Phase II Trial of Combination Immunotherapy With NeuVax and Trastuzumab in High-risk HER2+ Breast Cancer Patients

NCT02297698 | Completed Phase 2 Results DMC

• 1 other identifier: 2014-0443
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 24

Brief Summary

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.

Conditions

Breast Cancer

Keywords

Breast cancer, NeuVax

Outcome Measures

Primary Outcomes (1)

• 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.

  Initiation of trastuzumab monotherapy through the end of the patient's fifth year of participation in the study.

Secondary Outcomes (2)

• Local and Systemic Toxicities

  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

  From the date of the first inoculation of Trastuzumab monotherapy to the end of the patient's fifth year of participation in the study.

Study Arms (2)

Trastuzumab + NeuVax

EXPERIMENTAL

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

Trastuzumab + GM-CSF

ACTIVE COMPARATOR

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

Interventions

NeuVax vaccine BIOLOGICAL

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

Trastuzumab + NeuVax

Trastuzumab DRUG

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

Trastuzumab + GM-CSF; Trastuzumab + NeuVax

GM-CSF DRUG

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

Trastuzumab + GM-CSF; Trastuzumab + NeuVax

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years or older
• Eastern Cooperative Oncology Group (ECOG) performance status 0,1
• AJCC stage I - III non-inflammatory, HER2-positive (according to ASCO-CAP guidelines 5) breast cancer
• Completed neoadjuvant therapy with an approved regimen that includes trastuzumab and at least four cycles (12 weeks) of taxane-containing chemotherapy and underwent surgery with final pathology showing evidence of residual disease in the breast or axilla (residual ductal carcinoma in situ or microinvasive disease not eligible) or underwent surgery as a first intervention and was found to be pathologically node-positive: ≥ 4 positive lymph nodes (pN2 or pN3) regardless of hormone receptor status or 1-3 positive lymph nodes (pN1) if hormone receptor negative. Patients with micrometastases (pN1mi) are not eligible.
• Completed an approved regimen of neoadjuvant or adjuvant therapy with an approved regimen that includes trastuzumab and at least four cycles (12 weeks) of taxane-containing chemotherapy with plan for completion of one year of trastuzumab therapy.
• Completed appropriate surgical therapy to include:
• Total mastectomy and axillary staging with sentinel lymph node dissection or axillary lymph node dissection (level I/II). Patients with a positive sentinel lymph node must have undergone a completion axillary lymph node dissection.
• Breast conserving surgery (BCS) and axillary staging with sentinel lymph node dissection or axillary lymph node dissection. Patients undergoing surgery as a first intervention 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. Patients receiving neoadjuvant chemotherapy that have a positive sentinel lymph node must have undergone a completion axillary lymph node dissection.
• Completed or receiving appropriate radiation therapy if indicated:
• 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 patients undergoing breast conserving surgery (BCS) as a first intervention, whole breast irradiation with or without a boost, and radiation to the infraclavicular and supraclavicular areas is required for patients with ≥ 4 positive lymph nodes. Radiation to the internal mammary lymph nodes is not required but is allowed at the discretion of the patient's treating radiation oncologist. For patients with 1-3 positive lymph nodes, whole breast irradiation with or without a boost is required. 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 medical oncologist.
• For patient's undergoing mastectomy after neoadjuvant chemotherapy post-mastectomy radiation to the chest wall, infraclavicular and supraclavicular areas is required for patients presenting with clinical N2 or N3 disease or with ≥ 4 positive lymph nodes identified pathologically at the time of surgery. 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, 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.
• HLA-A2+ or HLA-A3+ or HLA-A24+ or HLA-A26+
• LVEF \>50%, or an LVEF within the normal limits of the institution's specific testing (MUGA or ECHO)

You may not qualify if:

• AJCC Stage IV breast cancer
• NYHA stage 3 or 4 congestive heart failure
• Immune deficiency disease or known history of HIV, HBV, HCV
• Receiving immunosuppressive therapy including chronic steroids, methotrexate, or other known immunosuppressive agents
• 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 (\>3 inhalers including one containing steroids)
• Involved in other experimental protocols except with permission of other PI

Sponsors & Collaborators

• Cancer Insight, LLC: lead
• Genentech, Inc.: collaborator
• Sellas Life Sciences Group: collaborator

Study Sites (24)

Sarcoma Oncology Research Center, LLC

Santa Monica, California, 90403, United States

Location

St Joseph Heritage Healthcare

Santa Rosa, California, 95403, United States

Location

Sibley Memorial Hospital

Washington D.C., District of Columbia, 20016, United States

Location

University of Miami

Deerfield Beach, Florida, 33442, United States

Location

Memorial Breast Cancer Center

Hollywood, Florida, 33021, United States

Location

University of Miami

Kendall, Florida, 33176, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Florida Cancer Research Institute

Plantation, Florida, 33324, United States

Location

University of Miami

Plantation, Florida, 33324, United States

Location

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

Memorial Hospital of South Bend

South Bend, Indiana, 46601, United States

Location

Cancer Center of Kansas

Wichita, Kansas, 67212, United States

Location

Medstar Health (Union Memorial Hospital)

Baltimore, Maryland, 21218-2895, United States

Location

Medstar (Good Samaritan Hospital)

Baltimore, Maryland, 21239, United States

Location

The Valley Hospital

Paramus, New Jersey, 07652, United States

Location

University of New Mexico Cancer Center

Albuquerque, New Mexico, 87106, United States

Location

New Mexico Cancer Care Alliance/Presbyterian Cancer Center

Albuquerque, New Mexico, 87110, United States

Location

Tisch Cancer Institute/Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

North Shore Hematology Oncology Associates

The Bronx, New York, 10469, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Texas Oncology (Cancer Care Centers of South Texas)

San Antonio, Texas, 78217, United States

Location

University of Virginia Human Immune Therapy Center

Charlottesville, Virginia, 22908, United States

Location

Providence Regional Medical Center

Everett, Washington, 98201, United States

Location

Ascension/ Columbia St. Mary's

Milwaukee, Wisconsin, 53211, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

HER2 peptide (369-377); Trastuzumab; Granulocyte-Macrophage Colony-Stimulating Factor; sargramostim

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors

Results Point of Contact

• Title: Dr. George Peoples
• Organization: LumaBridge

gpeoples@lumabridge.com

210 557 4291

Study Officials

• COL (ret) George E Peoples, MD, FACS

  LumaBridge

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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

Study Record Dates

• First Submitted: November 14, 2014
• First Posted: November 21, 2014
• Study Start: October 1, 2014
• Primary Completion: December 1, 2021
• Study Completion: December 1, 2021
• Last Updated: December 12, 2023
• Results First Posted: December 12, 2023

Record last verified: 2023-11

Locations

US (24)