Breast CancerPhase 2NCT01570036
Combination Immunotherapy With Herceptin and the HER2 Vaccine NeuVax
A Phase 2 study testing Herceptin, NeuVax vaccine and GM-CSF in people with Breast Cancer, run by George E. Peoples at 29 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Herceptin, NeuVax vaccine and GM-CSF
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 275 participants
- Where
- 29 sitesUnited States
- Study dates
- 21 May 2013to 28 Sep 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Patients will be included in the study based on the following criteria:
- Women 18 years or older
- Node-positive breast cancer (AJCC N1, N2, or N3)
- Node-negative breast cancer if negative for both estrogen (ER) and progesterone (PR) receptors and have received chemotherapy as standard of care
- Clinically cancer-free (no evidence of disease) after standard of care therapy (surgery, chemotherapy, radiation therapy as directed by NCCN guidelines). Hormonal therapy will continue per standard of care. Neoadjuvant chemotherapy is allowed.
- Recovery from any toxicity(ies) associated with prior adjuvant therapy.
- HER2 expression of 1+ or 2+ by IHC. FISH or Dual-ISH testing must be performed on IHC 2+ tumors and shown to be non-amplified by FISH (≤2.0) or by Dual-ISH (≤2.0).
- HLA-A2, A3, A24, or A26 positive
- LVEF >50%, or an LVEF within the normal limits of the institution's specific testing (MUGA or Echo)
- ECOG 0,1
- Signed informed consent
- Adequate birth control (abstinence, hysterectomy, bilateral oophorectomy, bilateral tubal ligation, oral contraception, IUD, or use of condoms or diaphragms)
- Must start study treatment (receive first Herceptin infusion) 15between 3-12 weeks from completion of standard of care therapy.
4.1.3 Exclusion Criteria
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
- Active pulmonary disease requiring medication to include multiple inhalers
- Involved in other experimental protocols (except with permission of the other study PI)
Trial locations and contacts
29 sites in 1 country.
29 sites in 1 country
United States29 sites
Medstar Health - Union Memorial Hospital
Baltimore, Maryland, 21218-2895
Medstar Health - Weinberg Cancer Institute at Franklin Square
Baltimore, Maryland, 21237
MedStar Health - Good Samaritan Hospital
Baltimore, Maryland, 21239
Samuel Oschin Comprehensive Cancer Institute - Cedars Sinai Medical Center
Beverly Hills, California, 90211
University of Miami
Deerfield Beach, Florida, 33442
Providence Regional Medical Center
Everett, Washington, 98201
Virginia Cancer Specialists
Fairfax, Virginia, 22031
University of Hawaii Cancer Center
Honolulu, Hawaii, 96813
University of Texas M.D. Anderson Cancer Center
Houston, Texas, 77030
Franciscan Health Indianapolis
Indianapolis, Indiana, 46237
University of Miami
Kendall, Florida, 33176
University of Miami
Miami, Florida, 33136
Columbia St. Mary's
Milwaukee, Wisconsin, 53211
Tisch Cancer Institute/Icahn School of Medicine at Mount Sinai
New York, New York, 10029
The Valley Hospital
Paramus, New Jersey, 07652
Thomas Jefferson University - Kimmel Cancer Center
Philadelphia, Pennsylvania, 19107
Florida Cancer Research Institute
Plantation, Florida, 33324
University of Miami
Plantation, Florida, 33324
Legacy Health, Legacy Good Samaritan Medical Center
Portland, Oregon, 97210
Texas Oncology (Cancer Care Centers of South Texas)
San Antonio, Texas, 78217
Sarcoma Oncology Research Center, LLC
Santa Monica, California, 90403
St. Joseph Heritage Healthcare
Santa Rosa, California, 95403
Swedish Cancer Institute
Seattle, Washington, 98104
Memorial Hospital of South Bend
South Bend, Indiana, 46601
H. Lee Moffitt Cancer Center & Research Institute, Inc
Tampa, Florida, 33612
North Shore Hematology Oncology Associates
The Bronx, New York, 10469
Sibley Memorial Hospital
Washington D.C., District of Columbia, 20016
Katzen Cancer Research Center, George Washington University
Washington D.C., District of Columbia, 20037
Cancer Center of Kansas
Wichita, Kansas, 67212
About this study
Official title: Combination Immunotherapy With Herceptin and the HER2 Vaccine E75 in Low and Intermediate HER2-expressing Breast Cancer Patients to Prevent Recurrence
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.
