Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Rare Diseases

Carcinoma

Breast Neoplasms

Breast Neoplasms, Male

Breast Diseases

Skin Diseases

Breast Cancer, Male

All Drugs and Chemicals

Vaccines

Immunologic Factors

Participants currently enrolled into arm A will offered randomization into arms C or D. If study participants decline randomization or are ineligible, they will complete study follow up visits as stated in the schedule of events per Arm A.

A history and physical exam will be taken at 3-month intervals. Any changes in history or physical condition will be documented. Patient currently enrolled into arm B will offered randomization into arms C or D once finished with arm B. If patients decline randomization or are ineligible, they will complete study follow up visits as stated in the schedule of events per Arm B.

A history and physical exam will be taken at 3-month intervals. Any changes in history or physical condition will be documented

A history and physical exam will be taken at 3-month intervals. Any changes in history or physical condition will be documented.

Ultrasound (US) guided intranodal delivered vaccines will be administered at each participating site by a radiologist experienced in ultrasound guided procedures along with the principal investigator or his/her designee. Each dose will consist of between 1.0-2.0 x 10\^7 cells and will be injected into 1 right and 1 left normal groin lymph nodes.

HER2 DC1 Vaccine

Ricardo Costa, M.D.

The purpose of this study is to learn more about how to treat patients with a diagnosis of diagnosis of Human Epidermal Growth Factor Receptor 2/neu (HER-2/neu) positive breast cancer in the past, who were previously treated with HER-2/neu-directed dendritic cells (DC) vaccines.

There is evidence that the use of anti-HER2 dendritic cell (DC) study vaccines could improve response to breast cancer therapy and be an important step in the prevention of recurrence.

This study will use a Dendritic Cell Type 1 (DC1) vaccine which is a HER2-sensitized dendritic cell (DC) study vaccine. Dendritic cells are immune cells that can tell the participant's immune system to fight infection. This study vaccine will be made from the participant's blood cells collected from a procedure called leukapheresis.

Immune Response and Potential Booster for Patients Who Have Received HER2-pulsed DC1

Immune Response Surveillance and Potential Booster Vaccines for Patients Who Have Received HER2-pulsed DC1 Vaccine

Investigators will assess the feasibility of participants receiving the six-booster regimen if 11/15 randomized to Arm D complete all 6 booster injections.

To compare the overall average effects of two different vaccine regimens on anti-HER2 CD4 immunity (ELISPOT) at 18 months from month 1 injection. treatment among women with breast cancer previously treated with HER2 vaccines. Two regimens consist of 3 versus 6 booster HER2 vaccine injections administered every 3 months

To compare the overall average effects of two different vaccine regimens on anti-HER2 CD4 immunity (ELISPOT) at month 10 from first vaccine treatment

Serious adverse events will be recorded for 100 days after study treatment. Adverse events will follow National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

OS will be measured using the Kaplan-Meier method

DFS will be measured using the Kaplan-Meier method

PFS will be measured using the Kaplan-Meier method

H. Lee Moffitt Cancer Center and Research Institute

Heart and Blood Diseases

Symptoms and General Pathology

Substance Related Disorders

Wounds and Injuries

Cardiotoxicity

Fluorodeoxyglucose F18

Radiopharmaceuticals

Study agent: 2-deoxy-2-\[18F\]fluoro-D-glucose (FDG). Fluoro-D-glucose-positron Emission Tomography: Participants will undergo a PET-CT scan with Fluoro-D-glucose-labeled (FDG-labeled) red blood cells (RBCs) within 2 weeks of obtaining an echocardiogram prior to start of chemotherapy. A repeat FDG-RBC PET-CT scan will be completed within two weeks of obtaining their follow-up echocardiogram to determine post-therapy cardiac ejection fraction. If the participant has an echocardiogram obtained prior to completion of chemotherapy, an attempt will be made to obtain a FDG-RBC PET-CT scan within two weeks of the echocardiogram.

2-deoxy-2-\[18F\]Fluoro-D-glucose-positron Emission Tomography (FDG-PET): within 2 weeks of obtaining first echocardiogram; within two weeks of obtaining follow-up echocardiogram.

Fluoro-D-glucose-positron Emission Tomography

2-deoxy-2-\[18F\]fluoro-D-glucose (FDG) labeled autologous human erythrocytes (RBCs): Approximately 10 mls of packed human erythrocytes are collected from the patient and labeled with ≈5-10 milliCuries of commercially available United States Pharmacopeia (USP)-grade FDG (≈5-10 picograms FDG) (Vendor: Cardinal Health) under sterile conditions in a Good Manufacturing Practice (GMP)-certified laboratory.

