Clinical Trials /

Adjuvant Therapy With an Alpha-lactalbumin Vaccine in 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

Related Conditions:
  • Invasive Breast Carcinoma
Recruiting Status:

Not yet recruiting


Early Phase 1

Trial Eligibility



  • Brief Title: Adjuvant Therapy With an Alpha-lactalbumin Vaccine in Triple-Negative Breast Cancer
  • Official Title: Phase I Trial of Adjuvant Therapy With an Alpha-lactalbumin Vaccine in Patients With Non-Metastatic Triple-Negative Breast Cancer at High Risk of Recurrence

Clinical Trial IDs

  • SECONDARY ID: W81XWH-17-1-0593
  • SECONDARY ID: W81XWH-17-1-0592
  • NCT ID: NCT04674306


  • Pathologic Stage IIA-IIIC Triple-Negative Breast Cancer
  • TNBC - Triple-Negative Breast Cancer
  • Residual Disease


α-lactalbumin vaccineα-lactalbumin proteinα-lactalbumin and zymosan
Zymosanα-lactalbumin and zymosan


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

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.

Trial Arms

α-lactalbumin and zymosanExperimentalParticipants 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
  • α-lactalbumin vaccine
  • Zymosan

Eligibility 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 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

          -  Patients must have no convincing evidence of recurrent disease based on one of the

               -  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

Primary Outcome Measures

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

Secondary Outcome Measures

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

Last Updated

July 29, 2021