Vaccination of High Risk Breast Cancer Patients

NCT02229084 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 202556
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 2

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 estrogen-receptor (ER)-positive, HER2-negative breast cancer.

Conditions

Breast Cancer; Breast Neoplasms

Keywords

clinical stage I, II or III; ER postive; HER2 negative

Outcome Measures

Primary Outcomes (2)

• 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 1. Generation of a sufficiently high anti-P10s immunoglobulin-G response 2. 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 Outcomes (4)

• P10s-MAP-Reactive Immunoglobulin Titers

  Week 1 through Week 70

• Activation Profiles of NK Cells: Pre-Immune and Post-Immune CD16

  Week 1 through Week 70

• Activation Profiles of NK Cells: Pre-Immune and Post-Immune CD69

  Week 1 through Week 70

• Activation Profiles of NK Cells: Pre-Immune and Post-Immune NKp46

  Week 1 through Week 70

Study Arms (7)

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).

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).

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).

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).

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).

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).

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).

Biological: P10s-PADRE/ MONTANIDE™ ISA 51 VG; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Docetaxel

Interventions

P10s-PADRE/ MONTANIDE™ ISA 51 VG BIOLOGICAL

Eligible subjects will be enrolled and immunized by SC administration of P10s-PADRE vaccine on each of 3 separate occasions concurrent with chemotherapy.

Part 1 - Chemovax Schedule A; Part 1 - Chemovax Schedule B; Part 1 - Chemovax Schedule C; Part 1 - Chemovax Schedule D; Part 1 - Chemovax Schedule E; Part 2 - Chemovax Schedule C; Part 3 - Chemovax Schedule C

Doxorubicin DRUG

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.

Part 1 - Chemovax Schedule A; Part 1 - Chemovax Schedule B; Part 1 - Chemovax Schedule C; Part 1 - Chemovax Schedule D; Part 1 - Chemovax Schedule E; Part 2 - Chemovax Schedule C; Part 3 - Chemovax Schedule C

Cyclophosphamide DRUG

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.

Part 1 - Chemovax Schedule A; Part 1 - Chemovax Schedule B; Part 1 - Chemovax Schedule C; Part 1 - Chemovax Schedule D; Part 1 - Chemovax Schedule E; Part 2 - Chemovax Schedule C; Part 3 - Chemovax Schedule C

Docetaxel DRUG

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.

Part 1 - Chemovax Schedule A; Part 1 - Chemovax Schedule B; Part 1 - Chemovax Schedule C; Part 1 - Chemovax Schedule D; Part 1 - Chemovax Schedule E; Part 2 - Chemovax Schedule C; Part 3 - Chemovax Schedule C

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Arkansas: lead

Study Sites (2)

Highlands Oncology Group

Fayetteville, Arkansas, 72703, United States

Location

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Related Publications (1)

• 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.

  PMID: 32582547 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Doxorubicin; Cyclophosphamide; Docetaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes

Results Point of Contact

• Title: Sorena Lo
• Organization: University of Arkansas for Medical Sciences

SBLo@uams.edu

5016868274

Study Officials

• Sri Obulareddy, MD

  University of Arkansas

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: August 26, 2014
• First Posted: August 29, 2014
• Study Start: January 14, 2015
• Primary Completion: January 3, 2023
• Study Completion: January 3, 2023
• Last Updated: November 7, 2024
• Results First Posted: May 23, 2024

Record last verified: 2024-05

Locations

US (2)