Combination Immunotherapy With Herceptin and the HER2 Vaccine NeuVax
2 other identifiers
interventional
275
1 country
29
Brief Summary
The study will be a multi-center, prospective, randomized, single-blinded, placebo-controlled Phase II trial of Herceptin + NeuVax(TM) vaccine (E75 peptide/granulocyte macrophage-colony stimulating factor) (GM-CSF) versus Herceptin + GM-CSF alone. The target study population is node-positive (NP) (or node-negative \[NN\] if negative for both ER and PR) breast cancer patients with HER2 1+ and 2+ expressing tumors who are disease-free after standard of care therapy. Disease-free subjects after standard of care multi-modality therapy will be screened and HLA-typed. E75 is a CD8-eliciting peptide vaccine that was restricted to HLA-A2+ or HLA-A3+ patients (approximately two-thirds of the US population), and has been extended to HLA-A24+ and HLA-A26+ as well.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2 breast-cancer
Started May 2013
Typical duration for phase_2 breast-cancer
29 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 25, 2012
CompletedFirst Posted
Study publicly available on registry
April 4, 2012
CompletedStudy Start
First participant enrolled
May 21, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 28, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
September 28, 2018
CompletedResults Posted
Study results publicly available
December 2, 2020
CompletedDecember 2, 2020
November 1, 2020
5.4 years
March 25, 2012
June 17, 2019
November 9, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Disease-free Survival (DFS)
Disease-free survival (DFS) for all patients regardless of randomization will be determined by patients' own physicians at the individual study sites during routine follow-up screening. This will occur every three months for the first 24 months after completion of primary therapies and every six months thereafter with clinical exam, and laboratory and radiographic surveillance. The primary objective of the study is disease-free survival (DFS) at 24 months.
Disease-free survival at 24 months
Disease-free Survival (DFS)
Disease-free survival (DFS) for all patients regardless of randomization will be determined by patients' own physicians at the individual study sites during routine follow-up screening. This will occur at months 30 and 36 after completion of primary therapies with clinical exam, and laboratory and radiographic surveillance. The secondary objective of the study is disease-free survival (DFS) at 36 months.
Disease-free survival up to 36 months
Secondary Outcomes (2)
Percent Ejection Fraction - A Measure of Cardiac Toxicity
24 months
Local and Systemic Toxicities
Duration of vaccine or inoculation series and booster series, an average of 30 months.
Study Arms (2)
Herceptin + NeuVax vaccine
EXPERIMENTALPatients randomized to this arm will receive Herceptin every 3 weeks as monotherapy for 1 year; the first Herceptin infusion will be given no sooner than 3 weeks and no later than 12 weeks after completion of standard of care chemotherapy/radiotherapy. Herceptin will be dosed at the recommended initial loading dose of 8 mg/kg and at recommended maintenance doses of 6 mg/kg q3wk. Patients will receive vaccinations of NeuVax vaccine administered intradermally every 3 weeks for 6 total vaccinations, 30-120 minutes after completion of Herceptin infusion. The NeuVax vaccine series will begin immediately after completion of the third Herceptin infusion, but may be delayed to the fourth or fifth Herceptin infusion with prior approval from the PI. Patients will be blinded regarding assigned arm. After completion of primary vaccine series, patients will receive 4 NeuVax vaccine booster inoculations to be administered every 6 months x 4 for total treatment duration of 30 months.
Herceptin + GM-CSF only
ACTIVE COMPARATORPatients randomized to this arm will receive Herceptin every 3 weeks as monotherapy for 1 year. The first Herceptin infusion will be given no sooner than 3 weeks and no later than 12 weeks after completion of standard of care chemotherapy/radiotherapy. Herceptin will be dosed at the recommended initial loading dose of 8 mg/kg and at recommended maintenance doses of 6 mg/kg q3wk. Patients will receive inoculations of GM-CSF only (250mcg) administered intradermally every 3 weeks for 6 total inoculations, 30-120 minutes after completion of Herceptin infusion. The GM-CSF only inoculation series will begin immediately after completion of the third Herceptin infusion. Patients will be blinded as to whether they are receiving NeuVax vaccine or GM-CSF only. After completion of six-inoculation primary vaccine series, patients will then receive a total of four GM-CSF only booster inoculations to be administered at 12, 18, 24, and 30 months from the date of the first Herceptin infusion.
Interventions
Herceptin will be administered to patients every three weeks as monotherapy for one year, to be given upon completion of standard of care chemotherapy/radiotherapy. The first Herceptin infusion will be given no sooner than three weeks and no later than 12 weeks after completion of chemotherapy/radiotherapy. Herceptin will be dosed at the recommended initial loading dose of 8 mg/kg and at recommended maintenance doses of 6 mg/kg q3wk.
At the time of vaccine administration, a frozen solution of E75 acetate (1.5mg/ml) is thawed and 1000mcg E75 peptide mixed thoroughly with 250mcg GM-CSF. This constitutes the NeuVax vaccine. For patients randomized to the Herceptin + NeuVax vaccine arm, they will commence Herceptin monotherapy and then will begin the NeuVax vaccine series immediately after completion of the third Herceptin infusion. The vaccine series consists of NeuVax vaccine administered intradermally every three weeks for six total vaccinations, 30-120 minutes after completion of Herceptin infusion.
