Phase I-II Study of Interferon-gamma in Patients With HER-2 Positive Breast Cancer
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|ClinicalTrials.gov Identifier: NCT03112590|
Recruitment Status : Active, not recruiting
First Posted : April 13, 2017
Results First Posted : June 8, 2022
Last Update Posted : July 19, 2022
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.
|Condition or disease||Intervention/treatment||Phase|
|Breast Cancer Breast Cancer, Male Breast Cancer Female HER2-positive Breast Cancer||Biological: Interferon-gamma (IFN-γ) Drug: Paclitaxel Drug: Trastuzumab Other: Pertuzumab Procedure: Post Therapy Surgery||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||51 participants|
|Intervention Model:||Sequential Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I-II Study of Interferon-gamma Plus Weekly Paclitaxel, Trastuzumab and Pertuzumab in Patients With HER-2 Positive Breast Cancer|
|Actual Study Start Date :||June 23, 2017|
|Actual Primary Completion Date :||March 31, 2021|
|Estimated Study Completion Date :||June 2023|
Experimental: Combination Therapy
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)
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.
Phase 1 and Phase 2: Paclitaxel 80 mg/m^2/week, for 12 weeks.
Other Name: Abraxane®
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.
Other Name: Herceptin®
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.
Procedure: 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).
- Phase 1: Recommended Phase 2 Dose (RP2D) [ Time Frame: 12 weeks ]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.
- Phase 2: Pathologic Complete Response Rate (pCR) [ Time Frame: After post therapy surgery - Therapy: approximately 12 weeks per participant ]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
- Phase 2: Clinical Response [ Time Frame: 12 weeks ]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.
- Phase 2: Progression Free Survival (PFS)/Number of Participants Who Progressed [ Time Frame: Up to 2 years ]
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03112590
|United States, Florida|
|H. Lee Moffitt Cancer Center and Research Institute|
|Tampa, Florida, United States, 33612|
|Principal Investigator:||(Hyo) Heather S. Han, M.D.||H. Lee Moffitt Cancer Center and Research Institute|