Phase II Study of Allo LMI Vaccine With IL-2 for Stable Metastatic Breast Ca

This study has suspended participant recruitment.
(interim analysis)
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT00784524
First received: November 1, 2008
Last updated: May 28, 2013
Last verified: May 2013
  Purpose

RATIONALE: Vaccines may help the body build an effective immune response to kill tumor cells. Aldesleukin may stimulate the white blood cells to kill breast cancer cells. Giving vaccine therapy together with aldesleukin may be a more effective treatment for metastatic breast cancer.

PURPOSE: This phase II trial is studying how well giving vaccine therapy together with aldesleukin works in treating women with metastatic breast cancer.


Condition Intervention Phase
Breast Cancer
Biological: allogeneic large multivalent immunogen breast cancer vaccine
Biological: aldesleukin
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Allogeneic Large Multivalent Immunogen (LMI) Vaccine and IL-2 for the Treatment of Stable Metastatic Breast Cancer

Resource links provided by NLM:


Further study details as provided by Masonic Cancer Center, University of Minnesota:

Primary Outcome Measures:
  • Disease Response [ Time Frame: Beginning at 2 months ] [ Designated as safety issue: No ]
    Percentage of patients achieving complete response, partial response, or disease stabilization as assessed by RECIST criteria


Secondary Outcome Measures:
  • Immune response [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
    Immune responses will be assessed by DTH responses to LMI, IFN-gamma production by CD8+ T cells using the ELISPOT assay, and CD8+ T cell binding to HLA-A2 multimers complexed with breast cancer-derived peptides (multimer analysis).

  • Progression-free survival [ Time Frame: Baseline Compared to 1 Cycle and Baseline to After Chemotherapy ] [ Designated as safety issue: No ]
    Progression free survival will be measured in months from time of response to time of disease progression as defined by RECIST (appendix II), "at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s)."

  • Overall survival [ Time Frame: 1 Year and 2 Years ] [ Designated as safety issue: No ]
    Overall survival at one and two years will be determined by longitudinal follow-up


Estimated Enrollment: 39
Study Start Date: September 2008
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LMI Vaccination + IL-2
Patients receiving allogeneic large multivalent immunogen breast cancer vaccine and aldesleukin.
Biological: allogeneic large multivalent immunogen breast cancer vaccine
Allogeneic large multivalent immunogen breast cancer vaccine (1 x 10^7, 5-μm silica spheres) will be given as an intradermal injection every 28 days (+/- 3 days). Each vaccine dose will be 0.2 ml.
Other Name: LMI
Biological: aldesleukin
Subcutaneous aldesleukin (10 x 10^6 International Units) will be given on day 7 and day 8 after each LMI injection.
Other Names:
  • Interleukin-2
  • IL-2
  • Proleukin

Detailed Description:

OBJECTIVES:

Primary

  • To determine the efficacy of allogeneic large multivalent immunogen (LMI) vaccine and aldesleukin, as defined by clinical benefit rate (percentage of patients demonstrating a complete response, partial response, or disease stabilization as assessed by RECIST criteria), in women with stable metastatic breast cancer.

Secondary

  • To measure the immune response in patients treated with this regimen.
  • To determine the progression-free survival of patients treated with this regimen.
  • To determine the 1- and 2-year overall survival rates in patients treated with this regimen.
  • To determine the safety profile and toxicity of this regimen in these patients.

OUTLINE: Patients receive allogeneic large multivalent immunogen (LMI) vaccine intradermally on day 1 and aldesleukin subcutaneously on days 7 and 8. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression after 2 courses of vaccine therapy resume the chemotherapy regimen for which prior disease stabilization was achieved. Beginning 2-4 days after completion of chemotherapy, patients receive one dose of LMI vaccine followed by aldesleukin on days 7 and 8. Patients achieving at least stable disease continue to receive LMI vaccine and aldesleukin as above. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Peripheral blood mononuclear cell samples are collected periodically for research studies. Samples are analyzed to assess the frequency of leukocyte subsets (including B cells, T cells, NK cells, and monocytes) via flow cytometry; frequency of T-regs (T cells that express CD4, CD25, and FoxP3); and responses to keyhole limpet hemocyanin and tetanus toxoid via ELISA assay. Other immunological studies are also performed.

After completion of study therapy, patients are followed every 3 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Stage IV, metastatic breast cancer, confirmed by histology or cytology.