For patients randomized to the Herceptin + GM-CSF only arm, they will commence Herceptin monotherapy and then will begin the GM-CSF inoculation series immediately after completion of the third Herceptin infusion. The GM-CSF inoculation series consists of 250mcg GM-CSF administered intradermally every three weeks for six total vaccinations, 30-120 minutes after completion of Herceptin infusion.
Eligibility Criteria
You may not qualify if:
- Patients will be excluded from the study based on the following criteria:
- Node-negative breast cancer (AJCC N0 or N0(i+)) unless negative for both estrogen (ER) and progesterone (PR) receptors and has received chemotherapy as standard of care
- Clinical or radiographic evidence of distant or residual breast cancer
- HER2 negative (IHC 0) or HER2 3+ or FISHDual-ISH amplified (FISH \>2.0); Dual-ISH \>2.0
- HLA-A2, A3, A24, A26 negative
- History of prior Herceptin therapy
- NYHA stage 3 or 4 cardiac disease
- LVEF \<50%, or less than the normal limits of the institution's specific testing (MUGA or Echo)
- Immune deficiency disease or HIV, HBV, HCV
- Receiving immunosuppressive therapy including chemotherapy, chronic steroids, methotrexate, or other known immunosuppressive agents
- ECOG ≥2
- Tbili \>1.8, creatinine\>2, hemoglobin\<10, platelets\<50,000, WBC\<2,000
- Pregnancy (assessed by urine HCG)
- Breast feeding
- Any active autoimmune disease requiring treatment, with the exception of vitiligo
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- George E. Peopleslead
- Genentech, Inc.collaborator
- Sellas Life Sciences Groupcollaborator
Study Sites (29)
Samuel Oschin Comprehensive Cancer Institute - Cedars Sinai Medical Center
Beverly Hills, California, 90211, United States
Sarcoma Oncology Research Center, LLC
Santa Monica, California, 90403, United States
St. Joseph Heritage Healthcare
Santa Rosa, California, 95403, United States
Sibley Memorial Hospital
Washington D.C., District of Columbia, 20016, United States
Katzen Cancer Research Center, George Washington University
Washington D.C., District of Columbia, 20037, United States
University of Miami
Deerfield Beach, Florida, 33442, United States
University of Miami
Kendall, Florida, 33176, United States
University of Miami
Miami, Florida, 33136, United States
Florida Cancer Research Institute
Plantation, Florida, 33324, United States
University of Miami
Plantation, Florida, 33324, United States
H. Lee Moffitt Cancer Center & Research Institute, Inc
Tampa, Florida, 33612, United States
University of Hawaii Cancer Center
Honolulu, Hawaii, 96813, United States
Franciscan Health Indianapolis
Indianapolis, Indiana, 46237, United States
Memorial Hospital of South Bend
South Bend, Indiana, 46601, United States
Cancer Center of Kansas
Wichita, Kansas, 67212, United States
Medstar Health - Union Memorial Hospital
Baltimore, Maryland, 21218-2895, United States
Medstar Health - Weinberg Cancer Institute at Franklin Square
Baltimore, Maryland, 21237, United States
MedStar Health - Good Samaritan Hospital
Baltimore, Maryland, 21239, United States
The Valley Hospital
Paramus, New Jersey, 07652, United States
Tisch Cancer Institute/Icahn School of Medicine at Mount Sinai
New York, New York, 10029, United States
North Shore Hematology Oncology Associates
The Bronx, New York, 10469, United States
Legacy Health, Legacy Good Samaritan Medical Center
Portland, Oregon, 97210, United States
Thomas Jefferson University - Kimmel Cancer Center
Philadelphia, Pennsylvania, 19107, United States
University of Texas M.D. Anderson Cancer Center
Houston, Texas, 77030, United States
Texas Oncology (Cancer Care Centers of South Texas)
San Antonio, Texas, 78217, United States
Virginia Cancer Specialists
Fairfax, Virginia, 22031, United States
Providence Regional Medical Center
Everett, Washington, 98201, United States
Swedish Cancer Institute
Seattle, Washington, 98104, United States
Columbia St. Mary's
Milwaukee, Wisconsin, 53211, United States
Related Publications (1)
Clifton GT, Hale D, Vreeland TJ, Hickerson AT, Litton JK, Alatrash G, Murthy RK, Qiao N, Philips AV, Lukas JJ, Holmes JP, Peoples GE, Mittendorf EA. Results of a Randomized Phase IIb Trial of Nelipepimut-S + Trastuzumab versus Trastuzumab to Prevent Recurrences in Patients with High-Risk HER2 Low-Expressing Breast Cancer. Clin Cancer Res. 2020 Jun 1;26(11):2515-2523. doi: 10.1158/1078-0432.CCR-19-2741. Epub 2020 Feb 18.
PMID: 32071118DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Program Director, Karen Arrington, RN, BSN
- Organization
- Cancer Insight
Study Officials
- PRINCIPAL INVESTIGATOR
COL (ret.) George E. Peoples, MD, FACS
Cancer Insight, LLC
- STUDY DIRECTOR
COL (ret.) George E. Peoples, MD, FACS
Cancer Insight, LLC
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- PARTICIPANT
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- President and CEO, Cancer Insight, LLC
Study Record Dates
First Submitted
March 25, 2012
First Posted
April 4, 2012
Study Start
May 21, 2013
Primary Completion
September 28, 2018
Study Completion
September 28, 2018
Last Updated
December 2, 2020
Results First Posted
December 2, 2020
Record last verified: 2020-11