Overview

Vaccine Therapy and 1-MT in Treating Patients With Metastatic Breast Cancer

Status:
Completed
Trial end date:
2018-02-27
Target enrollment:
0
Participant gender:
All
Summary
This randomized phase I/II trial studies the side effects and best dose of vaccine therapy and to see how well it works when given together with 1-methyl-D-tryptophan (1-MT) in treating patients with metastatic breast cancer. Vaccines made from a person's tumor cells and white blood cells may help the body build an effective immune response to kill tumor cells.
Phase:
Phase 1/Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
H. Lee Moffitt Cancer Center and Research Institute
Collaborator:
National Cancer Institute (NCI)
Treatments:
Tryptophan
Vaccines
Criteria
Inclusion Criteria:

- In the phase I patients with any solid tumor positive for p53 by IHC (>= 5% of cells
with any degree of nuclear staining) staining; for the phase II, patients must have
histologically or cytologically confirmed metastatic invasive breast cancer that is
positive for p53 staining by IHC (>= 5% of cells with any degree of nuclear staining);
patients will sign a separate consent for the p53 testing, and those that meet the
above requirements will then be allowed to sign the vaccine trial consent

- Patients must have measurable disease, defined as at least one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded) as >=
20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT)
scan

- There are no restrictions on prior therapies for the phase I part of the trial; for
the phase II, patients may have received up to 2 prior lines of chemotherapy (not
counting endocrine therapy lines) with the last dose of chemotherapy given 3 weeks (6
weeks for nitrosoureas and mitomycin C) prior to initiation on this study

- Life expectancy of greater than 4 months

- Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)

- Leukocytes >= 3,000/μL

- Absolute neutrophil count >= 1,500/μL

- Platelets >= 100,000/μL

- Total bilirubin within normal institutional limits unless patient has Gilbert's
disease

- Aspartate aminotransferase (AST) /serum glutamic oxaloacetic transaminase (SGOT)
/alanine aminotransferase (ALT) /serum glutamic pyruvate transaminase (SGPT) =< 2.5 X
institutional upper limit of normal

- Creatinine within normal institutional limits OR creatinine clearance >= 60
mL/min/1.73 m^2 for patients with creatinine levels above institutional normal

- Thyroid-stimulating hormone (TSH), luteinizing hormone (LH), follicle-stimulating
hormone (FSH), adrenocorticotropic hormone (ACTH) showing normal pituitary function;
these values may deviate if in the opinion of the investigator these are normal
pituitary responses to another endocrine condition such as suboptimally treated
hypothyroidism

- Patients with known brain metastases will only be eligible after their tumors have
been treated with definitive resection and/or radiotherapy and they are neurologically
stable for at least 1 month off steroids

- No history of gastrointestinal disease causing malabsorption or obstruction such as
but not limited to Crohn's disease, celiac sprue, tropical sprue, bacterial
overgrowth/blind loop syndrome, gastric bypass surgery, strictures, adhesions,
achalasia, bowel obstruction, or extensive small bowel resection

- Sexually active women of child-bearing potential must agree to use two forms of
contraception (hormonal and barrier method of birth control or abstinence) prior to
study entry and for the duration of study participation; males should use barrier
contraception or abstinence during the study; use of contraception or abstinence
should continue for a minimum of 1 month after completion of the study; should a woman
become pregnant or suspect she is pregnant while participating in this study, she
should discontinue the study drug and inform her treating physician immediately; a
pregnancy test is required prior to study enrollment and monthly while on treatment
with 1-MT for all women of child-bearing potential; also men should be discouraged
from fathering children while on treatment

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- Patients who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study or those who have not
recovered from adverse events due to agents administered more than 3 weeks earlier

- Patients may not receive any other investigational agents or chemotherapy to treat
their underlying malignancy while on study; patients who are stable on prior endocrine
therapies (i.e. aromatase inhibitors, tamoxifen, and fulvestrant) may stay on these
treatments

- Patients with known untreated brain metastases are excluded from this clinical trial;
patients with stable previously treated lesions in a patient off steroids and
radiation for 1 month are not excluded

- History of allergic reactions (significant urticaria, angioedema, anaphylaxis)
attributed to compounds of similar chemical or biologic composition to
1-methyl-D-tryptophan; this would include L-tryptophan or 5-hydroxy-tryptophan
supplements

- No supplements containing L-tryptophan or derivatives thereof are allowed to be taken
while on study; also ingestion of antacid compounds should be timed a minimum of 2
hours before or after ingestion of 1-MT

- Patients with any active autoimmune disease (i.e. psoriasis, extensive atopic
dermatitis, asthma, inflammatory bowel disease ([IBD), multiple sclerosis (M.S.),
uveitis, vasculitis), chronic inflammatory condition, or any condition requiring
concurrent use of any systemic immunosuppressants or steroids for any reason would be
excluded from the study; any patient with an allo-transplant of any kind would be
excluded as well; this would include those with a xenograft heart valve to avoid the
potential risk of any immune reaction causing valvular degeneration; mild-intermittent
asthma requiring only occasional beta-agonist inhaler use or mild localized eczema
will not be excluded

- Uncontrolled concurrent illness including, but not limited to ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, myocardial
infarction or percutaneous coronary interventions within the last 6 months, cardiac
arrhythmia, active autoimmune diseases, or major psychiatric illness/social situations
that would limit compliance with study requirements as judged by the primary
investigator at each site; those with well controlled, chronic medical conditions
under the supervision of the patient's primary physician (i.e. hypertension,
hyperlipidemia, coronary heart disease, diabetes mellitus) would not be excluded

- Pregnant women are excluded from this study; breastfeeding should be discontinued if
the mother is treated with 1-methyl-D-tryptophan

- Human immunodeficiency virus (HIV)-positive patients and those with other
acquired/inherited immunodeficiencies are ineligible

- Patients with more than one active malignancy at the time of enrollment

- Patients who have received any prior experimental active immunotherapy consisting of
targeted monoclonal antibodies or pharmaceutical compounds are excluded; prior
experimental vaccine patients may be enrolled if approved by the principal
investigator (PI); patients who have received commercially available active
immunotherapies such as adjuvant interferon must have completed therapy over 1 year
prior to enrollment and have no evidence of autoimmune sequelae; prior therapy with
approved monoclonal antibodies such as bevacizumab, cetuximab, panitumumab, or
trastuzumab is allowed; concurrent treatment with these agents and the study treatment
is not allowed

- Human epidermal growth factor receptor 2 positive (HER2+) patients (IHC 3+ and/or
fluorescent in situ hybridization [FISH] HER2/centromere portion of chromosome 17
[CEP17] ratio > 2) who require treatment with trastuzumab or lapatinib are not
eligible for this study