Combination Immunotherapy With Herceptin and the HER2 Vaccine E75 in Low and Intermediate HER2-expressing Breast Cancer Patients to Prevent Recurrence

Status: Completed

Location: See all (29) locations...

Intervention Type: Drug

Study Type: Interventional

Study Phase: Phase 2

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.

Eligibility

Participation Requirements

Sex: Female

Minimum Age: 18

Healthy Volunteers: f

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⁃ 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.

Locations

United States

California

Samuel Oschin Comprehensive Cancer Institute - Cedars Sinai Medical Center

Beverly Hills

Sarcoma Oncology Research Center, LLC

Santa Monica

St. Joseph Heritage Healthcare

Santa Rosa

Washington, D.c.

Katzen Cancer Research Center, George Washington University

Washington

Sibley Memorial Hospital

Washington

Florida

University of Miami

Deerfield Beach

University of Miami

Kendall

University of Miami

Miami

Florida Cancer Research Institute

Plantation

University of Miami

Plantation

H. Lee Moffitt Cancer Center & Research Institute, Inc

Tampa

Hawaii

University of Hawaii Cancer Center

Honolulu

Indiana

Franciscan Health Indianapolis

Indianapolis

Memorial Hospital of South Bend

South Bend

Kansas

Cancer Center of Kansas

Wichita

Maryland

MedStar Health - Good Samaritan Hospital

Baltimore

Medstar Health - Union Memorial Hospital

Baltimore

Medstar Health - Weinberg Cancer Institute at Franklin Square

Baltimore

New Jersey

The Valley Hospital

Paramus

New York

North Shore Hematology Oncology Associates

Bronx

Tisch Cancer Institute/Icahn School of Medicine at Mount Sinai

New York

Oregon

Legacy Health, Legacy Good Samaritan Medical Center

Portland

Pennsylvania

Thomas Jefferson University - Kimmel Cancer Center

Philadelphia

Texas

University of Texas M.D. Anderson Cancer Center

Houston

Texas Oncology (Cancer Care Centers of South Texas)

San Antonio

Virginia

Virginia Cancer Specialists

Fairfax

Washington

Providence Regional Medical Center

Everett

Swedish Cancer Institute

Seattle

Wisconsin

Columbia St. Mary's

Milwaukee

Time Frame

Start Date: 2013-05-21

Completion Date: 2018-09-28

Participants

Target number of participants: 275

Treatments

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.

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.

Related Therapeutic Areas

Breast Cancer

Combination Immunotherapy With Herceptin and the HER2 Vaccine E75 in Low and Intermediate HER2-expressing Breast Cancer Patients to Prevent Recurrence

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