Clinical trial NCT02938442: Vaccination of Triple Negative Breast Cancer Patients
Official title: A Combined Phase i/II Efficacy Study of a Carbohydrate Mimotope-based Vaccine With MONTANIDE™ ISA 51 VG STERILE Combined With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Triple Negative Breast Cancer
Breast Neoplasms
Keywords: clinical stage I, II or III
TNBC
ER positive
PR positive
HER2 positive
Lead sponsor: University of Arkansas
Sponsor class: OTHER
First posted: 2016-10-19
Enrollment: 16
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: The purpose of this study is to evaluate an investigational agent, P10s-PADRE, a peptide mimotope-based vaccine, in combination with standard neoadjuvant chemotherapy in patients with clinical stage I, II or III estrogen-receptor (ER) negative, progesterone receptor (PR) negative and HER2-negative (= triple negative - TN) breast cancer. P10s-PADRE will be administered with MONTANIDE™ ISA 51 VG as adjuvant. Human breast cancers that express Tumor Associated Carbohydrate Antigens (TACAs) can be immunogenic, and enhancing the anti-TACA antibodies and immune effector function already present may augment the cytotoxic effects of standard therapies.

A randomized two-arm, open-label, multi-center phase I/II trial is designed with the goal being to evaluate the efficacy of combining vaccination of the P10s-PADRE formulation with neoadjuvant chemotherapy. Patients will be randomly assigned in a 2:1 ratio to standard chemotherapy plus P10s-PADRE or to standard chemotherapy alone. Efficacy will be based on the rate of pathologic Complete Response (pCR) observed among TN breast-cancer patients treated with the combination as compared with the group of patients who receive standard chemotherapy alone.

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.

Primary outcomes:
measure: Safety and Tolerability Adverse Events
timeFrame: From the start of treatment to the time of definitive surgery (4-8 weeks after chemo); from Week 0 to Week 20-23
measure: Pathologic Complete Response (pCR)
timeFrame: During and/or Immediately After Surgery
measure: Pathological Tumor Size
timeFrame: Surgery
measure: Pathological Node Status: Number of Positive Lymph Nodes
timeFrame: Surgery
measure: Pathological Node Status: Number of Dissected Lymph Nodes
timeFrame: Surgery
measure: Tumor Response
timeFrame: Surgery
Secondary outcomes:
measure: Fold Increase in P10s-MAP-Reactive Immunoglobulin Titers
timeFrame: Weeks 7, 10, 15, 18, 23, 46, and 70
measure: Frequencies of NK Cells - CD16
timeFrame: Week 1, 7, 10, 15, 18, 23, 46, 70
measure: Frequencies of NK Cells - CD69
timeFrame: Weeks 1, 7, 10, 15, 18, 23, 46, and 70
measure: Frequencies of NK Cells - NKp46
timeFrame: Weeks 1, 7, 10, 15, 18, 23, 46, and 70
measure: Frequencies of NK Cells - NKG2D
timeFrame: Weeks 1, 7, 10, 15, 18, 23, 46, and 70
measure: Frequencies of T Cells - CD3+/CD4+
timeFrame: Weeks 1, 7, 10, 15, 18, 23, and 46
measure: Frequencies of T Cells - CD3+/CD8+
timeFrame: Weeks 1, 7, 10, 15, 18, 23, and 46
measure: Frequencies of Cells - CD69+/CD3+
timeFrame: Weeks 1, 7, 10, 15, 18, 23, 46, and 70
measure: Frequencies of Circulating Regulatory T Cells (Tregs)
timeFrame: Weeks 1, 7, 10, 15, 18, 23, 46, and 70
measure: Activation Profiles of NK Cells: CD16
timeFrame: Weeks 1, 7, 10, 15, 18, 23, 46, and 70
measure: Activation Profiles of NK Cells: CD69
timeFrame: Weeks 1, 7, 10, 15, 18, 23, 46, and 70
measure: Activation Profiles of NK Cells: NKp46
timeFrame: Weeks 1, 7, 10, 15, 18, 23, 46, and 70
measure: Activation Profiles of NK Cells: NKG2D
timeFrame: Weeks 1, 7, 10, 15, 18, 23, 46, and 70
measure: Activation Profiles of T Cells - CD69 on CD3+
timeFrame: Weeks 1, 7, 10, 15, 18, 23, 46, 70
Other outcomes:
Locations:
city: Fayetteville
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
Study officials:
affiliation: University of Arkansas
name: Sindhu Malapati, MD
role: PRINCIPAL_INVESTIGATOR
References: