Vaccination of Triple Negative Breast Cancer Patients | NCT02938442

NCT02938442

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
Chemotherapy Only Arm	Active Comparator	Subjects randomized to the control arm will receive SoC neoadjuvant chemotherapy starting on week 1. Doxorubicin and cyclophosphamide (AC) will be administered concurrently every two weeks for four cycles with pegfilgrastim (or equivalent growth factor) on day 2 of each AC cycle, followed by paclitaxel weekly x 12 weeks.	Drug: Doxorubicin Drug: Cyclophosphamide Drug: Paclitaxel
Chemo+Vaccine Arm	Experimental	Subjects randomized to the chemo+vaccine arm will be immunized with P10s-PADRE in MONTANIDE™ ISA 51 VG a total of three times. The vaccine will be administered on weeks 1, 2 and 3 prior to chemotherapy. Then, they will start their SoC neoadjuvant chemotherapy on week 4. Doxorubicin and cyclophosphamide (AC) will be administered concurrently every two weeks for four cycles with pegfilgrastim (or equivalent growth factor) on day 2 of each AC cycle, followed by paclitaxel weekly x 12 weeks.	Biological: P10s-PADRE with MONTANIDE™ ISA 51 VG Drug: Doxorubicin Drug: Cyclophosphamide Drug: Paclitaxel

Interventions

Name	Type	Description	Arm Group Labels	Other Names
P10s-PADRE with MONTANIDE™ ISA 51 VG	Biological	Subjects randomized to the control arm will receive SoC neoadjuvant chemotherapy starting on week 1. Doxorubicin and cyclophosphamide (AC) will be administered concurrently every two weeks for four cycles with pegfilgrastim (or equivalent growth factor) on day 2 of each AC cycle, followed by paclitaxel weekly x 12 weeks.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Safety and Tolerability Adverse Events	A Safety/Tolerability Event is defined as the occurrence of one of the following: A Serious Adverse Event, OR A non-Serious Adverse Event of Grade = 3, 4, or 5, OR A non-Serious Adverse Event of Grade = 2 whose Relationship to P10s-PADRE Vaccine was classified as Definite, Probable, or Possible	From the start of treatment to the time of definitive surgery (4-8 weeks after chemo); from Week 0 to Week 20-23
Pathologic Complete Response (pCR)	A tumor-response call of either ypT0N0 or ypTisN0 determined through surgical staging after neoadjuvant therapy. The staging system used to determine the tumor-response call is the AJCC Staging System described in a 2014 FDA Guidance for Industry. • A tumor-response call of "pyT0N0" is also equated with pCR in the published literature.	During and/or Immediately After Surgery
Pathological Tumor Size	Tumor size at surgery/pathology report	Surgery
Pathological Node Status: Number of Positive Lymph Nodes	Number of positive lymph nodes found out of dissected lymph nodes	Surgery
Pathological Node Status: Number of Dissected Lymph Nodes	Number of dissected lymph nodes at surgery for study participants	Surgery
Tumor Response	Participants had their tumors surgically removed and pathologically staged using the AJCC Staging criteria. The main method of pathologic staging for breast cancer is the TNM system which stands for (Tumor size, lymph Node status and Metastases). "yp" prior to TN means the tissue was staged after neoadjuvant therapy. The larger the number after "T" means the larger the size, and the larger the number after "N" means the number of affected nearby lymph nodes. Therefore, tumor gradings with T3Nx are worse than those with T0Nx. The two categories "pyT0N0" and "ypT0N0" are both considered to be synonymous with pCR in the published literature.

Secondary Outcomes

Measure	Description	Time Frame
Fold Increase in P10s-MAP-Reactive Immunoglobulin Titers	The anti-P10s binding level was measured via ELISA method after incubation with a subject's serum samples. The endpoint titer was determined for each serum sample, and then fold change in endpoint titer in post-treatment weeks compared to pre-treatment week (Week 1) were calculated.	Weeks 7, 10, 15, 18, 23, 46, and 70

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Females of all races with biopsy-proven clinical stage I, II, or III TNBC (ER-negative, PR-negative and HER2-negative) 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-positive, PR-positive, 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 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 (Week 46 visit). Concurrent enrollment in observational studies is allowed.

Name	Affiliation	Role
Sindhu Malapati, 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

Arm/Group Information

ID	Title	Description
FG000	Chemotherapy Only	Subjects randomized to the control arm will receive SoC neoadjuvant chemotherapy starting on week 1. Doxorubicin and cyclophosphamide (AC) will be administered concurrently every two weeks for four cycles with pegfilgrastim (or equivalent growth factor) on day 2 of each AC cycle, followed by paclitaxel weekly x 12 weeks. Doxorubicin + Cyclophosphamide + Paclitaxel: Eligible subjects will be enrolled and receive standard neoadjuvant chemotherapy alone
FG001	Chemo+Vaccine	Subjects randomized to the chemo+vaccine arm will be immunized with P10s-PADRE in MONTANIDE™ ISA 51 VG a total of three times. The vaccine will be administered on weeks 1, 2 and 3 prior to chemotherapy. Then, they will start their SoC neoadjuvant chemotherapy on week 4. Doxorubicin and cyclophosphamide (AC) will be administered concurrently every two weeks for four cycles with pegfilgrastim (or equivalent growth factor) on day 2 of each AC cycle, followed by paclitaxel weekly x 12 weeks. P10s-PADRE with MONTANIDE™ ISA 51 VG + Doxorubicin + Cyclophosphamide + 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 in combination with standard neoadjuvant chemotherapy.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Chemotherapy Only	Subjects randomized to the control arm will receive SoC neoadjuvant chemotherapy starting on week 1. Doxorubicin and cyclophosphamide (AC) will be administered concurrently every two weeks for four cycles with pegfilgrastim (or equivalent growth factor) on day 2 of each AC cycle, followed by paclitaxel weekly x 12 weeks. Doxorubicin + Cyclophosphamide + Paclitaxel: Eligible subjects will be enrolled and receive standard neoadjuvant chemotherapy alone

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

Safety and Tolerability Adverse Events

A Safety/Tolerability Event is defined as the occurrence of one of the following:

A Serious Adverse Event, OR
A non-Serious Adverse Event of Grade = 3, 4, or 5, OR
A non-Serious Adverse Event of Grade = 2 whose Relationship to P10s-PADRE Vaccine was classified as Definite, Probable, or Possible

Posted

Number

Total events

From the start of treatment to the time of definitive surgery (4-8 weeks after chemo); from Week 0 to Week 20-23

ID	Title	Description
OG000	Chemotherapy Only	Subjects randomized to the control arm will receive SoC neoadjuvant chemotherapy starting on week 1. Doxorubicin and cyclophosphamide (AC) will be administered concurrently every two weeks for four cycles with pegfilgrastim (or equivalent growth factor) on day 2 of each AC cycle, followed by paclitaxel weekly x 12 weeks. Doxorubicin + Cyclophosphamide + Paclitaxel: Eligible subjects will be enrolled and receive standard neoadjuvant chemotherapy alone

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	Control Arm	Control arm: SoC neoadjuvant chemotherapy starting week 1. Doxorubicin and cyclophosphamide (AC) will be administered concurrently every two weeks for four cycles with pegfilgrastim (or equivalent growth factor) on day 2 of each AC cycle, followed by paclitaxel weekly x 12 weeks. Doxorubicin: Chemo+vaccine arm will be immunized with P10s-PADRE in MONTANIDE™ ISA 51 VG a total of three times. The vaccine will be administered on weeks 1, 2 and 3 prior to chemotherapy. Then, they will start their SoC neoadjuvant chemotherapy on week 4. Doxorubicin and cyclophosphamide (AC) will be administered concurrently every two weeks for four cycles with pegfilgrastim (or equivalent growth factor) on day 2 of each AC cycle, followed by paclitaxel weekly x 12 weeks. Cyclophosphamide: chemo+vaccine arm will be immunized with P10s-PADRE in MONTANIDE™ ISA 51 VG three times. Vaccine administered on weeks 1, 2 and 3 prior to chemotherapy. Subject will start their SoC neoadjuvant chemotherapy on week 4 as described above. Paclitaxel: chemo+vaccine arm immunized with P10s-PADRE in MONTANIDE™ ISA 51 VG three times. The vaccine will be administered on weeks 1, 2 and 3 prior to chemotherapy. Then, they will start their SoC neoadjuvant chemotherapy on week 4 as described above

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 18, 2023	Prot_SAP_000.pdf
ICF	No	No	Yes	Informed Consent Form	Oct 6, 2021	Dec 20, 2023	ICF_002.pdf

ID	Term
D064726	Triple Negative Breast Neoplasms
D001943	Breast Neoplasms

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