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

NCT03112590 | Completed Phase 1 Results FDA Drug

• 1 other identifier: MCC-18936
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

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

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

Outcome Measures

Primary Outcomes (2)

• Phase 1: Recommended Phase 2 Dose (RP2D)

  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.

  12 weeks

• Phase 2: Pathologic Complete Response Rate (pCR)

  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

  After post therapy surgery - Therapy: approximately 12 weeks per participant

Secondary Outcomes (2)

• Phase 2: Clinical Response

  12 weeks

• Phase 2: Progression Free Survival (PFS)/Number of Participants Who Progressed

  Up to 2 years

Study Arms (1)

Combination Therapy

EXPERIMENTAL

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.

Biological: Interferon-gamma (IFN-γ); Drug: Paclitaxel; Drug: Trastuzumab; Other: Pertuzumab; Procedure: Post Therapy Surgery

Interventions

Interferon-gamma (IFN-γ) BIOLOGICAL

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.

Also known as: Actimmune®, signaling proteins

Combination Therapy

Paclitaxel DRUG

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

Also known as: Abraxane®

Combination Therapy

Trastuzumab DRUG

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.

Also known as: Herceptin®

Combination Therapy

Pertuzumab OTHER

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.

Also known as: PERJETA®, monoclonal antibody

Combination Therapy

Post Therapy Surgery PROCEDURE

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).

Combination Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 1-3 early stage breast cancer with primary tumor is at least 1cm measured by clinical exam or by radiologic breast imaging tests.
• 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 equal to or less than 1 cycle of therapy (up to 4 weeks) will be allowed to enroll in 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Horizon Pharma Ireland, Ltd., Dublin Ireland: collaborator

Study Sites (1)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Related Publications (1)

• Gautam N, Elleson KM, Ramamoorthi G, Czerniecki BJ. Current State of Cell Therapies for Breast Cancer. Cancer J. 2022 Jul-Aug 01;28(4):301-309. doi: 10.1097/PPO.0000000000000607.

  PMID: 35880940 DERIVED

Related Links

• Moffitt Cancer Center Clinical Trials website
• Residual Cancer Burden (RCB)

MeSH Terms

Conditions

Breast Neoplasms; Breast Neoplasms, Male

Interventions

Interferon-gamma; interferon gamma-1b; Paclitaxel; Albumin-Bound Paclitaxel; Trastuzumab; pertuzumab; Antibodies, Monoclonal

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Macrophage-Activating Factors; Lymphokines; Proteins; Biological Factors; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Antibodies, Monoclonal, Humanized; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Hyo S. Han, MD
• Organization: Moffitt Cancer Center

Hyo.Han@moffitt.org

813-745-4933

Study Officials

• (Hyo) Heather S. Han, M.D.

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2017
• First Posted: April 13, 2017
• Study Start: June 23, 2017
• Primary Completion: March 31, 2021
• Study Completion: February 20, 2023
• Last Updated: April 19, 2023
• Results First Posted: June 8, 2022

Record last verified: 2023-04

Locations

US (1)