Read the detailed description
In this study, the investigators intend to assess the ability of the combination of Herceptin and NeuVax vaccine (HER2 protein E75 peptide administered with the immunoadjuvant GM-CSF) given in the adjuvant setting to prevent recurrences in NP (or NN if negative for both estrogen (ER) and progesterone (PR) receptors) breast cancer patients with tumors that express low (1+) or intermediate (2+) levels of HER2. Enrolled patients will be randomized to receive Herceptin and NeuVax vaccine or Herceptin with GM-CSF alone (no NeuVax vaccine). The safety of the combination therapy will be documented, specifically to ensure that no additive cardiac toxicity results from combination HER2-directed therapy. Efficacy will be documented by comparing the DFS and immunological responses between treatment groups.
The primary efficacy endpoint is to compare DFS at 24 months between treatment groups. The primary safety issue is to prove there is no additive cardiac toxicity with combination HER2-directed therapy. A secondary endpoint of the trial is to compare DFS at 36 months. Immunologic responses to the vaccine will also be documented and correlated to clinical benefit.
The study will be a multi-center, prospective, randomized, single-blinded, placebo-controlled Phase II trial of Herceptin + NeuVax vaccine versus Herceptin + GM-CSF alone. The target study population is NP (or 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 is 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.
HLA-A2+/A3+/A24+/or A26+ patients who meet all other eligibility criteria will be randomized to receive Herceptin + NeuVax vaccine or Herceptin + GM-CSF alone. For both groups, Herceptin will be given every three weeks as monotherapy for one year, to be given upon completion of standard of care chemotherapy/radiotherapy. The first Herceptin infusion must 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. Herceptin will be administered as described in Section 4.3. Patients randomized to the NeuVax vaccine arm will receive vaccinations of E75 peptide (1000 mcg) and GM-CSF (250 mcg) administered intradermally every three weeks for six total vaccinations, 30-120 minutes after completion of Herceptin infusion. The NeuVax vaccine series will begin immediately after completion of the third Herceptin infusion. In extenuating circumstances, the first vaccination may be delayed to the fourth or fifth Herceptin infusion with prior approval from the Principal Investigator. Those patients randomized to the GM-CSF alone arm will receive vaccinations of GM-CSF (250 mcg) administered in an identical manner to those receiving NeuVax vaccine. Patients will be blinded as to whether they are receiving NeuVax vaccine or GM-CSF alone.
Upon completion of the vaccination series, booster inoculations (same dose and route) will be administered every six months x4 for total combination (Herceptin and vaccine) treatment duration of 30 months. The first booster inoculation will occur with the final Herceptin infusion, with subsequent boosters timed every six months from the first booster. Booster inoculations will occur for patients randomized to receive E75/GM-CSF as well as patients randomized to receive GM-CSF alone, and will consist of the same treatment drugs and dosing (i.e. E75/GM-CSF patients will be boosted with E75/GM-CSF while GM-CSF alone patients will be boosted with GM-CSF alone). Patient blinding will be maintained throughout the study.
Subjects will be followed for safety issues, immunologic response and clinical recurrence. Patients will be monitored 48-72 hours after each inoculation for reaction to the inoculation as well as documentation of any adverse effects experienced. Immunologic response will be documented with both in vitro phenotypic and functional assays as well as in vivo delayed type hypersensitivity (DTH) reactions. All patients will be followed for a total of 36 months to document disease-free status.
The investigators plan to enroll 300 patients (150 in each treatment arm) at a planned accrual rate of 12 patients per month (approximately one per study site per month). With accrual beginning in April, 2013, enrollment of the last patient would be expected in August 2017 followed by a three-year follow-up period. The duration of the trial is expected to be seven years.
- Conditions
- Breast Cancer
- Being tested
- Herceptin, NeuVax vaccine, GM-CSF
- Keywords
- stage I breast cancer, stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, male breast cancer
- Medical subject headings
- Breast Neoplasms, Breast Neoplasms, Male
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HerceptinDrug
Also called Trastuzumab
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.
