Details
Title Phase I Trial of Adjuvant Therapy With an a-lactalbumin Vaccine in Patients With Non-Metastatic Triple-Negative Breast Cancer at High Risk of Recurrence
IRB CASE6119
CC 21-135
Hospital Main Campus
Stage High Risk, Stage 2, Stage 3
Phase Phase 1
Disease Breast, Breast - Triple Negative Breast Cancer (TNBC)
Drug Alpha-lactalbumin Vaccine
Description
2.1 Primary Objective: To define the toxicity of an α-lactalbumin vaccine and determine the maximum tolerated dose (MTD) in patients with non-metastatic high-risk triple-negative breast cancer.
2.2 Secondary Objective: To define the Lowest Immunologic Dose (LID) of α-lactalbumin vaccine in patients with operable triple-negative breast cancer, based on ELISPOT assays to assess the ability to induce a pro-inflammatory T cell response consistent with tumor protection. This assessment will be determined using the ELISPOT assay to determine peripheral blood frequencies of T cells that produce interferon-gamma (IFNγ; type-1) and IL-17 (type-17) in response to recombinant human α-lactalbumin.
2.3 Exploratory Objective: To determine the Optimal Immunologic Dose (OID) of α-lactalbumin vaccine in patients with non-metastatic triple-negative breast cancer, based on ELISPOT assays of IFNγ and IL-17 production in response to α-lactalbumin stimulation.
2.4 Correlative Objectives: To examine the cellular response to α-lactalbumin vaccine in a population of patients with operable triple-negative breast cancer using ELISPOT assays of IFNγ and IL-17 production in response to α-lactalbumin stimulation.
To examine the humoral response to α-lactalbumin vaccine in a population of patients with operable triple-negative breast cancer, using an ELISA assay.
Inclusion Criteria
Triple Negative Cohort
4.1.1.1 Histologically proven invasive breast cancer.
4.1.1.2 Primary tumor must be ER-negative (ER in <1% of cells), PR-negative (PR in <1% of cells), and HER2-negative (0-1+ by IHC or FISH ratio<2.0 with signal number <6/cell), or consistent with contemporary NCCN guidelines (https://www.nccn.org/).
4.1.1.3 Patients must be high risk, defined as either:
4.1.1.3.1 Pathologic stage IIA, IIB, IIIA, IIIB, or IIIC by AJCC 8, or
4.1.1.3.2 Residual invasive cancer in breast or regional nodes following pre-operative chemotherapy.
4.1.1.4. Patients must have no convincing evidence of recurrent disease based on one of the following:
4.1.4.1 Bone scan and imaging scans of the chest/abdomen/pelvis or
4.1.4.2 FDG PET scan.
4.1.1.5 >1 months since last active therapy (chemotherapy, radiation therapy, or surgery) and <36 months since the initiation of treatment for the current cancer, based on the period of highest risk for patients with Stages I-III triple-negative breast cancer [33, 34].
4.1.1.6 Treatment prior to enrollment must be consistent with NCCN guidelines extant at the time treatment was given, found at: https://www.nccn.org/.
4.1.1.7 Age >18 years.
4.1.1.8 ECOG Performance Status 0-1.
4.1.1.9 Adequate major organ function, defined as:
WBC > 3,000/mcl,
hemoglobin > 10.0 gm/dL,
platelets > 100,000/mcL,
total bilirubin within normal limits,
ALT/AST <3 x upper limits of normal (ULN),
serum creatinine < 1.5 x ULN.
4.1.1.10 Serum prolactin level must be < upper limits of normal (ULN).
4.1.1.11 Subjects must have the ability to understand and the willingness to sign and provide a written informed consent document.
4.1.1.12 Subjects must have archival tissue available for potential correlative studies (e.g., assays for α-lactalbumin expression or tumor infiltrating lymphocytes), but tumors will not be required to exhibit overexpression of α-lactalbumin for enrollment.
4.1.1.13 Subject agrees not to use alternative therapies from the time of informed consent through 30 days following the last vaccine injection (see section 6.6.1.3).
