Vaccination of Triple Negative Breast Cancer Patients

NCT02938442 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 206010
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to evaluate a new investigational cancer vaccine, P10s-PADRE in combination with standard neoadjuvant chemotherapy and surgery in patients with clinical stage I, II or III triple negative breast cancer (TNBC). This study will compare the vaccine plus standard neoadjuvant chemotherapy and surgery to standard neoadjuvant chemotherapy and surgery alone.

Conditions

Triple Negative Breast Cancer; Breast Neoplasms

Keywords

clinical stage I, II or III; TNBC; ER positive; PR positive; HER2 positive

Outcome Measures

Primary Outcomes (6)

• 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.

  Surgery

Secondary Outcomes (14)

• Fold Increase in P10s-MAP-Reactive Immunoglobulin Titers

  Weeks 7, 10, 15, 18, 23, 46, and 70

• Frequencies of NK Cells - CD16

  Week 1, 7, 10, 15, 18, 23, 46, 70

• Frequencies of NK Cells - CD69

  Weeks 1, 7, 10, 15, 18, 23, 46, and 70

• Frequencies of NK Cells - NKp46

  Weeks 1, 7, 10, 15, 18, 23, 46, and 70

• Frequencies of NK Cells - NKG2D

  Weeks 1, 7, 10, 15, 18, 23, 46, and 70

Study Arms (2)

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

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.

Also known as: P10s-PADRE/ MONTANIDE™ ISA 51 VG

Chemo+Vaccine Arm

Doxorubicin DRUG

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.

Chemo+Vaccine Arm; Chemotherapy Only Arm

Cyclophosphamide DRUG

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.

Chemo+Vaccine Arm; Chemotherapy Only Arm

Paclitaxel DRUG

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.

Chemo+Vaccine Arm; Chemotherapy Only Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Arkansas: lead

Study Sites (2)

Highlands Oncology Group

Fayetteville, Arkansas, 72703, United States

Location

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Breast Neoplasms

Interventions

Doxorubicin; Cyclophosphamide; Paclitaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes

Results Point of Contact

• Title: Sorena Lo
• Organization: University of Arkansas for Medical Sciences

SBLo@uams.edu

5016868274

Study Officials

• Sindhu Malapati, MD

  University of Arkansas

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 17, 2016
• First Posted: October 19, 2016
• Study Start: January 25, 2019
• Primary Completion: January 9, 2023
• Study Completion: January 9, 2023
• Last Updated: November 7, 2024
• Results First Posted: July 5, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)