A Phase 2 interventional study of NeuVax vaccine and Trastuzumab in Breast Cancer, sponsored by Cancer Insight, LLC. Completed at 24 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-12-12.
Sponsored by Cancer Insight, LLC · Phase 2, Interventional, and Prevention
This will be a multi-center, prospective, randomized, single-blinded, placebo-controlled phase II trial of trastuzumab + nelipepimut-S/GM-CSF versus trastuzumab + GM-CSF alone. Our target study population is high-risk HER2-positive breast cancer patients. High-risk HER2-positive breast cancer patients are defined as:
Those with HER2-positive breast cancer, regardless of hormone receptor status, who receive neoadjuvant therapy with an approved regimen that includes trastuzumab and at least four cycles (12 weeks) of taxane-containing chemotherapy, and fail to achieve a pCR.
Those with HER2-positive breast cancer, regardless of hormone receptor status, who undergo surgery as a first intervention and are found to have ≥ 4 positive lymph nodes.
Those with HER2-positive, hormone receptor negative breast cancer who undergo surgery as a first intervention and are found to have 1-3 positive lymph nodes.
Disease-free subjects after standard of care multi-modality therapy will be screened and HLA-typed.
In this study, the investigators intend to assess the ability of the combination of trastuzumab and the HER2 vaccine nelipepimut-S (administered with the immunoadjuvant GM-CSF) given in the adjuvant setting to prevent recurrences in patients with high-risk HER2-positive breast cancer. High-risk is defined as those patients that do not achieve a pCR after neoadjuvant therapy with an approved regimen that includes trastuzumab and at least four cycles (12 weeks) of taxane-containing chemotherapy or those who undergo upfront surgery and are found to have greater than or equal to four positive lymph nodes regardless of hormone receptor status or 1-3 positive lymph nodes and are hormone receptor negative.
Following surgery, patients will be screened and HLA-typed (consent #1). Nelipepimut-S is a CD8-eliciting peptide vaccine that is restricted to HLA-2+ or HLA-A3+ or HLA-A24+ or HLA-A26+ patients (approximately 80% of the US population). HLA-A2+/A3+/A24+/orA26+ patients who meet all other eligibility criteria will be randomized to receive trastuzumab + nelipepimut-S/GM-CSF or trastuzumab + GM-CSF alone (consent #2). The trastuzumab will be administered to all patients consistent with current standard of care. Patients randomized to the nelipepimut-S/GM-CSF arm will receive vaccinations of nelipepimut-S (1000 mcg) and GM-CSF (250 mcg) administered intradermally every three weeks for six total vaccinations, 30-120 minutes after completion of trastuzumab infusion. The first vaccination will be given with the third dose of maintenance trastuzumab administered as monotherapy optimally, but may be given with later maintenance doses of trastuzumab, provided there are at least six remaining doses of trastuzumab to overlap with the primary vaccine series. Patients randomized to the GM-CSF alone arm will receive inoculations of GM-CSF (250 mcg) administered in an identical manner to those receiving nelipepimut-S/GM-CSF. Patients will be blinded as to whether they are receiving nelipepimut-S/GM-CSF or GM-CSF alone.
Upon completion of the primary vaccination/inoculation series, booster inoculations (same dose and route) will be administered every six months x 4. The first booster inoculation will occur 6 months ± 2 weeks after the completion of the PVS, with subsequent boosters timed every six months + 2 weeks. Boosters will therefore occur at the following time points after completion of the PVS: 6 months ± 2 weeks, 12 months ± 2 weeks, 18 months ± 2 weeks, 24 months ± 2 weeks. Booster inoculations will occur for patients randomized to receive nelipepimut-S/GM-CSF as well as patients randomized to receive GM-CSF alone, and will consist of the same treatment drugs and dosing (i.e., nelipepimut-S/GM-CSF patients will be boosted with nelipepimut-S/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 monitored primarily by in vivo delayed type hypersensitivity (DTH) reactions but also may be documented by other immunologic assays. All patients will be followed for a total of 36 months from the time of initiation of trastuzumab maintenance therapy to document disease-free status.
