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Efficacy and Safety Study of NeuVax™ (Nelipepimut-S or E75) Vaccine to Prevent Breast Cancer Recurrence (PRESENT)

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ClinicalTrials.gov Identifier: NCT01479244
Recruitment Status : Completed
First Posted : November 24, 2011
Last Update Posted : February 27, 2017
Sponsor:
Information provided by (Responsible Party):
Galena Biopharma, Inc.

Tracking Information
First Submitted Date  ICMJE November 20, 2011
First Posted Date  ICMJE November 24, 2011
Last Update Posted Date February 27, 2017
Study Start Date  ICMJE November 2011
Actual Primary Completion Date September 21, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 21, 2014)
Comparison of DFS in vaccine treated patients and control patients [ Time Frame: 36 months ]
The primary objective is to compare the DFS in subjects with operable early-stage, node-positive breast cancer who receive standard of care multimodality therapy plus NeuVax™ as the treatment group or standard of care multimodality therapy plus the vaccine adjuvant, Leukine® as the control group.
Original Primary Outcome Measures  ICMJE
 (submitted: November 22, 2011)
Comparison of disease-free survival in vaccine treated patients and control patients [ Time Frame: 36 months ]
The primary objective is to compare the disease-free survival (DFS) in subjects with operable early-stage, node-positive breast cancer who receive standard of care multimodality therapy plus NeuVax™ as the treatment group or standard of care multimodality therapy plus the vaccine adjuvant, GM-CSF as the control group.
Change History Complete list of historical versions of study NCT01479244 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 21, 2014)
Assessment of DFS and OS at 3, 5 and 10 years in vaccine and control groups, respectively; assessment of safety [ Time Frame: 3 through 10 years ]
The secondary objectives are to evaluate the 2 groups of subjects for:
  • 5- and 10-year DFS
  • 3-year OS
  • 5- and 10-year OS
  • Time to recurrence (TTR), time to local recurrence (TTLR), time to distant recurrence (TTDR), time to bone metastases (TTBM)
  • Overall safety profile and adverse events (AEs)
Original Secondary Outcome Measures  ICMJE
 (submitted: November 22, 2011)
Assessment of Disease-Free Survival and Overall Survival at 3, 5 and 10 years in vaccine and control groups, respectively; assessment of safety [ Time Frame: 3 through 10 years ]
The secondary objectives are to evaluate the 2 groups of subjects for:
  • 5- and 10-year DFS
  • 3-year Overall survival (OS)
  • 5- and 10-year OS
  • Time to recurrence (TTR), time to local recurrence (TTLR), time to distant recurrence (TTDR), time to bone metastases (TTBM)
  • Overall safety profile and adverse events (AEs)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety Study of NeuVax™ (Nelipepimut-S or E75) Vaccine to Prevent Breast Cancer Recurrence
Official Title  ICMJE PRESENT: Prevention of Recurrence in Early-Stage, Node-Positive Breast Cancer With Low to Intermediate HER2 Expressions With NeuVax™Treatment
Brief Summary

Purpose of this trial:

  1. To assess the efficacy and safety of NeuVax™ administered with adjuvant Leukine® (sargramostim, GM-CSF).
  2. To evaluate and compare the disease free survival (DFS) in the vaccinated and control subjects.
Detailed Description

This is a multicenter, multinational, prospective, randomized, double-blind, controlled Phase 3 study.

The subjects eligible for this trial have an early stage node-positive breast cancer. Their tumors express low or intermediate levels of the HER2 protein. NeuVax™ will be administered after completion of front-line, standard of care therapy (surgery, radiation therapy, and chemotherapy) and can be given concomitantly with physician prescribed endocrine treatment.

NeuVax™ is the immmunodominant nonapeptide derived from the extracellular domain of the HER2 protein, a well-established target for therapeutic intervention in breast carcinoma. The nelipepimut sequence stimulates specific CD8+ cytotoxic T lymphocytes (CTL) following binding to HLA-A2/A3 molecules on antigen presenting cells (APC). These activated specific CTLs recognize, neutralize and destroy through cell lysis HER2 expressing cancer cells, including occult cancer cells and micrometastatic foci. The nelipepimut immune response can also generate CTLs to other immunogenic peptides through inter- and intra-antigenic epitope spreading. Based on a successful Phase 2 trial, which achieved its primary endpoint of DFS, the Food and Drug Administration (FDA) granted NeuVax a Special Protocol Assessment (SPA) for its Phase 3 PRESENT (Prevention of Recurrence in Early-Stage, Node-Positive Breast Cancer with Low to Intermediate HER2 Expression with NeuVax Treatment) study.

