Vaccination of High Risk Breast Cancer Patients | NCT02229084

NCT02229084

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Part 1 - Chemovax Schedule A	Experimental	Feasibility - Chemovax schedule A: Subjects will receive the first cycle of chemotherapy along with the first injection of P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine on week 1, the subsequent two injections of the vaccine one week apart (week 2 and 3), second cycle of chemotherapy on week 4, and subsequent cycles of chemotherapy every 21 days (week 7,10,13,16,19,22).	Biological: P10s-PADRE/ MONTANIDE™ ISA 51 VG Drug: Doxorubicin Drug: Cyclophosphamide Drug: Docetaxel
Part 1 - Chemovax Schedule B	Experimental	Feasibility - Chemovax Schedule B: Subjects will receive the first cycle of chemotherapy on week 1, the first injection of P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine on week 2, the subsequent two injections of the vaccine one week apart (week 3 and 4), second cycle of chemotherapy on week 4 (along with second vaccine injection) and subsequent cycles of chemotherapy every 21 days (week 7,10,13,16,19,22).	Biological: P10s-PADRE/ MONTANIDE™ ISA 51 VG Drug: Doxorubicin Drug: Cyclophosphamide Drug: Docetaxel
Part 1 - Chemovax Schedule C	Experimental	Feasibility - Chemovax Schedule C: Subjects will receive three weekly injections of P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine (week 1,2,3), then first cycle of chemotherapy (week 4), and subsequent cycles of chemotherapy every 21 days (week 7,10,13,16,19,22,25).	Biological: P10s-PADRE/ MONTANIDE™ ISA 51 VG Drug: Doxorubicin Drug: Cyclophosphamide Drug: Docetaxel
Part 1 - Chemovax Schedule D

Interventions

Name	Type	Description	Arm Group Labels	Other Names
P10s-PADRE/ MONTANIDE™ ISA 51 VG	Biological	Eligible subjects will be enrolled and immunized by SC administration of P10s-PADRE vaccine on each of 3 separate occasions concurrent with chemotherapy.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Identify a Feasible Schedule of Vaccination Relative to SoC Neoadjuvant Chemotherapy When the Chemovax Are Administered Concurrently.	Number of participants with sufficiently high anti-P10s immunoglobulin-G response Feasibility will be evaluated in terms of Generation of a sufficiently high anti-P10s immunoglobulin-G response Safety and tolerability of the combination of vaccine and chemotherapy	At the time of definitive surgery (4-8 weeks after chemo, which is between Week 22 and Week 25)
Determine the pCR Rate	The patient-level primary outcome for this objective is pathological Complete Response (pCR), which is binary yes/no, and the study-level endpoint for this outcome is the rate of pCR, i.e. the percentage of patients that achieved pCR=yes. The patient is assessed at the time of surgery for whether they achieved pCR=yes. They have to do the surgery in order to obtain the tissue samples on which they do their pCR assessment. Pathological Complete Response is defined as the absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes following completion of neoadjuvant systemic therapy (i.e., ypT0N0 or ypTisN0 in the AJCC staging system for staging solid tumors in the neoadjuvant setting that was described in a 2014 FDA Guidance for Industry).	At the time of definitive surgery (4-8 weeks after chemo, which is between Week 22 and Week 25)

Secondary Outcomes

Measure	Description	Time Frame
P10s-MAP-Reactive Immunoglobulin Titers	The anti-P10s binding level was measured via ELISA method after incubation with a subject's serum or plasma sample. Data was collected at multiple timepoints throughout the study. Values were averaged for each group.	Week 1 through Week 70
Activation Profiles of NK Cells: Pre-Immune and Post-Immune CD16

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Females of all races with clinical stage I, II, or III ER-positive, HER2 negative breast cancer who will undergo SoC neoadjuvant treatment.
Age 18 years and older.
ECOG Performance Status 0 or 1.
White blood cell (WBC) count ≥ 3,000/mm3 within 3 weeks prior to registration.
Platelet count ≥ 100,000/mm3 within 3 weeks prior to registration.
Bilirubin ≤ 2 x institutional upper limit (IUL) of normal obtained within 3 weeks prior to registration.
Serum glutamic-oxaloacetic transaminase (SGOT) or aspartate aminotransferase test (AST) ≤ 2 x IUL of normal obtained within 3 weeks prior to registration.
Serum glutamic-pyruvic transaminase (SGPT) or alanine aminotransferase test (ALT) ≤ 2 x IUL of normal obtained within 3 weeks prior to registration.
Serum creatinine ≤ 1.8 mg/dL obtained within 3 weeks prior to registration.
Must sign an informed consent document approved by the UAMS IRB.

Exclusion Criteria:

ER-negative, HER2-positive, inflammatory, metastatic, stage IV or recurrent breast cancer
Active infection requiring treatment with antibiotics.
Existing diagnosis or history of organic brain syndrome that might preclude participation in the full protocol.
Existing diagnosis or history of significant impairment of basal cognitive function that might preclude participation in the full protocol.
Other current malignancies. Subjects with prior history at any time of any in situ cancer, including lobular carcinoma of the breast in situ, cervical cancer in situ, atypical melanocytic hyperplasia or Clark I melanoma in situ or basal or squamous skin cancer are eligible, provided they are disease-free at the time of registration. Subjects with other malignancies are eligible if they have been continuously disease free for ≥ 5 years prior to the time of registration.
Active autoimmune disorders or conditions of immunosuppression; Existing diagnosis or history of autoimmune disorders or conditions of immunosuppression that have been in remission for less than 6 months
Treatment with corticosteroids, including oral steroids (i.e. prednisone, dexamethasone [except when used as an antiemetic in SoC therapy]), continuous use of topical steroid creams or ointments or any steroid-containing inhalers. Subjects who discontinue the use of these classes of medication for at least 6 weeks prior to registration are eligible if, in the judgment of the treating physician, the subject is not likely to require these classes of drugs during the treatment period. Replacement doses of steroids for subjects with adrenal insufficiency are allowed.
Pregnancy or breastfeeding (due to the unknown effects of peptide/mimotope vaccines on a fetus or infant). Women of childbearing potential must have a negative urine pregnancy test within 72 hours prior to starting week 1 and must be counseled to use an accepted and effective method of contraception (including abstinence) while on treatment and for a period of 18 months after completing or discontinuing treatment. Accepted methods of contraception include tubal ligation, oral contraceptives, barrier methods, IUDs, and abstinence.
Any other significant medical or psychiatric conditions, which, in the opinion of the enrolling investigator, may interfere with consent or compliance of the treatment regimen.
Enrollment in any other clinical trial using investigational drug products or devices prior to first post-surgery study lab. Concurrent enrollment in observational studies is allowed.

Name	Affiliation	Role
Sri Obulareddy, MD	University of Arkansas	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Highlands Oncology Group		Fayetteville	Arkansas	72703	United States
University of Arkansas for Medical Sciences

PubMed Identifier	Type	Citation	Retractions
32582547	Derived	Hernandez Puente CV, Hsu PC, Rogers LJ, Jousheghany F, Siegel E, Kadlubar SA, Beck JT, Makhoul I, Hutchins LF, Kieber-Emmons T, Monzavi-Karbassi B. Association of DNA-Methylation Profiles With Immune Responses Elicited in Breast Cancer Patients Immunized With a Carbohydrate-Mimicking Peptide: A Pilot Study. Front Oncol. 2020 Jun 5;10:879. doi: 10.3389/fonc.2020.00879. eCollection 2020.

Arm/Group Information

ID	Title	Description
FG000	Part 1 - Chemovax Schedule A	Feasibility - Chemovax schedule A: Subjects will receive the first cycle of chemotherapy along with the first injection of P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine on week 1, the subsequent two injections of the vaccine one week apart (week 2 and 3), second cycle of chemotherapy on week 4, and subsequent cycles of chemotherapy every 21 days (week 7,10,13,16,19,22). Chemovax - P10s-PADRE/ MONTANIDE™ ISA 51 VG + Doxorubicin + Cyclophosphamide + Docetaxel (or Paclitaxel): Eligible subjects will be enrolled and immunized by SC administration of P10s-PADRE vaccine on each of 3 separate occasions over a three-week period.
FG001	Part 1 - Chemovax Schedule B	Feasibility - Chemovax Schedule B: Subjects will receive the first cycle of chemotherapy on week 1, the first injection of P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine on week 2, the subsequent two injections of the vaccine one week apart (week 3 and 4), second cycle of chemotherapy on week 4 (along with second vaccine injection) and subsequent cycles of chemotherapy every 21 days (week 7,10,13,16,19,22). Chemovax - P10s-PADRE/ MONTANIDE™ ISA 51 VG + Doxorubicin + Cyclophosphamide + Docetaxel (or Paclitaxel): Eligible subjects will be enrolled and immunized by SC administration of P10s-PADRE vaccine on each of 3 separate occasions over a three-week period.
FG002	Part 1 - Chemovax Schedule C	Feasibility - Chemovax Schedule C: Subjects will receive three weekly injections of P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine (week 1,2,3), then first cycle of chemotherapy (week 4), and subsequent cycles of chemotherapy every 21 days (week 7,10,13,16,19,22,25). Chemovax - P10s-PADRE/ MONTANIDE™ ISA 51 VG + Doxorubicin + Cyclophosphamide + Docetaxel (or Paclitaxel): Eligible subjects will be enrolled and immunized by SC administration of P10s-PADRE vaccine on each of 3 separate occasions over a three-week period.
FG003	Part 1 - Chemovax Schedule D	Feasibility - Chemovax Schedule D: Subjects will receive the first injection of vaccine on week 1, the subsequent two injections of the P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine one week apart (week 2 and 3), the first cycle of chemotherapy on week 2 (along with second vaccine injection) and subsequent cycles of chemotherapy every 21 days (week 5,8,11,14,17,20,23). Chemovax - P10s-PADRE/ MONTANIDE™ ISA 51 VG + Doxorubicin + Cyclophosphamide + Docetaxel (or Paclitaxel): Eligible subjects will be enrolled and immunized by SC administration of P10s-PADRE vaccine on each of 3 separate occasions over a three-week period.
FG004	Part 1 - Chemovax Schedule E	Feasibility - Chemovax Schedule E: Subjects will receive the first injection of vaccine on week 1, the subsequent two injections of the P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine one week apart (week 2 and 3), the first cycle of chemotherapy on week 3 (along with third vaccine injection) and subsequent cycles of chemotherapy every 21 days (week 6,9,12,15,18,21,24). Chemovax - P10s-PADRE/ MONTANIDE™ ISA 51 VG + Doxorubicin + Cyclophosphamide + Docetaxel (or Paclitaxel): Eligible subjects will be enrolled and immunized by SC administration of P10s-PADRE vaccine on each of 3 separate occasions over a three-week period.
FG005	Part 2 - Chemovax Schedule C	Primary Efficacy - Chemovax Schedule C: Subjects will receive three weekly injections of P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine (week 1,2,3), then first cycle of chemotherapy (week 4), and subsequent cycles of chemotherapy every 21 days (week 7,10,13,16,19,22,25). Chemovax - P10s-PADRE/ MONTANIDE™ ISA 51 VG + Doxorubicin + Cyclophosphamide + Docetaxel (or Paclitaxel): Eligible subjects will be enrolled and immunized by SC administration of P10s-PADRE vaccine on each of 3 separate occasions over a three-week period.
FG006	Part 3 - Chemovax Schedule C	Expanded Efficacy - Chemovax Schedule C: Subjects will receive three weekly injections of P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine (week 1,2,3), then first cycle of chemotherapy (week 4), and subsequent cycles of chemotherapy every 21 days (week 7,10,13,16,19,22,25 Chemovax - P10s-PADRE/ MONTANIDE™ ISA 51 VG + Doxorubicin + Cyclophosphamide + Docetaxel (or Paclitaxel): Eligible subjects will be enrolled and immunized by SC administration of P10s-PADRE vaccine on each of 3 separate occasions over a three-week period.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Part 1 - Chemovax Schedule A	Feasibility - Chemovax schedule A: Subjects will receive the first cycle of chemotherapy along with the first injection of P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine on week 1, the subsequent two injections of the vaccine one week apart (week 2 and 3), second cycle of chemotherapy on week 4, and subsequent cycles of chemotherapy every 21 days (week 7,10,13,16,19,22). Chemovax - P10s-PADRE/ MONTANIDE™ ISA 51 VG + Doxorubicin + Cyclophosphamide + Docetaxel (or Paclitaxel): Eligible subjects will be enrolled and immunized by SC administration of P10s-PADRE vaccine on each of 3 separate occasions over a three-week period.

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Categorical			Count of Participants

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Identify a Feasible Schedule of Vaccination Relative to SoC Neoadjuvant Chemotherapy When the Chemovax Are Administered Concurrently.

Number of participants with sufficiently high anti-P10s immunoglobulin-G response Feasibility will be evaluated in terms of

Generation of a sufficiently high anti-P10s immunoglobulin-G response
Safety and tolerability of the combination of vaccine and chemotherapy

This was defined as a >4-fold increase in a subject's anti-P10s-MAP IgG titer at Week 7 or later (at least 4 weeks after the 3rd immunization) relative to her pre-immune titer. For 1 participant, the Week 7 antibody titer was NA.

Posted

Count of Participants

Participants

At the time of definitive surgery (4-8 weeks after chemo, which is between Week 22 and Week 25)

ID	Title	Description
OG000	Part 1 - Chemovax Schedule A	Feasibility - Chemovax schedule A: Subjects will receive the first cycle of chemotherapy along with the first injection of P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine on week 1, the subsequent two injections of the vaccine one week apart (week 2 and 3), second cycle of chemotherapy on week 4, and subsequent cycles of chemotherapy every 21 days (week 7,10,13,16,19,22). Chemovax - P10s-PADRE/ MONTANIDE™ ISA 51 VG + Doxorubicin + Cyclophosphamide + Docetaxel (or Paclitaxel): Eligible subjects will be enrolled and immunized by SC administration of P10s-PADRE vaccine on each of 3 separate occasions over a three-week period.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Part 1 - Chemovax Schedule A	Feasibility - Chemovax schedule A: Subjects will receive the first cycle of chemotherapy along with the first injection of P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine on week 1, the subsequent two injections of the vaccine one week apart (week 2 and 3), second cycle of chemotherapy on week 4, and subsequent cycles of chemotherapy every 21 days (week 7,10,13,16,19,22). Chemovax - P10s-PADRE/ MONTANIDE™ ISA 51 VG + Doxorubicin + Cyclophosphamide + Docetaxel (or Paclitaxel): Eligible subjects will be enrolled and immunized by SC administration of P10s-PADRE vaccine on each of 3 separate occasions over a three-week period.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Jun 2, 2022	Dec 19, 2023	Prot_SAP_000.pdf
ICF	No	No	Yes	Informed Consent Form	Oct 6, 2021	Dec 20, 2023	ICF_002.pdf

ID	Term
D009371	Neoplasms by Site
D009369	Neoplasms
D001941	Breast Diseases
D012871	Skin Diseases

ID	Term
D003630	Daunorubicin
D018943	Anthracyclines
D009279	Naphthacenes
D011084	Polycyclic Aromatic Hydrocarbons

ID	Term
D004317	Doxorubicin
D003520	Cyclophosphamide
D000077143	Docetaxel