12,543 studies on the registry are indexed under Breast Neoplasms; 2,892 are open to participants now.
This study's enrollment of 100 is above the median of 72 across 9,302 interventional studies indexed under Breast Neoplasms.
Browse Breast Neoplasms studies →Cancer Insight, LLC is the lead sponsor of 3 studies on the registry; none are open to participants now.
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Completed appropriate surgical therapy to include:
For patients undergoing total mastectomy surgery as a first intervention, post-mastectomy radiation to the chest wall, infraclavicular and supraclavicular areas is required for patients with ≥ 4 positive lymph nodes. Radiation to the internal mammary lymph nodes is not required per protocol but is allowed at the discretion of the patient's treating radiation oncologist. For patients with 1-3 positive lymph nodes, post-mastectomy radiation to the chest wall, infraclavicular, supraclavicular, and internal mammary areas is not required per protocol but is allowed at the discretion of the patient's treating radiation oncologist.
For patient's undergoing BCS after neoadjuvant chemotherapy, whole breast irradiation with or without a boost is required. For patients with clinical N2 or N3 disease or with ≥ 4 positive lymph nodes identified pathologically at the time of surgery, radiation to the infraclavicular and supraclavicular areas is required. Radiation to the internal mammary lymph nodes is not required per protocol but is allowed at the discretion of the patient's treating radiation oncologist. For patients with 0-3 positive lymph nodes identified pathologically, radiation to the infraclavicular, supraclavicular and internal mammary areas is not required per protocol but is allowed at the discretion of the patient's treating radiation oncologist.
Adequate organ function as determined by the following laboratory values:
Exclusion criteria:
Patients randomized to this arm will receive vaccinations of nelipepimut-S (1000 μg) and GM-CSF (250 μg) (NeuVax vaccine) administered intradermally every three weeks for six total vaccinations, 30-120 minutes after completion of trastuzumab infusion. The first vaccination will be given with the third dose of maintenance trastuzumab administered as monotherapy optimally, but may be given with later maintenance doses of trastuzumab, provided there are at least six remaining doses of trastuzumbab to overlap with the PVS. Upon completion of the primary vaccination series (PVS), booster inoculations (same dose and route) will be administered every six months x 4. The first booster inoculation will occur 6 months ± 2 weeks after the completion of the PVS, with subsequent boosters timed every six months + 2 weeks. Boosters will therefore occur at the following time points after completion of the PVS: 6 months ± 2 weeks, 12 months ± 2 weeks, 18 months ± 2 weeks and 24 months ± 2 weeks.
Biological: NeuVax vaccine · Drug: Trastuzumab · Drug: GM-CSF
Patients randomized to this arm will receive inoculations of GM-CSF (250 μg) administered in an identical manner to those receiving nelipepimut-S/GM-CSF (NeuVax). Patients will be blinded as to whether they are receiving nelipepimut-S/GM-CSF or GM-CSF alone. Upon completion of the primary vaccination series (PVS), booster inoculations (same dose and route) will be administered every six months x 4. The first booster inoculation will occur 6 months ± 2 weeks after the completion of the PVS, with subsequent boosters timed every six months + 2 weeks. Boosters will therefore occur at the following time points after completion of the PVS: 6 months ± 2 weeks, 12 months ± 2 weeks, 18 months ± 2 weeks and 24 months ± 2 weeks.
Drug: Trastuzumab · Drug: GM-CSF
At the time of vaccine administration, a frozen solution of E75 acetate (1.5 mg/mL) is thawed and 1000mcg E75 peptide mixed thoroughly with 250mcg GM-CSF. This constitutes the NeuVax vaccine. Patients randomized to this arm will receive vaccinations of nelipepimut-S/GM-CSF administered intradermally every three weeks for six total vaccinations, 30-120 minutes after completion of trastuzumab infusion. The first vaccination will be given with the third dose of maintenance trastuzumab administered as monotherapy optimally, but may be given with later maintenance doses of trastuzumab, provided there are at least six remaining doses of trastuzumab to overlap with the primary vaccine series.
