Adjuvant Therapy With an Alpha-lactalbumin Vaccine in Triple-Negative Breast Cancer
Study Details
Study Description
Brief Summary
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Early Phase 1 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: α-lactalbumin and zymosan 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 5 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. Dose Level (DL) 1: 10 microgram (mcg) a-lactalbumin + 10 mcg Zymosan DL2: 100 mcg a-lactalbumin + 10 mcg Zymosan DL3: 500 mcg a-lactalbumin + 10 mcg Zymosan DL4: 500 mcg a-lactalbumin + 30 mcg Zymosan DL5: 500 mcg a-lactalbumin + 60 mcg Zymosan |
Biological: α-lactalbumin vaccine
α-lactalbumin vaccine will be administered subcutaneously in rotating sites (vaccine will not be administered in the arms of any participant, due to likelihood of prior bilateral mastectomy).
DL1: 10 mcg
DL2: 100 mcg
DL3-5: 500 mcg
Other Names:
Biological: Zymosan
Adjuvant used in vaccine preparation
DL1-3: 10 mcg
DL4: 30 mcg
DL5: 60 mcg
|
Outcome Measures
Primary Outcome Measures
- MTD of α-lactalbumin vaccine [Day 84]
MTD of an α-lactalbumin vaccine in participants with operable triple-negative breast cancer
Secondary Outcome Measures
- Lowest Immunologic Dose (LID) of α-lactalbumin vaccine [Day 84]
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
Eligibility Criteria
Criteria
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 IHC or FISH ratio<2.0 with signal number <6/cell), or consistent with contemporary NCCN guidelines (https://www.nccn.org/).
-
Patients must be high risk, defined as either:
-
Pathologic stage IIA, IIB, IIIA, IIIB, or IIIC by 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
-
FDG 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 triplenegative breast cancer [33, 34].
-
Treatment prior to enrollment must be consistent with contemporary NCCN guidelines, found at: https://www.nccn.org/.
-
Age >18 years.
-
ECOG Performance Status 0-1.
-
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.
-
Serum prolactin level must be < upper limits of normal (ULN).
-
Subjects must have the ability to understand and the willingness to sign and provide a written informed consent document.
-
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.
-
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:
-
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.
-
Subjects receiving any other investigational agents within the last 4 weeks.
-
Subjects with any known recurrence or metastasis.
-
Subjects 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.
-
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.
-
Subjects with known hyperprolactinemia.
-
Subjects being treated with drugs known to cause hyperprolactinemia (see appendix 2).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Cleveland Clinic, Case Comprehensive Cancer Center | Cleveland | Ohio | United States | 44915 |
Sponsors and Collaborators
- George T. Budd
- United States Department of Defense
Investigators
- Principal Investigator: George T Budd, MD, Cleveland Clinic, Case Comprehensive Cancer Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CASE6119
- W81XWH-17-1-0593
- W81XWH-17-1-0592