Combination Immunotherapy With Herceptin and the HER2 Vaccine NeuVax
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT01570036 |
Recruitment Status :
Completed
First Posted : April 4, 2012
Results First Posted : December 2, 2020
Last Update Posted : December 2, 2020
|
- Study Details
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Breast Cancer | Drug: Herceptin Drug: NeuVax vaccine Drug: GM-CSF | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 275 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Single (Participant) |
Primary Purpose: | Prevention |
Official Title: | Combination Immunotherapy With Herceptin and the HER2 Vaccine E75 in Low and Intermediate HER2-expressing Breast Cancer Patients to Prevent Recurrence |
Actual Study Start Date : | May 21, 2013 |
Actual Primary Completion Date : | September 28, 2018 |
Actual Study Completion Date : | September 28, 2018 |
Arm | Intervention/treatment |
---|---|
Experimental: Herceptin + NeuVax vaccine
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.
|
Drug: Herceptin
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.
Other Name: Trastuzumab Drug: NeuVax vaccine 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.
Other Names:
Drug: GM-CSF 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.
Other Name: Sargramostim |
Active Comparator: Herceptin + GM-CSF only
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.
|
Drug: Herceptin
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.
Other Name: Trastuzumab Drug: GM-CSF 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.
Other Name: Sargramostim |
- 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.
- Percent Ejection Fraction - A Measure of Cardiac Toxicity [ Time Frame: 24 months ]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.
- Local and Systemic Toxicities [ Time Frame: Duration of vaccine or inoculation series and booster series, an average of 30 months. ]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.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | Female |
Accepts Healthy Volunteers: | No |
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)
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): NCT01570036
Principal Investigator: | COL (ret.) George E. Peoples, MD, FACS | Cancer Insight, LLC | |
Study Director: | COL (ret.) George E. Peoples, MD, FACS | Cancer Insight, LLC |
Documents provided by George E. Peoples, Cancer Insight, LLC:
Responsible Party: | George E. Peoples, President and CEO, Cancer Insight, LLC, Cancer Insight, LLC |
ClinicalTrials.gov Identifier: | NCT01570036 |
Other Study ID Numbers: |
368255 1137008 / 20130058 ( Other Identifier: Western Institutional Review Board ) |
First Posted: | April 4, 2012 Key Record Dates |
Results First Posted: | December 2, 2020 |
Last Update Posted: | December 2, 2020 |
Last Verified: | November 2020 |
stage I breast cancer stage II breast cancer stage IIIA breast cancer |
stage IIIB breast cancer stage IIIC breast cancer male breast cancer |
Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Trastuzumab |
Molgramostim Sargramostim Antineoplastic Agents, Immunological Antineoplastic Agents Immunologic Factors Physiological Effects of Drugs |