NeuVax vaccineDrug
Also called E75 peptide (KIFGSLAFL, HER2/neu, 369-377), GM-CSF (sargramostim)
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.
GM-CSFDrug
Also called Sargramostim
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.
| Study group | Role | What they receive |
|---|---|---|
| Herceptin + NeuVax vaccine | Experimental | Patients 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. Receives: Drug: Herceptin; Drug: NeuVax vaccine; Drug: GM-CSF |
| Herceptin + GM-CSF only | Active comparator | Patients 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. Receives: Drug: Herceptin; Drug: GM-CSF |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Disease-free survival up to 36 months
Secondary outcomes (2)
Percent Ejection Fraction - A Measure of Cardiac Toxicity
Each patient, regardless of randomization, will undergo cardiac assessment (ejection fraction) of Multiple Gated Acquisition scan (MUGA) preferred, echocardiogram (ECHO) allowed, consistency required) at baseline, 3 months, 6 months, 12 months, and 24 months. Cardiac assessment will continue every six months if a patient experiences a greater than 10% reduction from baseline for the duration of the trial or until resolution.
Measured: 24 months
Local and Systemic Toxicities
Standard local and systemic toxicities will be collected and graded per the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03 toxicity scale. For both the regular and booster inoculations, patients will be monitored closely for one hour after inoculation with questioning, serial exams and vital signs every 15 minutes to observe for a hypersensitivity reaction. Patients will also return to the clinic 48-72 hours after each inoculation for questioning regarding systemic toxicity and to examine and measure the local reaction at the inoculation sites. Reported are the maximum related and graded adverse events per patient.
Measured: Duration of vaccine or inoculation series and booster series, an average of 30 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2012 (estimated)
- Study start21 May 2013
- Primary completion28 Sep 2018
- Study completion28 Sep 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 275 participants (actual)
Sponsor and investigators
- Lead sponsor
- George E. Peoples
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Genentech, Inc., Sellas Life Sciences Group
- Responsible party
- Sponsor-investigator, George E. Peoples, Cancer Insight, LLC
- Investigators
- COL (ret.) George E. Peoples, MD, FACS, Principal investigator, Cancer Insight, LLCCOL (ret.) George E. Peoples, MD, FACS, Study director, Cancer Insight, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01570036
- Sponsor's protocol ID
- 368255
- Other IDs
- 1137008 / 20130058
- Status last verified
- Nov 2020
- First submitted
- 25 Mar 2012
- Last updated
- 2 Dec 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 32071118
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combination Immunotherapy With Herceptin and the HER2 Vaccine E75 in Low and Intermediate HER2-expressing Breast Cancer Patients to Prevent Recurrence
- ClinicalTrials.gov ID
- NCT01570036
- Acronym / sponsor ID
- 368255
- Conditions
- Breast Cancer
- Keywords
- stage I breast cancer, stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, male breast cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 275 participants (actual)
- Lead sponsor
- George E. PeoplesIndustry (pharma, biotech, devices)
- Collaborators
- Genentech, Inc., Sellas Life Sciences Group
- Study start
- 21 May 2013 (actual)
- Primary completion
- 28 Sep 2018 (actual)
- Study completion
- 28 Sep 2018 (actual)
- First posted
- 4 Apr 2012 (estimated)
- Results
- Posted 2 Dec 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
In this study, the investigators intend to assess the ability of the combination of Herceptin and NeuVax vaccine (HER2 protein E75 peptide administered with the immunoadjuvant GM-CSF) given in the adjuvant setting to prevent recurrences in NP (or NN if negative for both estrogen (ER) and progesterone (PR) receptors) breast cancer patients with tumors that express low (1+) or intermediate (2+) levels of HER2. Enrolled patients will be randomized to receive Herceptin and NeuVax vaccine or Herceptin with GM-CSF alone (no NeuVax vaccine). The safety of the combination therapy will be documented, specifically to ensure that no additive cardiac toxicity results from combination HER2-directed therapy. Efficacy will be documented by comparing the DFS and immunological responses between treatment groups.
The primary efficacy endpoint is to compare DFS at 24 months between treatment groups. The primary safety issue is to prove there is no additive cardiac toxicity with combination HER2-directed therapy. A secondary endpoint of the trial is to compare DFS at 36 months. Immunologic responses to the vaccine will also be documented and correlated to clinical benefit.
The study will be a multi-center, prospective, randomized, single-blinded, placebo-controlled Phase II trial of Herceptin + NeuVax vaccine versus Herceptin + GM-CSF alone. The target study population is NP (or 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 is 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.
HLA-A2+/A3+/A24+/or A26+ patients who meet all other eligibility criteria will be randomized to receive Herceptin + NeuVax vaccine or Herceptin + GM-CSF alone. For both groups, Herceptin will be given every three weeks as monotherapy for one year, to be given upon completion of standard of care chemotherapy/radiotherapy. The first Herceptin infusion must 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. Herceptin will be administered as described in Section 4.3. Patients randomized to the NeuVax vaccine arm will receive vaccinations of E75 peptide (1000 mcg) and GM-CSF (250 mcg) administered intradermally every three weeks for six total vaccinations, 30-120 minutes after completion of Herceptin infusion. The NeuVax vaccine series will begin immediately after completion of the third Herceptin infusion. In extenuating circumstances, the first vaccination may be delayed to the fourth or fifth Herceptin infusion with prior approval from the Principal Investigator. Those patients randomized to the GM-CSF alone arm will receive vaccinations of GM-CSF (250 mcg) administered in an identical manner to those receiving NeuVax vaccine. Patients will be blinded as to whether they are receiving NeuVax vaccine or GM-CSF alone.
Upon completion of the vaccination series, booster inoculations (same dose and route) will be administered every six months x4 for total combination (Herceptin and vaccine) treatment duration of 30 months. The first booster inoculation will occur with the final Herceptin infusion, with subsequent boosters timed every six months from the first booster. Booster inoculations will occur for patients randomized to receive E75/GM-CSF as well as patients randomized to receive GM-CSF alone, and will consist of the same treatment drugs and dosing (i.e. E75/GM-CSF patients will be boosted with E75/GM-CSF while GM-CSF alone patients will be boosted with GM-CSF alone). Patient blinding will be maintained throughout the study.
Subjects will be followed for safety issues, immunologic response and clinical recurrence. Patients will be monitored 48-72 hours after each inoculation for reaction to the inoculation as well as documentation of any adverse effects experienced. Immunologic response will be documented with both in vitro phenotypic and functional assays as well as in vivo delayed type hypersensitivity (DTH) reactions. All patients will be followed for a total of 36 months to document disease-free status.
The investigators plan to enroll 300 patients (150 in each treatment arm) at a planned accrual rate of 12 patients per month (approximately one per study site per month). With accrual beginning in April, 2013, enrollment of the last patient would be expected in August 2017 followed by a three-year follow-up period. The duration of the trial is expected to be seven years.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Herceptin + NeuVax vaccine | Experimental | Drug: Herceptin, Drug: NeuVax vaccine, Drug: GM-CSFPatients 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 comparator | Drug: Herceptin, Drug: GM-CSFPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HerceptinAlso: TrastuzumabHerceptin 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. | Drug | Herceptin + GM-CSF only, Herceptin + NeuVax vaccine |
| NeuVax vaccineAlso: E75 peptide (KIFGSLAFL, HER2/neu, 369-377), GM-CSF (sargramostim)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. | Drug | Herceptin + NeuVax vaccine |
| GM-CSFAlso: SargramostimFor 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. | Drug | Herceptin + GM-CSF only, Herceptin + NeuVax vaccine |
Primary outcome
Disease-free Survival (DFS)
Time frame: Disease-free survival at 24 months
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 (DFS)
Time frame: Disease-free survival up to 36 months
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.
2 secondary outcomes
Percent Ejection Fraction - A Measure of Cardiac Toxicity
Time frame: 24 months
Local and Systemic Toxicities
Time frame: Duration of vaccine or inoculation series and booster series, an average of 30 months.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32071118Clifton 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
COL (ret.) George E. Peoples, MD, FACS principal investigator
Cancer Insight, LLC
COL (ret.) George E. Peoples, MD, FACS study director
Cancer Insight, LLC
29 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Herceptin, NeuVax vaccine and GM-CSF in people with Breast Cancer, run by George E. Peoples at 29 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 29 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disease-free Survival (DFS) (time frame: Disease-free survival at 24 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01570036, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Dec 2020.