Prevention cohort
4.2.1.1 Participant must have a high risk for developing triple-negative breast cancer, defined as: carrying a deleterious mutation in BRCA1, PALB2
4.2.1.4. Patients must have no evidence of breast cancer based on both of the following:
4.2.1.4.1 Negative mammography or breast MRI within 180 days
4.2.1.4.2 Negative breast examination by a physician or advanced practice practitioner within 30 days
4.2.1.5 Age >18 years.
4.2.1.6 ECOG Performance Status 0-1.
4.2.1.7 Adequate major organ function, defined as:
WBC > 3,000/mcl,
hemoglobin > 10.0 gm/dL,
platelets > 100,000/mcL,
total bilirubin within normal limits,
ALT/AST <3 x upper limits of normal (ULN),
serum creatinine < 1.5 x ULN.
4.2.1.8 Serum prolactin level must be < upper limits of normal (ULN).
4.2.1.9 Subjects must have the ability to understand and the willingness to sign and provide a written informed consent document.
4.2.1.10 Subject agrees not to use alternative therapies from the time of informed consent through 30 days following the last vaccine injection (see section 6.6.1.3).
Exclusion Criteria
Triple Negative Cohort
4.1.2.1 Receipt of cytotoxic chemotherapy within 4 weeks of study entry.
4.1.2.2 Radiation therapy within 4 weeks of study entry.
4.1.2.3 Failure to recover from the toxicity of the previous therapy to CTCAE Grade 0-1, except for alopecia and grade 2 neuropathy.
4.1.2.4 Need for systemic corticosteroid use (except as physiologic replacement, defined as prednisone 10 mg/day or equivalent).
4.1.2.5 Need for immunosuppression (e.g., for a history of organ transplantation).
4.1.2.6 Known HIV infection.
4.1.2.7 Active or planned lactation or pregnancy.
4.1.2.8 Patients taking or planning to take oral contraceptives will be excluded, as there is some evidence that such agents can induce lactational foci. This includes patients using hormone containing IUD’s.
4.1.2.9 Refusal to use effective non-hormonal contraception. Acceptable contraception methods include but may not be limited to barrier contraception (diaphragm or condom), non-hormonal intrauterine device, vasectomy of male partner.
4.1.2.10 Subjects receiving any other investigational agents within the last 4 weeks.
4.1.2.11 Subjects with any known recurrence or metastasis.
4.1.2.12 Subjects with a history of another active invasive malignancy within 5 years of study entry.
4.1.2.13 History of allergic reactions to α-lactalbumin, human milk (excluding lactose intolerance), zymosan, or other agents used in this study.
4.1.2.14 Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
4.1.2.15 Subjects with known hyperprolactinemia.
4.1.2.16 Subjects being treated with drugs known to cause hyperprolactinemia (see appendix 2).
Prevention cohort
4.2.2.1 Receipt of cytotoxic chemotherapy within 4 weeks of study entry (including for benign indications).
4.2.2.2 Radiation therapy within 4 weeks of study entry (including for benign indications).
4.2.2.3 Need for systemic corticosteroid use (except as physiologic replacement, defined as prednisone 10 mg/day or equivalent).
4.2.2.4 Need for immunosuppression (e.g., for a history of organ transplantation).
4.2.2.5 Known HIV infection.
4.2.2.6 Active or planned lactation or pregnancy.
4.2.2.7 Patients taking or planning to take oral contraceptives will be excluded, as there is some evidence that such agents can induce lactational foci. This includes patients using hormone containing IUD’s.
4.2.2.8 Refusal to use effective non-hormonal contraception. Acceptable contraception methods include but may not be limited to barrier contraception (diaphragm or condom), non-hormonal intrauterine device, vasectomy of male partner.
4.2.2.9 Subjects receiving any other investigational agents within the last 4 weeks.
4.2.2.10 Subjects with a history of invasive malignancy within 5 years of study entry.
4.2.2.11 History of allergic reactions to α-lactalbumin, human milk (excluding lactose intolerance), zymosan, or other agents used in this study.
4.2.2.12 Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
4.2.2.13 Subjects with known hyperprolactinemia.
4.2.2.14 Subjects being treated with drugs known to cause hyperprolactinemia (see appendix 2).
