HER2 irányított dendritesejtes vakcina a HER2+emlőrák neoadjuváns terápiája során
Kísérleti tanulmány HER2 irányított dendritesejtes vakcina alkalmazásával a HER2+ emlőrák neoadjuváns terápiája során
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.
A tanulmány áttekintése
Állapot
Körülmények
Beavatkozás / kezelés
Részletes leírás
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.
Tanulmány típusa
Beiratkozás (Tényleges)
Fázis
- 1. korai fázis
Kapcsolatok és helyek
Tanulmányi helyek
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Florida
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Tampa, Florida, Egyesült Államok, 33612
- H. Lee Moffitt Cancer Center and Research Institute
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Részvételi kritériumok
Jogosultsági kritériumok
Tanulmányozható életkorok
Egészséges önkénteseket fogad
Tanulmányozható nemek
Leírás
Inclusion Criteria:
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Participants must have histologically confirmed clinical stage II or III ERPR- HER2+ (per CAP criteria) invasive carcinoma of the breast
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Medically and surgically appropriate to undergo neoadjuvant chemotherapy with TCH-P Taxotere (docetaxel), Carboplatin, Herceptin (trastuzumab), Perjeta (pertuzumab) regimen followed by standard of care local therapy as determined by their treating physician
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Age ≥18 years.
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Eastern Cooperative Oncology Group (ECOG) performance status less than 2
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Patients must have normal organ and marrow function as defined below:
- leukocytes ≥3,000/μL
- absolute neutrophil count ≥1,500/μL
- platelets ≥100,000/μL
- total bilirubin within normal institutional limits
- AST(SGOT)/ALT(SGPT) less than or equal to 2.5 X institutional upper limit of normal
- creatinine within normal institutional limits - OR -
- creatinine clearance ≥60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
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Cardiac ejection fraction within institutional normal limits by either MUGA or ECHO at baseline.
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Women of child-bearing potential and their male partners must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Sexually active male participants should use a barrier method or exercise abstinence during chemotherapy administration until surgery.
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Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
- Patients with inflammatory breast cancer, widespread locally advanced unresectable disease involving the chest wall/nodal basins in which a curative surgical resection cannot be performed, or those in whom de novo metastatic disease is suspected or confirmed
- May not be receiving any other investigational agents for the treatment of their breast cancer.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to the study vaccine components and any of the chemotherapy drugs (docetaxel, carboplatin, trastuzumab, pertuzumab)
- Unwilling or unable to undergo an apheresis for production of their vaccine
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Women who are pregnant or breastfeeding
- Known congenital or acquired immune deficiency (including those patients who require systemic immunosuppressant drugs for autoimmune disease or organ transplant).
- Pre-existing peripheral neuropathy that would limit treatment with taxanes and platinum agents
Tanulási terv
Hogyan készül a tanulmány?
Tervezési részletek
- Elsődleges cél: Kezelés
- Kiosztás: Nem véletlenszerű
- Beavatkozó modell: Párhuzamos hozzárendelés
- Maszkolás: Nincs (Open Label)
Fegyverek és beavatkozások
Résztvevő csoport / kar |
Beavatkozás / kezelés |
|---|---|
|
Aktív összehasonlító: Lead In Phase - Arm A
Arm A: One Dendritic Cell Vaccine (DC1) per week x 3 weeks. |
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.
Más nevek:
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.
Más nevek:
Planned definitive curative surgery at 26 to 28 weeks. |
|
Aktív összehasonlító: Lead In Phase - Arm B
Arm B: Two DC1 vaccinations per week (given 3 days apart i.e., Mon and Thurs or Tues and Friday) x 3 weeks. |
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.
Más nevek:
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.
Más nevek:
Planned definitive curative surgery at 26 to 28 weeks. |
|
Kísérleti: Expansion Phase
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.
Más nevek:
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.
Más nevek:
Planned definitive curative surgery at 26 to 28 weeks. |
Mit mér a tanulmány?
Elsődleges eredményintézkedések
Eredménymérő |
Intézkedés leírása |
Időkeret |
|---|---|---|
|
Expansion Phase Schedule Selection by Week 4
Időkeret: By Week 4
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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). |
By Week 4
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Pathologic Complete Response (pCR) Rate
Időkeret: Week 26 to 28 - At post-surgical pathological assessment
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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). |
Week 26 to 28 - At post-surgical pathological assessment
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Másodlagos eredményintézkedések
Eredménymérő |
Intézkedés leírása |
Időkeret |
|---|---|---|
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Recurrence Free Survival (RFS)
Időkeret: Up to 3 years post-surgery
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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). |
Up to 3 years post-surgery
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Együttműködők és nyomozók
Együttműködők
Nyomozók
- Kutatásvezető: Haten Soliman, M.D., H. Lee Moffitt Cancer Center and Research Institute
Publikációk és hasznos linkek
Hasznos linkek
Tanulmányi rekorddátumok
Tanulmány főbb dátumok
Tanulmány kezdete (Tényleges)
Elsődleges befejezés (Tényleges)
A tanulmány befejezése (Tényleges)
Tanulmányi regisztráció dátumai
Először benyújtva
Először nyújtották be, amely megfelel a minőségbiztosítási kritériumoknak
Első közzététel (Tényleges)
Tanulmányi rekordok frissítései
Utolsó frissítés közzétéve (Tényleges)
Az utolsó frissítés elküldve, amely megfelel a minőségbiztosítási kritériumoknak
Utolsó ellenőrzés
Több információ
A tanulmányhoz kapcsolódó kifejezések
Kulcsszavak
További vonatkozó MeSH feltételek
Egyéb vizsgálati azonosító számok
- MCC-19337
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