Synthesized RBCs: The cell suspension is manually infused via syringe through an indwelling peripheral venous catheter over the course of 1 minute, using an infusion method approved by the Moffitt Cancer Center (MCC) radiation safety officer.

2-deoxy-2-[18F]fluoro-D-glucose (FDG)

Echocardiogram: prior to start of chemotherapy; post-treatment regimen.

Echocardiogram

Jung Choi, M.D.

This is a single arm, phase 0 study to evaluate the safety and efficacy of PET-CT scans with FDG-labeled RBC in patients with breast cancer.

Cardiac ejection fraction can be calculated and monitored in breast cancer patients during chemotherapy using a FDG-RBC PET-CT scan. The purpose of this study is to determine if calculated cardiac ejection fraction shows high concordance with results from echocardiography.

PET-CT Imaging Using FDG-labeled Human Erythrocytes in Breast Cancer Patient

Pilot Study of PET-CT Imaging Using FDG-labeled Human Erythrocytes in Breast Cancer Patient Before and After Neoadjuvant Chemotherapy

Calculated cardiac ejection fraction (EF) with a low radiation dose FDG-RBC PET-computed tomography (CT) scan before and after neoadjuvant chemotherapy.

The concordance will be estimated by the use of Lin's method49 along with 95% confidence interval.

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

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).

Phase 2: Pathologic Complete Response Rate (pCR)

Complete Response

Partial Response

Stable Disease

Progressive Disease

Phase 2: Clinical Response

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

Overall Study

Docetaxel

Carboplatin

Immunomodulating Agents

Arm A: One Dendritic Cell Vaccine (DC1) per week x 3 weeks.

Arm B: Two DC1 vaccinations per week (given 3 days apart i.e., Mon and Thurs or Tues and Friday) x 3 weeks.

DC1 vaccinations according to optimal vaccination schedule. Participants will receive a booster intranodal study vaccine at week 25 prior to receiving surgery. Participants will then undergo definitive curative surgery following completion of the neoadjuvant therapy, additional adjuvant locoregional/systemic therapy (as deemed appropriate by their treating physicians).

Study Vaccine:

Lead In Phase - Weekly as outlined in each treatment Arm.

Expansion Phase - At the optimal schedule determined at the end of the Lead In Phase.

Pre-surgery - Booster Vaccine at week 25 prior to receiving surgery.

Post-surgery - Participants will receive a series of 3 booster intranodal study vaccines given once every 6 months.

Dendritic Cell Vaccine (DC1)

Upon completion of the 3 week series of vaccinations participants will then undergo neoadjuvant chemotherapy treatment with the TCH-P Taxotere (docetaxel), Carboplatin, Herceptin (trastuzumab), Perjeta (pertuzumab) standard of care neoadjuvant chemotherapy regimen given intravenously once every 3 weeks for up to 6 cycles. The treating physician will have the discretion to delay, modify, or shorten the neoadjuvant chemotherapy as per routine practice guidelines and physician discretion.

Neoadjuvant Chemotherapy

Planned definitive curative surgery at 26 to 28 weeks.

Curative Surgery

Haten Soliman, M.D.

The purpose of this study is to learn more about how to treat patients with HER-2/neu positive invasive breast cancer (IBC). HER-2/neu is a type of protein that is known to be over-expressed in aggressive breast cancer.

The study drug for this trial is DC1 study vaccine which is a HER2-sensitized dendritic cell (DC) study vaccine. This study vaccine is made from the participant's blood cells collected from a procedure called leukapheresis. Dendritic cells are immune cells that can tell the immune system to fight infection. In laboratory testing and from previous studies in participants, these cells may also help the immune system attack tumors such as breast cancer.

The trial will consist of two phases. The first lead in phase will enroll 12 participants evenly divided into two arms (alternating enrollment) with different initial priming study vaccination schedules.

Arm A: One DC1 study vaccination per week x 3 weeks. Arm B: Two DC1 study vaccinations per week (given 3 days apart for example Mon and Thurs or Tues and Friday) x 3 weeks.

