Clinical trial NCT02019524: Phase Ib Trial of Two Folate Binding Protein Peptide Vaccines (E39 and J65) in Breast and Ovarian Cancer Patients
Official title: Phase Ib Trial of Two Folate Binding Protein (FBP) Peptide Vaccines (E39 and J65) in Breast and Ovarian Cancer Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Breast Cancer
Ovarian Cancer
Keywords: Stage I breast cancer
Stage II breast cancer
Stage IIIA, IIIB, and IIIC breast cancer
Male breast cancer
Ovarian cancer
Lead sponsor: San Antonio Military Medical Center
Sponsor class: FED
Collaborators: name: M.D. Anderson Cancer Center
First posted: 2013-12-24
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This is a single-center, randomized, single-blinded, three-arm phase Ib study of the folate binding protein vaccines E39 and J65. The study target population are patients with breast or ovarian cancer diagnosis who have been treated and are without evidence of disease. Disease-free subjects after standard of care multi-modality therapy will be screened and HLA typed. E39 and J65 are cytotoxic T-lymphocyte-eliciting peptide vaccines that are restricted to HLA-A2+ patients (approximately 50% of the U.S. population).

Detailed description: The study is a prospective, randomized, non-blinded, single-center Phase Ib trial. Patients will be identified that have a diagnosis of breast or ovarian cancer, have completed their standard courses of therapy and are disease-free. They will be properly screened, counseled and consented prior to enrollment. Once enrolled, each patient's blood will be tested for HLA-A2 status (approximately 50% will be HLA-A2+). Additionally, their tumors will be tested for FBP-expression and this information will be tracked for purposes of correlative science.

Patients who are HLA-A2+ will be stratified based on cancer diagnosis (breast versus ovarian), then randomized by computer tables to one of three arms for the PVS. Each arm will receive 6 monthly injections of peptide + GM-CSF. Arm A will receive six inoculations with E39 peptide; arm B will receive three inoculations with E39 followed by three with J65; and arm C will receive three inoculations with J65, followed by three of E39. Since J65 has not been previously used in humans, a two week waiting period will be instituted between the first and second patients enrolled in either Arm B or C. Immunologic data will be assessed at 1 month and 6 months (±2 wks) after the PVS, specifically ex vivo immunologic recognition of E39 and J65 will be assessed by clonal expansion using a dextramer assay and the in vivo response will be assessed by Delayed Type Hypersensitivity (DTH). Immunologic recognition of E39 will be the primary endpoint, with recognition of J65 serving as an additional data point. The 6 month post-PVS immunologic data will then be used to assess each patient for significant residual immunity (SRI), defined as ≥2-fold increase in E39-specific CD8+ T-cells from the pre-vaccination level. Patients will then be sorted into two groups: those with SRI and those without. Patients within each group will then be randomized to receive one booster of either J65 or E39. Each patient will return to clinic within 1-2 weeks of their 6mo post-PVS visit to receive their single booster inoculation. This second randomization will result in four groups: 1) patients with SRI receiving E39; 2) patients with SRI receiving J65; 3) patients without SRI receiving E39; 4) patients without SRI receiving J65. Immunologic data will then again be gathered at 1 month (±2 wks) and 6 months (±2 wks) post-booster. This final immunologic data will be analyzed for differences between the four groups. Additionally, toxicity data will be gathered.

Patients will be monitored closely for one hour after each inoculation with questioning, serial exams, and vital signs every 15 minutes. Patients will then be asked to return to the vaccine clinic 48-72 hours after each inoculation for questioning regarding any local or systemic toxicity and to examine and measure the local reaction at the vaccination sites. The graded toxicity scale (NCI Common Terminology Criteria for Adverse Events, v4.03) will be utilized to assess local and systemic toxicity. GM-CSF dose reduction may be required if \>10cm of erythema and induration is seen at the injection site after any given inoculation.

Eligibility criteria: Inclusion Criteria:

1. Patients must have breast or ovarian cancer
2. Patients must have completed primary breast or ovarian cancer therapy (i.e., surgery, chemotherapy, immunotherapy and/or radiation therapy as appropriate per standard of care for patient's specific cancer)
3. Patients must be without evidence of residual disease as assessed by their treatment team
4. Patients must be either post-menopausal or surgically post-menopausal
5. Patients must be HLA-A2 positive
6. Patients must have a good performance status (ECOG\<2)

Exclusion Criteria:

1. HLA-A2 negative patients
2. Currently receiving immunosuppressive therapy to include chemotherapy, steroids, or methotrexate
3. In poor health (Karnofsky \<60%, ECOG \>2)
4. Total bilirubin \>1.5, creatinine \>2, hemoglobin \<10, platelets \<50,000, WBC \<2,000
5. Active pulmonary disease requiring medication to include multiple inhalers
6. Of child-bearing age with intact reproductive organs
7. Involved in other experimental protocols (except with permission of the other study PI)
8. History of autoimmune disease

Primary outcomes:
measure: Primary vaccination strategy
timeFrame: Six months after completion of primary vaccination series (month 12 of trial)
Secondary outcomes:
measure: Short-term immunity
timeFrame: One month after completion of primary vaccination series (month 7 of trial)
measure: Optimal booster inoculation strategy
timeFrame: Twelve months after completion of primary vaccination series (month 18 of trial)
measure: Delayed Type Hypersensitivity evaluation
timeFrame: Baseline to six months after completion of primary vaccination series (month 18 of trial)
Other outcomes:
Locations:
city: Houston
country: United States
facility: University of Texas M.D. Anderson Cancer Center
state: Texas
Study officials:
affiliation: Department of Breast Surgical Oncology, The University of Texas MD Anderson Cancer Center
name: Elizabeth Mittendorf, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vreeland TJ, Litton JK, Qiao N, Philips AV, Alatrash G, Hale DF, Jackson DO, Peace KM, Greene JM, Berry JS, Clifton GT, Peoples GE, Mittendorf EA. Phase Ib trial of folate binding protein (FBP)-derived peptide vaccines, E39 and an attenuated version, E39': An analysis of safety and immune response. Clin Immunol. 2018 Jul;192:6-13. doi: 10.1016/j.clim.2018.03.010. Epub 2018 Mar 21.