy

Phase 1: Recommended Phase 2 Dose (RP2D)

Paclitaxel: Phase 1 and Phase 2: Paclitaxel 80 mg/m\^2/week, for 12 weeks.

Trastuzumab: Phase 1 and Phase 2: Trastuzumab 8 mg/kg intravenous (IV) loading dose on cycle 1/day 1 (C1D1), followed by 6 mg/kg on subsequent cycles every 3 weeks, for 12 weeks.

Pertuzumab: Phase 1 and Phase 2: Pertuzumab 840 mg IV loading dose on C1D1, followed by 420 mg on subsequent cycles every 3 weeks, for 12 weeks.

Post Therapy Surgery: Phase 2: Participants will be assessed for surgery following the fourth cycle of study therapy (or earlier if study treatment is cancelled due to unmanageable side effects).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Phase I-II Study of Interferon-gamma in Patients With HER-2 Positive Breast Cancer	NCT03112590	Breast Cancer Breast Cancer, ... Breast Cancer F... HER2-positive B...	Interferon-gamm... Paclitaxel Trastuzumab Pertuzumab Post Therapy Su...	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
Phase I-II Study of Interferon-gamma in Patients With HER-2 Positive Breast Cancer	NCT03112590	Breast Cancer Breast Cancer, ... Breast Cancer F... HER2-positive B...	Interferon-gamm... Paclitaxel Trastuzumab Pertuzumab Post Therapy Su...	18 Years -	H. Lee Moffitt Cancer Center and Research Institute

Spots Global Cancer Trial Database for histologically confirmed her2 positive breast cancer