Vaccination of High Risk Breast Cancer Patients

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

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Breast Neoplasms
• Intervention / Treatment: Biological: P10s-PADRE/ MONTANIDE™ ISA 51 VG; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Docetaxel

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)-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.

This combined Phase I/II feasibility-and-efficacy study will have three parts. Its first part will be a Phase I evaluation of the safety, tolerability, and feasibility of eliciting adequate IgG response with P10s-PADRE when administered in combination with SoC neoadjuvant chemotherapy. The study's second and third parts will respectively constitute Stages 1 and 2 of the Phase II primary-efficacy evaluation of Chemovax using a Simon optimal two-stage design

To evaluate the feasibility of eliciting adequate immune response with P10s-PADRE when it is administered in combination with neoadjuvant chemotherapy, we will sequentially evaluate different schedules of vaccination relative to chemotherapy, and stop evaluating as soon as we have identified a feasible schedule. To this end, we have defined five different Chemovax schedules, and named them A, B, C, D, and E;

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • Highlands Oncology Group
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 - Chemovax Schedule A; 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: P10s-PADRE/ MONTANIDE™ ISA 51 VG; Eligible subjects will be enrolled and immunized by SC administration of P10s-PADRE vaccine on each of 3 separate occasions concurrent with chemotherapy.; Drug: Doxorubicin; Doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) (AC) will be administered concurrently every three weeks for four cycles followed by docetaxel (75 mg/m2) every three weeks for four cycles.; Drug: Cyclophosphamide; Doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) (AC) will be administered concurrently every three weeks for four cycles followed by docetaxel (75 mg/m2) every three weeks for four cycles.; Drug: Docetaxel; Doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) (AC) will be administered concurrently every three weeks for four cycles followed by docetaxel (75 mg/m2) every three weeks for four cycles. If docetaxel is not tolerated, paclitaxel (175mg/m2) may be used in its place.
Experimental: Part 1 - Chemovax Schedule B; 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: P10s-PADRE/ MONTANIDE™ ISA 51 VG; Eligible subjects will be enrolled and immunized by SC administration of P10s-PADRE vaccine on each of 3 separate occasions concurrent with chemotherapy.; Drug: Doxorubicin; Doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) (AC) will be administered concurrently every three weeks for four cycles followed by docetaxel (75 mg/m2) every three weeks for four cycles.; Drug: Cyclophosphamide; Doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) (AC) will be administered concurrently every three weeks for four cycles followed by docetaxel (75 mg/m2) every three weeks for four cycles.; Drug: Docetaxel; Doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) (AC) will be administered concurrently every three weeks for four cycles followed by docetaxel (75 mg/m2) every three weeks for four cycles. If docetaxel is not tolerated, paclitaxel (175mg/m2) may be used in its place.
Experimental: Part 1 - Chemovax Schedule C; 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: P10s-PADRE/ MONTANIDE™ ISA 51 VG; Eligible subjects will be enrolled and immunized by SC administration of P10s-PADRE vaccine on each of 3 separate occasions concurrent with chemotherapy.; Drug: Doxorubicin; Doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) (AC) will be administered concurrently every three weeks for four cycles followed by docetaxel (75 mg/m2) every three weeks for four cycles.; Drug: Cyclophosphamide; Doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) (AC) will be administered concurrently every three weeks for four cycles followed by docetaxel (75 mg/m2) every three weeks for four cycles.; Drug: Docetaxel; Doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) (AC) will be administered concurrently every three weeks for four cycles followed by docetaxel (75 mg/m2) every three weeks for four cycles. If docetaxel is not tolerated, paclitaxel (175mg/m2) may be used in its place.
Experimental: Part 1 - Chemovax Schedule D; 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: P10s-PADRE/ MONTANIDE™ ISA 51 VG; Eligible subjects will be enrolled and immunized by SC administration of P10s-PADRE vaccine on each of 3 separate occasions concurrent with chemotherapy.; Drug: Doxorubicin; Doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) (AC) will be administered concurrently every three weeks for four cycles followed by docetaxel (75 mg/m2) every three weeks for four cycles.; Drug: Cyclophosphamide; Doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) (AC) will be administered concurrently every three weeks for four cycles followed by docetaxel (75 mg/m2) every three weeks for four cycles.; Drug: Docetaxel; Doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) (AC) will be administered concurrently every three weeks for four cycles followed by docetaxel (75 mg/m2) every three weeks for four cycles. If docetaxel is not tolerated, paclitaxel (175mg/m2) may be used in its place.
Experimental: Part 1 - Chemovax Schedule E; 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: P10s-PADRE/ MONTANIDE™ ISA 51 VG; Eligible subjects will be enrolled and immunized by SC administration of P10s-PADRE vaccine on each of 3 separate occasions concurrent with chemotherapy.; Drug: Doxorubicin; Doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) (AC) will be administered concurrently every three weeks for four cycles followed by docetaxel (75 mg/m2) every three weeks for four cycles.; Drug: Cyclophosphamide; Doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) (AC) will be administered concurrently every three weeks for four cycles followed by docetaxel (75 mg/m2) every three weeks for four cycles.; Drug: Docetaxel; Doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) (AC) will be administered concurrently every three weeks for four cycles followed by docetaxel (75 mg/m2) every three weeks for four cycles. If docetaxel is not tolerated, paclitaxel (175mg/m2) may be used in its place.
Experimental: Part 2 - Chemovax Schedule C; 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: P10s-PADRE/ MONTANIDE™ ISA 51 VG; Eligible subjects will be enrolled and immunized by SC administration of P10s-PADRE vaccine on each of 3 separate occasions concurrent with chemotherapy.; Drug: Doxorubicin; Doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) (AC) will be administered concurrently every three weeks for four cycles followed by docetaxel (75 mg/m2) every three weeks for four cycles.; Drug: Cyclophosphamide; Doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) (AC) will be administered concurrently every three weeks for four cycles followed by docetaxel (75 mg/m2) every three weeks for four cycles.; Drug: Docetaxel; Doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) (AC) will be administered concurrently every three weeks for four cycles followed by docetaxel (75 mg/m2) every three weeks for four cycles. If docetaxel is not tolerated, paclitaxel (175mg/m2) may be used in its place.
Experimental: Part 3 - Chemovax Schedule C; 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: P10s-PADRE/ MONTANIDE™ ISA 51 VG; Eligible subjects will be enrolled and immunized by SC administration of P10s-PADRE vaccine on each of 3 separate occasions concurrent with chemotherapy.; Drug: Doxorubicin; Doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) (AC) will be administered concurrently every three weeks for four cycles followed by docetaxel (75 mg/m2) every three weeks for four cycles.; Drug: Cyclophosphamide; Doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) (AC) will be administered concurrently every three weeks for four cycles followed by docetaxel (75 mg/m2) every three weeks for four cycles.; Drug: Docetaxel; Doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) (AC) will be administered concurrently every three weeks for four cycles followed by docetaxel (75 mg/m2) every three weeks for four cycles. If docetaxel is not tolerated, paclitaxel (175mg/m2) may be used in its place.

What is the study measuring?

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)
Determine the pCR Rate	The patient-level primary outcome for this objective is pathological Complete Response (pCR), which is binary yes/no, and the study-level endpoint for this outcome is the rate of pCR, i.e. the percentage of patients that achieved pCR=yes. The patient is assessed at the time of surgery for whether they achieved pCR=yes. They have to do the surgery in order to obtain the tissue samples on which they do their pCR assessment. Pathological Complete Response is defined as the absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes following completion of neoadjuvant systemic therapy (i.e., ypT0N0 or ypTisN0 in the AJCC staging system for staging solid tumors in the neoadjuvant setting that was described in a 2014 FDA Guidance for Industry).	At the time of definitive surgery (4-8 weeks after chemo, which is between Week 22 and Week 25)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
P10s-MAP-Reactive Immunoglobulin Titers	The anti-P10s binding level was measured via ELISA method after incubation with a subject's serum or plasma sample. Data was collected at multiple timepoints throughout the study. Values were averaged for each group.	Week 1 through Week 70
Activation Profiles of NK Cells: Pre-Immune and Post-Immune CD16	Activated-NK-cell profiles will be determined via flow cytometry as the expression levels of different activation markers on NK cells in the subject's blood sample. Data was collected at multiple timepoints throughout the study. Values were averaged for each group. For some participants, CD16 was not assessable.	Week 1 through Week 70
Activation Profiles of NK Cells: Pre-Immune and Post-Immune CD69	Activated-NK-cell profiles will be determined via flow cytometry as the expression levels of different activation markers on NK cells in the subject's blood sample. Data was collected at multiple timepoints throughout the study. Values were averaged for each group. For some participants, CD69 was not assessable.	Week 1 through Week 70
Activation Profiles of NK Cells: Pre-Immune and Post-Immune NKp46	Activated-NK-cell profiles will be determined via flow cytometry as the expression levels of different activation markers on NK cells in the subject's blood sample. Data was collected at multiple timepoints throughout the study. Values were averaged for each group. For some participants, NKp46 was not assessable.	Week 1 through Week 70

Collaborators and Investigators

• Sponsor: University of Arkansas
• Investigators: Principal Investigator: Sri Obulareddy, MD, University of Arkansas

Publications and helpful links

General Publications

• Hernandez Puente CV, Hsu PC, Rogers LJ, Jousheghany F, Siegel E, Kadlubar SA, Beck JT, Makhoul I, Hutchins LF, Kieber-Emmons T, Monzavi-Karbassi B. Association of DNA-Methylation Profiles With Immune Responses Elicited in Breast Cancer Patients Immunized With a Carbohydrate-Mimicking Peptide: A Pilot Study. Front Oncol. 2020 Jun 5;10:879. doi: 10.3389/fonc.2020.00879. eCollection 2020.

Study record dates

Study Major Dates

• Study Start (Actual): January 14, 2015
• Primary Completion (Actual): January 3, 2023
• Study Completion (Actual): January 3, 2023

Study Registration Dates

• First Submitted: August 26, 2014
• First Submitted That Met QC Criteria: August 27, 2014
• First Posted (Estimated): August 29, 2014

Study Record Updates

• Last Update Posted (Actual): November 7, 2024
• Last Update Submitted That Met QC Criteria: November 5, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: HER2 negative; clinical stage I, II or III; ER postive
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Antibiotics, Antineoplastic; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Topoisomerase Inhibitors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Topoisomerase II Inhibitors; Adjuvants, Immunologic; Docetaxel; Monatide (IMS 3015); Cyclophosphamide; Doxorubicin
• Other Study ID Numbers: 202556

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No