    • Disease must be refractory to hormone therapy for tumors that estrogen and/or progesterone receptor positive
    • Disease must be refractory to trastuzumab for tumors that are HER2 positive
    • Disease must be responsive to chemotherapy such that regression or at least stabilization occurs

      • Stable disease is defined as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease
      • Measurement of regressed or stable disease must be confirmed by repeat evaluation no less than 4 weeks after the initial determination.
  • Prior systemic chemotherapy, immunotherapy, biological therapy, or investigational drug therapy is allowed if at least 4 weeks since last treatment.

    • Patient must recover from the acute toxic effects of the treatment prior to study enrollment.
    • There is no limit as to the number of previous chemotherapy regimens received.
  • Disease status may be measurable or non-measurable
  • Karnofsky performance status >70%
  • Women, age 18 years or older
  • Adequate organ function within 14 days of study registration including the following:

    • Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count (ANC) ≥ 1.5 x 10^9/L, platelets ≥75 x 10^9/L, and hemoglobin ≥ 8.0 g/dL
    • Hepatic: bilirubin ≤ 3 times the upper limit of normal (× ULN) for patients without tumor involvement of the liver and ≤ 5 X ULN for patients with tumor involvement of the liver; aspartate transaminase (AST) ≤ 2.5 × ULN for patients without tumor involvement of the liver and ≤ 5 X ULN for patients with tumor involvement of the liver
    • Renal: creatinine ≤ 2.0 mg/dL
  • Must share at least one class I HLA allele with the HLA-type SKBR3 cell (class I alleles A2, A3, B14, B40, C3, C8)
  • Meets eligibility criteria for and agrees to enroll in "MT1999-06: Vaccination with Tetanus Toxoid and Keyhole Limpet Hemocyanin (KLH) to Assess Antigen-Specific Immune Responses" (IRB # 9904M01581, CPRC #2002LS032). Patients who have had tetanus toxoid within the last 7 years will not receive the tetanus vaccine component. For patients who do not know the year of their last tetanus vaccine, tetanus toxoid will be given per protocol. Subjects allergic to seafood will not be co-enrolled into MT1996-06.
  • Women of childbearing potential and their partners are required to use an effective method of contraception (ie, a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) during the study and for 3 months after the last dose of study drug.
  • Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.

Exclusion criteria:

  • History of untreated or active brain metastases or positive brain scan at enrollment. Patients with previously treated brain metastases are eligible if stable by CT or MRI for at least 3 months.
  • Concurrent malignancy other than non-melanoma skin cancer or carcinoma in situ of the cervix
  • Active infection
  • Solid organ transplantation or autoimmune diseases requiring systemic immunosuppressive therapy; however, topical or inhalational steroids are allowed.
  • Symptomatic pulmonary disease (symptoms of dyspnea or rales, wheezes or rhonchi on physical exam) will require pulmonary function testing (PFTs). Those with FEV1 <50% of predicted or corrected DLCO <50% are not eligible.
  • Patients with cardiac disease such as recent myocardial infarction (< 3 months prior), unstable angina, or heart failure requiring medical intervention will undergo cardiac evaluation. Cardiac testing may include ECG, MUGA or echocardiogram, and/or thallium stress test as indicated to evaluate cardiac risks. Those patients with exercise-induced ischemia or an ejection fraction by MUGA or echocardiogram < 40% are not eligible.
  • Hypersensitivity to any component of the vaccine, including Thimerosal, a mercury derivative, is a contraindication (taken from tetanus toxoid package insert).
  • The occurrence of any type of neurologic symptoms to tetanus vaccine in the past is a contraindication to further use (taken from tetanus toxoid package insert).
  • Pregnant (positive pregnancy test) or lactating women. Use of LMI vaccine during pregnancy is not approved for use by the FDA during pregnancy. IL-2 is pregnancy category C - risk in pregnancy cannot be ruled out.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00784524

Locations
United States, Minnesota
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
Principal Investigator: Douglas Yee, MD Masonic Cancer Center, University of Minnesota
  More Information

Additional Information:
No publications provided

Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT00784524     History of Changes
Other Study ID Numbers: 2007LS094, 0802M25946
Study First Received: November 1, 2008
Last Updated: May 28, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Masonic Cancer Center, University of Minnesota:
stage IV breast cancer
recurrent breast cancer
metastatic breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Aldesleukin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on September 16, 2014