Vaccination of Triple Negative Breast Cancer Patients

Study Overview
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Brief Summary
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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
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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 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.

Official Title
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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

Conditions
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Triple Negative Breast Cancer, Breast Neoplasms

Intervention / Treatment
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* Biological: P10s-PADRE with MONTANIDE™ ISA 51 VG + Doxorubicin + Cyclophosphamide + Paclitaxel
* Drug: Doxorubicin + Cyclophosphamide + Paclitaxel


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control Arm<br>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 + Cyclophosphamide + Paclitaxel<br>* Eligible subjects will be enrolled and receive standard neoadjuvant chemotherapy alone<br>* Other names: Standard neoadjuvant chemotherapy;|
| Experimental: Chemo+Vaccine Arm<br>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 + Doxorubicin + Cyclophosphamide + Paclitaxel<br>* 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.<br>* Other names: P10s-PADRE/ MONTANIDE™ ISA 51 VG with standard neoadjuvant chemotherapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety/tolerability | Monitor the safety and tolerability of the investigational product, P10s-PADRE in MONTANIDETM ISA 51 VG, when it is administered in combination with SoC Neoadjuvant chemotherapy. | At the time of definitive surgery (4-8 weeks after chemo); between Week 20 and Week 23 | 
| Demonstration of clinical response | Determine if the Chemo+vaccine regimen in TNBC would lead to a significantly higher rate of pCR in breast and axillary nodes at time of definitive surgery compared to the pCR rate of 40% expected on the control arm | [Time Frame: Week 70 (±4 weeks) per subject] | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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clinical stage I, II or III, TNBC, ER positive, PR positive, HER2 positive