Also known as: nelipepimut-S
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 trastuzumab infusion will be given no sooner than three weeks and no later than 12 weeks after completion of chemotherapy/radiotherapy. Trastuzumab will be dosed at the recommended initial loading dose of 8 mg/kg and at recommended maintenance doses of 6 mg/kg q3wk.
Also known as: Herceptin
For patients randomized to the GM-CSF alone arm, they will receive inoculations of GM-CSF (250mcg) administered intradermally every three weeks for six total vaccinations, 30-120 minutes after completion of trastuzumab infusion. The first injection will be given with the third dose of maintenance trastuzumab administered as monotherapy optimally, but may be given with later maintenance doses of trastuzumab, provided there are at least six remaining doses of trastuzumab to overlap with the primary vaccine series.
Also known as: Leukine, Sargramostim
Invasive Disease-free Survival (DFS)
Compare invasive DFS between the two treatment groups from time of initiation of trastuzumab maintenance therapy (trasuzumab monotherapy) to time of invasive local, regional or distant recurrence, new primary, or death due to any cause. Disease state will be determined by the patients' own physicians at the individual study sites during their routine follow-up screening. This will occur for all enrolled patients, regardless of randomization, approximately 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 outcome measure of the trial is invasive DFS.
Time frame: Initiation of trastuzumab monotherapy through the end of the patient's fifth year of participation in the study.
Local and Systemic Toxicities
Standard local and systemic toxicities will be collected and graded per the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 graded toxicity scale. For both the inoculations during the primary vaccine/inoculation series and the 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. Additionally, patients will return to their study site 48-72 hours after inoculation for questioning regarding any systemic toxicity and local injection site reactions. When they return to their study site, the local reaction at the inoculation sites will be examined and measured.
Time frame: From the date of initiation of the vaccine or inoculation series and booster series up to 36 months.
Evaluate in Vivo and in Vitro Immune Responses
Immune responses will be primarily documented using the delayed type hypersensitivity (DTH) reaction and using the dextramer assay to enumerate peptide-specific CTL. Each of these measurements will be performed regardless of randomization. DTH reactions will be measured prior to initiation of the primary vaccine/inoculation series, one month ± 1 week after completion of the primary vaccine/inoculation series, and one month ± 1 week after the final booster inoculation. Dextramer measurements will be performed prior to initiating the primary vaccine/inoculation series as well as one month ± 1 week after completion of the vaccine/inoculation series. Additionally, these assays may be performed pre- and post-each booster. Alternatively, these assayed time points may also be performed all at once on frozen and banked cells.
Time frame: From the date of the first inoculation of Trastuzumab monotherapy to the end of the patient's fifth year of participation in the study.
| Milestone | Trastuzumab + NeuVax | Trastuzumab + GM-CSF |
|---|---|---|
| Started | 50 | 50 |
| Completed | 31 | 36 |
| Not completed | 19 | 14 |
Compare invasive DFS between the two treatment groups from time of initiation of trastuzumab maintenance therapy (trasuzumab monotherapy) to time of invasive local, regional or distant recurrence, new primary, or death due to any cause. Disease state will be determined by the patients' own physicians at the individual study sites during their routine follow-up screening. This will occur for all enrolled patients, regardless of randomization, approximately 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 outcome measure of the trial is invasive DFS.
| Participants | Trastuzumab + NeuVax | Trastuzumab + GM-CSF |
|---|---|---|
| Invasive Disease-free Survival (DFS) | 42 | 47 |
Standard local and systemic toxicities will be collected and graded per the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 graded toxicity scale. For both the inoculations during the primary vaccine/inoculation series and the 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. Additionally, patients will return to their study site 48-72 hours after inoculation for questioning regarding any systemic toxicity and local injection site reactions. When they return to their study site, the local reaction at the inoculation sites will be examined and measured.
| Participants | Trastuzumab + NeuVax | Trastuzumab + GM-CSF |
|---|---|---|
| Local and Systemic Toxicities | 46 | 43 |
Immune responses will be primarily documented using the delayed type hypersensitivity (DTH) reaction and using the dextramer assay to enumerate peptide-specific CTL. Each of these measurements will be performed regardless of randomization. DTH reactions will be measured prior to initiation of the primary vaccine/inoculation series, one month ± 1 week after completion of the primary vaccine/inoculation series, and one month ± 1 week after the final booster inoculation. Dextramer measurements will be performed prior to initiating the primary vaccine/inoculation series as well as one month ± 1 week after completion of the vaccine/inoculation series. Additionally, these assays may be performed pre- and post-each booster. Alternatively, these assayed time points may also be performed all at once on frozen and banked cells.
| Participants | Trastuzumab + NeuVax | Trastuzumab + GM-CSF |
|---|---|---|
| Evaluate in Vivo and in Vitro Immune Responses | 5 | 5 |
Collected over 36 months. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Trastuzumab + NeuVax | 0/50 (0%) | 3/50 (6%) | 43/50 (86%) |
| Trastuzumab + GM-CSF | 1/50 (2%) | 5/50 (10%) | 38/50 (76%) |
| Event | Trastuzumab + NeuVax | Trastuzumab + GM-CSF |
|---|---|---|
| Left Breast InfectionInfections and infestations | 1/50 | 1/50 |
| FeverGeneral disorders | 1/50 | 1/50 |
| Unintended PregnancyPregnancy, puerperium and perinatal conditions | 0/50 | 1/50 |
| Procedural Complication-Tram Flap FailureSurgical and medical procedures | 0/50 | 1/50 |
| SepsisGeneral disorders | 1/50 | 0/50 |
| UTI - PyelonephritisGastrointestinal disorders | 0/50 | 1/50 |
| Event | Trastuzumab + NeuVax | Trastuzumab + GM-CSF |
|---|---|---|
| Back PainMusculoskeletal and connective tissue disorders | 4/50 | 7/50 |
| WithdrawlsGeneral disorders | 7/50 | 7/50 |
| PruritusInfections and infestations | 6/50 | 4/50 |
| HeadacheNervous system disorders | 6/50 | 3/50 |
| Injection site reaction-ErythemaSkin and subcutaneous tissue disorders | 5/50 | 4/50 |
| FatigueGeneral disorders | 3/50 | 5/50 |
| Pain Injection SiteSkin and subcutaneous tissue disorders | 4/50 | 3/50 |
| MyalgiaMusculoskeletal and connective tissue disorders | 3/50 | 0/50 |
| FeverGeneral disorders | 1/50 | 2/50 |
| DiarrheaGastrointestinal disorders | 1/50 | 2/50 |
| Age, Categorical(Participants) | Trastuzumab + NeuVax | Trastuzumab + GM-CSF | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 42 | 44 | 86 |
| >=65 years | 8 | 6 | 14 |
| Sex: Female, Male(Participants) | Trastuzumab + NeuVax | Trastuzumab + GM-CSF | Total |
|---|---|---|---|
| Female | 50 | 50 | 100 |
| Male | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Trastuzumab + NeuVax | Trastuzumab + GM-CSF | Total |
|---|---|---|---|
| American Indian or Alaska Native | 1 | 0 | 1 |
| Asian | 4 | 2 | 6 |
| Native Hawaiian or Other Pacific Islander | 0 | 1 | 1 |
| Black or African American | 3 | 7 | 10 |
| White | 33 | 29 | 62 |
| More than one race | 2 | 2 | 4 |
| Unknown or Not Reported | 7 | 9 | 16 |
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