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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.

Study Description
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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.

Condition or disease Intervention/treatment Phase
Breast Cancer With Low to Intermediate HER2 Expression Biological: NeuVax™ vaccine Biological: Leukine® (sargramostim, GM-CSF) and water for injection Phase 3

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 758 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: PRESENT: Prevention of Recurrence in Early-Stage, Node-Positive Breast Cancer With Low to Intermediate HER2 Expressions With NeuVax™Treatment
Study Start Date : November 2011
Actual Primary Completion Date : September 21, 2016
Actual Study Completion Date : September 21, 2016

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: NeuVax™
NeuVax™ in WFI solution with Leukine®
 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
Active Comparator: Leukine®
Leukine® with WFI
 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®


Outcome Measures
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Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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)


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01479244


Locations
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Sponsors and Collaborators
Galena Biopharma, Inc.
Investigators
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Principal Investigator: Elizabeth A Mittendorf, MD,FACS M.D. Anderson Cancer Center
More Information
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Additional Information:

Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Galena Biopharma, Inc.
ClinicalTrials.gov Identifier: NCT01479244    
Other Study ID Numbers: NeuVax™ PH3-01, BB-IND 009187
2011-005219-98 ( EudraCT Number )
First Posted: November 24, 2011    Key Record Dates
Last Update Posted: February 27, 2017
Last Verified: February 2017
Keywords provided by Galena Biopharma, Inc.:
HER2
low or intermediate
breast cancer
node-positive tumors
Additional relevant MeSH terms:
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Breast Neoplasms
Recurrence
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Disease Attributes
 Pathologic Processes
Molgramostim
Sargramostim
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents