Description:
The purpose of this study is to determine the safety as well as the most effective dose of the alpha-lactalbumin vaccine (aLA breast cancer vaccine) to treat patients with non-metastatic triple negative breast cancer
The purpose of this study is to determine the safety as well as the most effective dose of the alpha-lactalbumin vaccine (aLA breast cancer vaccine) to treat patients with non-metastatic triple negative breast cancer
Not yet recruiting
Early Phase 1
Drug | Synonyms | Arms |
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α-lactalbumin vaccine | α-lactalbumin protein | α-lactalbumin and zymosan |
Zymosan | α-lactalbumin and zymosan |
This is an open-label, phase I dose-escalation trial in which successive cohorts of participants with high-risk triple-negative breast cancer will be treated with successively higher doses of α-lactalbumin and zymosan This aLA breast cancer vaccine is an investigational (experimental) drug that the study team believes will work by stimulating the immune system to fight the participant's cancer, in a way similar to the way the immune system fights off an infection after a vaccination for that infection. α-lactalbumin Vaccine is experimental because it is not approved by the Food and Drug Administration (FDA). A traditional "3+3" Phase I trial design will be employed to determined the Maximum Tolerated Dose (MTD). After identification of the MTD, if at least 1 participant has an immunologic response (correlative measurement), successively lower dose levels will be expanded to a total of 6 participants and immunologic response assessed. Enrollment will stop if a dose level is reached for which no responses are observed. Dose-Limiting toxicities (DLTs) in 2 or more of 6 participants, the next lower dose will be considered the new MTD. Objectives are to determine MTD, DLT incidence, and Lowest Immunologic Dose (LID). Toxicity will be assessed every 2 weeks until day 56 and at day 84 or at off-study. Participants will be offered participation in long-term follow-up involving contact or in-person follow-up for late toxicity and survival every 3 months for 2 years, every 6 months for an additional 3 years, and then annually for 10 years.
Name | Type | Description | Interventions |
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α-lactalbumin and zymosan | Experimental | Participants will be treated with successively higher doses of α-lactalbumin and zymosan in a traditional 3 + 3 phase I trial design. Treatment will involve a course of 3 vaccinations given every 2 weeks. Participants will be enrolled sequentially into 1 of 3 different dose levels each comprised of cohorts of 1-6 participants until the MTD has been identified (intra-patient dose escalation not permitted), after which the MTD will be expanded to 6 participants. Successively lower doses will be expanded to 6 participants until the lowest DL associated with immune response has been expanded. A dose level intermediate between 100 and 1000 mcg will be studied if the 1000 mcg dose is above the MTD and the 100 mcg dose does not produce the desired immunologic effect Dose Level (DL) 1: 10 microgram (mcg) a-lactalbumin + 10 mcg Zymosan DL2: 100 mcg a-lactalbumin + 100 mcg Zymosan DL3: 1000 mcg a-lactalbumin + 1000 mcg Zymosan |
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Inclusion Criteria: - Histologically proven invasive breast cancer. - Primary tumor must be ER-negative (ER in <1% of cells), PR-negative (PR in <1% of cells), and HER2-negative (0-1+ by immuno-histochemistry (IHC) or fluorescence in situ hybridization (FISH) ratio<2.0 with signal number <6/cell). - Participants must be high-risk, defined as either: - Pathologic stage IIA, IIB, IIIA, IIIB, or IIIC by American Joint Committee on Cancer (AJCC) 8, or - Residual invasive cancer in breast or regional nodes following preoperative chemotherapy. - Patients must have no convincing evidence of recurrent disease based on one of the following: - Bone scan and imaging scans of the chest/abdomen/pelvis or - 18F-2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) scan - (≥)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 - Treatment prior to enrollment must be consistent with contemporary National Comprehensive Cancer Network (NCCN) guidelines - Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 - Adequate major organ function, defined as: - white blood cell (WBC) count > 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 - Serum prolactin level must be < upper limits of normal (ULN); - Participants must have the ability to understand and the willingness to sign and provide a written informed consent document; - Participants 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. - Participants agrees not to use alternative therapies from the time of informed consent through 30 days following the last vaccine injection Exclusion Criteria: - Receipt of cytotoxic chemotherapy within 4 weeks of study entry - Radiation therapy within 4 weeks of study entry - Failure to recover from the toxicity of the previous therapy to CTCAE Grade 0-1, except for alopecia and grade 2 neuropathy - Need for systemic corticosteroid use (except as physiologic replacement, defined as prednisone 10 mg/day or equivalent). - Need for immunosuppression (e.g., for a history of organ transplantation) - Known HIV infection - Active or planned lactation or pregnancy - 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. - 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 - Participants receiving any other investigational agents within the last 4 weeks. - Participants with any known recurrence or metastasis - Participants with a history of another active invasive malignancy within 5 years of study entry - History of allergic reactions to α-lactalbumin, human milk (excluding lactose intolerance), Zymosan, or other agents used in this study - Participants 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 - Participants with known hyperprolactinemia - Participants being treated with drugs known to cause hyperprolactinemia - Known allergy to penicillin
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Measure: | MTD of α-lactalbumin vaccine |
Time Frame: | Day 84 |
Safety Issue: | |
Description: | MTD of an α-lactalbumin vaccine in participants with operable triple-negative breast cancer |
Measure: | Lowest Immunologic Dose (LID) of α-lactalbumin vaccine |
Time Frame: | Day 84 |
Safety Issue: | |
Description: | LID of α-lactalbumin vaccine in participants 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 |
Phase: | Early Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Not yet recruiting |
Lead Sponsor: | George T. Budd |
July 29, 2021