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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Galena Biopharma, Inc.
Sponsor:
Information provided by (Responsible Party):
Galena Biopharma, Inc.
ClinicalTrials.gov Identifier:
NCT01479244
First received: November 20, 2011
Last updated: August 5, 2014
Last verified: August 2014

November 20, 2011
August 5, 2014
November 2011
June 2017   (final data collection date for primary outcome measure)
Comparison of DFS in vaccine treated patients and control patients [ Time Frame: 36 months ] [ Designated as safety issue: No ]
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.
Comparison of disease-free survival in vaccine treated patients and control patients [ Time Frame: 36 months ] [ Designated as safety issue: No ]
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.
Complete list of historical versions of study NCT01479244 on ClinicalTrials.gov Archive Site
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 ] [ Designated as safety issue: Yes ]

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)
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 ] [ Designated as safety issue: Yes ]

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)
Not Provided
Not Provided
 
Efficacy and Safety Study of NeuVax™ (Nelipepimut-S or E75) Vaccine to Prevent Breast Cancer Recurrence
PRESENT: Prevention of Recurrence in Early-Stage, Node-Positive Breast Cancer With Low to Intermediate HER2 Expressions With NeuVax™Treatment

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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
HER2 Low to Intermediate Breast Cancer
  • 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®
  • 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

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
700
June 2024
June 2017   (final data collection date for primary outcome measure)

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
Female
18 Years and older
No
Contact: Gavin Choy 855-855-4253 ext 113 gchoy@galenabiopharma.com
Contact: Lacey Chance 303-722-7768 lchance@galenabiopharma.com
United States,   Bulgaria,   Canada,   Czech Republic,   France,   Germany,   Hungary,   Israel,   Poland,   Romania,   Russian Federation,   Ukraine,   United Kingdom
 
NCT01479244
NeuVax™ PH3-01, BB-IND 009187, 2011-005219-98
Yes
Galena Biopharma, Inc.
Galena Biopharma, Inc.
Not Provided
Principal Investigator: Elizabeth A Mittendorf, MD,FACS M.D. Anderson Cancer Center
Galena Biopharma, Inc.
August 2014

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