Following accrual of this initial group of 12 participants, HER2 ELISPOT post study vaccination responses will be assessed to determine which of the two sequences provides the greater increase in anti HER2 response at week 4 over baseline. This will determine which sequence will be used in the second expansion phase of accrual. If both arms are determined equal then Arm A will be selected as the default sequence.

Second phase of accrual will consist of 14 additional participants to undergo study vaccination using the optimal schedule declared in the first phase of the trial. The trial will consist of two phases. The first lead in phase will enroll 12 participants evenly divided into two arms (alternating enrollment) with different initial priming study vaccination schedules.

Arm A: One DC1 study vaccination per week x 3 weeks Arm B: Two DC1 study vaccinations per week (given 3 days apart for example Mon and Thurs or Tues and Friday) x 3 weeks.

Following accrual of this initial group of 12 participants, HER2 ELISPOT post study vaccination responses will be assessed to determine which of the two sequences provides the greater increase in anti HER2 response at week 4 over baseline. This will determine which sequence will be used in the second expansion phase of accrual. If both arms are determined equal then Arm A will be selected as the default sequence.

Second phase of accrual will consist of 14 additional participants to undergo study vaccination using the optimal schedule declared in the first phase of the trial.

The trial will consist of two phases. The first lead in phase will enroll 12 participants evenly divided into two arms (alternating enrollment) with different initial priming vaccination schedules.

Following accrual of this initial group of 12 patients, HER2 ELISPOT post vaccination responses will be assessed to determine which of the two sequences provides the greater increase in anti HER2 response at week 4 over baseline. This will determine which sequence will be used in the second expansion phase of accrual. If both arms are determined equal then Arm A will be selected as the default sequence.

HER2 Directed Dendritic Cell Vaccine During Neoadjuvant Therapy of HER2+Breast Cancer

A Pilot Study Utilizing a HER2 Directed Dendritic Cell Vaccine During Neoadjuvant Therapy of HER2+ Breast Cancer

Immunogenicity of HER2 DC Vaccine per treatment Arm, based on week 4 ELISPOTs. Three metrics of CD4+ Th1 response will be computed for each patient, (a) overall anti-HER2 responsivity (i.e., if patient demonstrates a positive ELISPOT response to \>1 peptide, (b) response repertoire (i.e., number of reactive peptides) and (c) cumulative response (total SFC/10\^6 cells across 6 peptides). The primary immunogenicity outcome will be the cumulative response at week 4 (week after completion of all vaccinations).

Pathologic complete response rate of participants treated in the Expansion Phase. Clinical efficacy will be defined by the pathologic complete response (pCR) rate, the percentage of patients who achieve pCR based on surgical pathology assessment.The definition of pathologic complete response (pCR) will be ypT0/is N0 (no residual viable invasive disease in the breast or nodes). Any response less than pCR will be scored as incomplete response or progression (if tumor size increases during neoadjuvant chemotherapy on physical exam/breast imaging).

Recurrence-free survival (RFS) will be defined as the time from first vaccination to documented recurrence (any breast event), death due to any cause or last patient contact that documents recurrence-free status (i.e., a clinic or scan date).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Immune Response and Potential Booster for Patients Who Have Received HER2-pulsed DC1	NCT03630809	Breast Cancer HER2-positive B... HER-2 Gene Ampl... HER2 Positive B... HER-2 Protein O... Breast Cancer, ... Breast Cancer F...	HER2 DC1 Vaccin...	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
PET-CT Imaging Using FDG-labeled Human Erythrocytes in Breast Cancer Patient	NCT03295695	Breast Cancer Breast Cancer, ... Breast Cancer, ... Breast Neoplasm...	Fluoro-D-glucos... 2-deoxy-2-[18F]... Echocardiogram	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
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
HER2 Directed Dendritic Cell Vaccine During Neoadjuvant Therapy of HER2+Breast Cancer	NCT03387553	Breast Cancer Breast Cancer F... Breast Cancer, ... Invasive Breast... HER2-positive B... HER2 Positive B... Stage II Breast... Stage III Breas...	Dendritic Cell ... Neoadjuvant Che... Curative Surger...	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
PET-CT Imaging Using FDG-labeled Human Erythrocytes in Breast Cancer Patient	NCT03295695	Breast Cancer Breast Cancer, ... Breast Cancer, ... Breast Neoplasm...	Fluoro-D-glucos... 2-deoxy-2-[18F]... Echocardiogram	18 Years -	H. Lee Moffitt Cancer Center and Research Institute

Spots Global Cancer Trial Database for breast cancer, male