Breast CancerPhase 1/2NCT02229084
Vaccination of High Risk Breast Cancer Patients - A Combined Phase I/II Feasibility-and-Efficacy Study
A Phase 1/2 study testing P10s-PADRE/ MONTANIDE™ ISA 51 VG, Doxorubicin and Cyclophosphamide in people with Breast Cancer and Breast Neoplasms, run by University of Arkansas at 2 sites in United States.
Trial 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 estrogen-receptor (ER)-positive, HER2-negative breast cancer. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer, Breast Neoplasms
- What is being tested?
- P10s-PADRE/ MONTANIDE™ ISA 51 VG, Doxorubicin and Cyclophosphamide
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- 2 sitesUnited States
- Study dates
- 14 Jan 2015to 3 Jan 2023
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Highlands Oncology Group
Fayetteville, Arkansas, 72703
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205
About this study
Official title: 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.
Read the 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;
- Conditions
- Breast Cancer, Breast Neoplasms
- Being tested
- P10s-PADRE/ MONTANIDE™ ISA 51 VG, Doxorubicin, Cyclophosphamide, Docetaxel
- Keywords
- clinical stage I, II or III, ER postive, HER2 negative
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
P10s-PADRE/ MONTANIDE™ ISA 51 VGBiological
Eligible subjects will be enrolled and immunized by SC administration of P10s-PADRE vaccine on each of 3 separate occasions concurrent with chemotherapy.
DoxorubicinDrug
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.
CyclophosphamideDrug
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.
DocetaxelDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Part 1 - Chemovax Schedule A | Experimental | 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). Receives: Biological: P10s-PADRE/ MONTANIDE™ ISA 51 VG; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Docetaxel |
| Part 1 - Chemovax Schedule B | Experimental | 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). Receives: Biological: P10s-PADRE/ MONTANIDE™ ISA 51 VG; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Docetaxel |
| Part 1 - Chemovax Schedule C | Experimental | 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). Receives: Biological: P10s-PADRE/ MONTANIDE™ ISA 51 VG; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Docetaxel |
| Part 1 - Chemovax Schedule D | Experimental | 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). Receives: Biological: P10s-PADRE/ MONTANIDE™ ISA 51 VG; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Docetaxel |
| Part 1 - Chemovax Schedule E | Experimental | 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). Receives: Biological: P10s-PADRE/ MONTANIDE™ ISA 51 VG; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Docetaxel |
| Part 2 - Chemovax Schedule C | Experimental | 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). Receives: Biological: P10s-PADRE/ MONTANIDE™ ISA 51 VG; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Docetaxel |
| Part 3 - Chemovax Schedule C | Experimental | 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). Receives: Biological: P10s-PADRE/ MONTANIDE™ ISA 51 VG; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Docetaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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).
Measured: At the time of definitive surgery (4-8 weeks after chemo, which is between Week 22 and Week 25)
Secondary outcomes (4)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Week 1 through Week 70
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2014 (estimated)
- Study start14 Jan 2015
- Primary completion3 Jan 2023
- Study completion3 Jan 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- 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)
- Enrolment
- 58 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Arkansas
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sri Obulareddy, MD, Principal investigator, University of Arkansas
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02229084
- Sponsor's protocol ID
- 202556
- Status last verified
- Sep 2026
- First submitted
- 26 Aug 2014
- Last updated
- 6 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
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.
PubMed 32582547