Vaccination of High Risk 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 estrogen-receptor (ER)-positive, HER2-negative breast cancer.

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)-positive, HER2-negative breast cancer. This is a single-arm, multi-site Phase I/II study designed with the two goals being (1) to evaluate the feasibility of combining vaccination with the P10s-PADRE formulation with neoadjuvant chemotherapy and (2) to determine if the polymerase chain reaction (pCR) rate among ER-positive, HER2-negativebreast-cancer patients treated with the combination is significantly higher than the 8% rate observed among ER-positive breast-cancer subjects in a pooled analysis of seven randomized clinical trials. P10s-PADRE vaccine with MONTANIDE™ ISA 51 VG as adjuvant will be given in combination with neoadjuvant chemotherapy in female patients with clinical stage I, II or III ER-positive, HER2-negative breast cancer.

Official Title
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A Combined Phase I/II Feasibility-and-Efficacy Study of a Carbohydrate Mimotope-based Vaccine With MONTANIDE™ ISA 51 VG Combined With Neoadjuvant Chemotherapy

Conditions
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Breast Cancer, Breast Neoplasms

Intervention / Treatment
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* Biological: Chemovax - P10s-PADRE/ MONTANIDE™ ISA 51 VG + Doxorubicin + Cyclophosphamide + Docetaxel (or Paclitaxel)


Participation Criteria
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Eligibility Criteria
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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.

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: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: This combined Phase I/II feasibility-and-efficacy study will have three parts. Part 1 will be a Phase I evaluation of the safety, tolerability, and feasibility of the Chemovax to assess the timing of vaccination relative to chemotherapy. Five different Chemovax schedules (Schedule A, B, C, D, and E) will be sequentially evaluated. Once such a feasible schedule is identified, the study will proceed with its second and third parts. Part 2 (primary efficacy) and Part 3 (expanded efficacy) will respectively constitute Stages 1 and 2 of the Phase II primary-efficacy evaluation of Chemovax using a Simon optimal two-stage design.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1 - Chemovax Schedule A<br>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: Chemovax - P10s-PADRE/ MONTANIDE™ ISA 51 VG + Doxorubicin + Cyclophosphamide + Docetaxel (or 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.<br>* Other names: P10s-PADRE/ MONTANIDE™ ISA 51 VG with standard neoadjuvant chemotherapy;|
| Experimental: Part 1 - Chemovax Schedule B<br>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: Chemovax - P10s-PADRE/ MONTANIDE™ ISA 51 VG + Doxorubicin + Cyclophosphamide + Docetaxel (or 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.<br>* Other names: P10s-PADRE/ MONTANIDE™ ISA 51 VG with standard neoadjuvant chemotherapy;|
| Experimental: Part 1 - Chemovax Schedule C<br>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: Chemovax - P10s-PADRE/ MONTANIDE™ ISA 51 VG + Doxorubicin + Cyclophosphamide + Docetaxel (or 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.<br>* Other names: P10s-PADRE/ MONTANIDE™ ISA 51 VG with standard neoadjuvant chemotherapy;|
| Experimental: Part 1 - Chemovax Schedule D<br>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). | Biological: Chemovax - P10s-PADRE/ MONTANIDE™ ISA 51 VG + Doxorubicin + Cyclophosphamide + Docetaxel (or 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.<br>* Other names: P10s-PADRE/ MONTANIDE™ ISA 51 VG with standard neoadjuvant chemotherapy;|
| Experimental: Part 1 - Chemovax Schedule E<br>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). | Biological: Chemovax - P10s-PADRE/ MONTANIDE™ ISA 51 VG + Doxorubicin + Cyclophosphamide + Docetaxel (or 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.<br>* Other names: P10s-PADRE/ MONTANIDE™ ISA 51 VG with standard neoadjuvant chemotherapy;|
| Experimental: Part 2 - Chemovax Schedule C<br>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). | Biological: Chemovax - P10s-PADRE/ MONTANIDE™ ISA 51 VG + Doxorubicin + Cyclophosphamide + Docetaxel (or 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.<br>* Other names: P10s-PADRE/ MONTANIDE™ ISA 51 VG with standard neoadjuvant chemotherapy;|
| Experimental: Part 3 - Chemovax Schedule C<br>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). | Biological: Chemovax - P10s-PADRE/ MONTANIDE™ ISA 51 VG + Doxorubicin + Cyclophosphamide + Docetaxel (or 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.<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 |
| --- | --- | --- |
| 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) | 
| Demonstration of clinical response | Determine if the Chemovax regimen in ER-positive breast cancer would lead to a significantly higher rate of pCR in breast and axillary lymph nodes at time of definitive surgery compared to the corresponding rate reported by von Minckwitz et al. | Week 73 (±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, ER postive, HER2 negative