The active portion of the study will last three years (36 months). The follow-up will last from 5 to 10 years.

Endpoints:

  1. Primary efficacy endpoint:

    • 3-year DFS
  2. Secondary efficacy endpoints:

    • 5- and 10-year DFS
    • 3-year OS
    • 5- and 10-year OS
    • Safety profile, and adverse events (AEs)
    • Patterns of recurrence to include Time to recurrence (TTR), time to local recurrence (TTLR), time to distant recurrence (TTDR), time to bone metastases (TTBM)

Safety Assessments:

Subjects will be assessed at every study visit for the safety endpoints, AEs,vital signs, physical examinations and laboratory data; yearly follow-up of survival will include imaging studies, ECGs, MUGA or ECHO scans and concomitant medications.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE Breast Cancer With Low to Intermediate HER2 Expression
Intervention  ICMJE
  • Biological: NeuVax™ vaccine
    E75 peptide acetate (HER2/neu p366-379) in WFI (1.5 mg/mL) mixed with 250 micrograms Leukine® (sargramostim, GM-CSF), will be administered in intradermal injections, in four divided doses (4 sites on upper thigh) once a month, for six consecutive months. At the end of the six months, NeuVax™ vaccine boosters will be given the same way once every six months for the next five times (totaling 36 months).
    Other Name: E75 peptide acetate , WFI, sargramostim, GM-CSF
  • Biological: Leukine® (sargramostim, GM-CSF) and water for injection
    Leukine® 250 micrograms in water for injection, will be administered in intradermal injections, in four divided doses (4 sites on upper thigh) once a month, for six consecutive months. At the end of the six months, boosters inoculations will be given the same way once every six months for the next five times (totaling 36 months).
    Other Name: Leukine®
Study Arms  ICMJE
  • Experimental: NeuVax™
    NeuVax™ in WFI solution with Leukine®
    Intervention: Biological: NeuVax™ vaccine
  • Active Comparator: Leukine®
    Leukine® with WFI
    Intervention: Biological: Leukine® (sargramostim, GM-CSF) and water for injection
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 23, 2017)
758
Original Estimated Enrollment  ICMJE
 (submitted: November 22, 2011)
700
Actual Study Completion Date  ICMJE September 21, 2016
Actual Primary Completion Date September 21, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  • Pathological diagnosis of invasive adenocarcinoma of the breast
  • Breast cancer completely excised, or patient receiving neoadjuvant therapy prior to surgery
  • One of these 2 surgical treatments and axillary staging with sentinel lymph node dissection or axillary dissection level I/II:

    1. Total mastectomy-patients with a positive sentinel lymph node must have undergone a completion axillary dissection level I/II
    2. BCS (lumpectomy)-patients with a positive sentinel lymph node must have undergone a completion axillary dissection level I/II unless they had clinically node negative T1-T2 tumors and fewer than 3 involved lymph nodes
  • Node-positive disease
  • Primary tumor stage T1-3 at initial diagnosis
  • HER2 negative (HER2 1+ by IHC or HER2 2+ by IHC/FISH)
  • HLA-A2 or HLA-A3 haplotype
  • Completed NCCN approved neo-adjuvant/adjuvant chemotherapy or both
  • Completed radiation therapy
  • No evidence of disease
  • Able and willing (or have legal representative) to understand the study and provide consent

Key Exclusion Criteria:

  • Bilateral breast malignancy or suspicious mass in opposite breast
  • Inflammatory breast malignancy
  • History of prior breast cancer, ductal carcinoma in situ
  • Prior trastuzumab therapy
  • New York Heart Association Stage 3 or 4 cardiac disease
  • Sensory/motor neuropathy ≥ Grade 2
  • Autoimmune diseases or immune deficiency disease
  • Subjects on chronic steroid therapy, other immunosuppressive therapy
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States,   Bulgaria,   Canada,   Czech Republic,   France,   Germany,   Hungary,   Israel,   Poland,   Romania,   Russian Federation,   Ukraine,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01479244
Other Study ID Numbers  ICMJE NeuVax™ PH3-01, BB-IND 009187
2011-005219-98 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Galena Biopharma, Inc.
Study Sponsor  ICMJE Galena Biopharma, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Elizabeth A Mittendorf, MD,FACS M.D. Anderson Cancer Center
PRS Account Galena Biopharma, Inc.
Verification Date February 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP