Glioblastoma Clinical Trial
Official title:
A Phase I Clinical Trial of mTOR Inhibition With Rapamycin for Enhancing Intranodal Dendritic Cell Vaccine Induced Anti-tumor Immunity in Patients With NY-ESO-1 Expressing Solid Tumors
This phase I trial studies the side effects and best schedule of vaccine therapy with or without sirolimus in treating patients with cancer-testis antigen (NY-ESO-1) expressing solid tumors. Biological therapies, such as sirolimus, may stimulate the immune system in different ways and stop tumor cells from growing. Vaccines made from a person's white blood cells mixed with tumor proteins may help the body build an effective immune response to kill tumor cells that express NY-ESO-1. Infusing the vaccine directly into a lymph node may cause a stronger immune response and kill more tumor cells. It is not yet known whether vaccine therapy works better when given with or without sirolimus in treating solid tumors.
| Status | Completed |
| Enrollment | 18 |
| Est. completion date | July 2016 |
| Est. primary completion date | July 2016 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 18 Years and older |
| Eligibility |
Inclusion Criteria: - Patients with any solid tumors at high risk of recurrence or with minimal residual disease; there may or may not be measurable or symptomatic disease (i.e., patients with bladder, brain, breast, esophageal, gastrointestinal, hepatocellular, kidney, lungs, melanoma, ovarian, prostate, sarcomas, and uterine) - Cancer types: - Prostate cancer: patients with metastatic, castrate refractory prostate cancer; the use of luteinizing hormone-releasing hormone (LHRH) agonist is allowed - Kidney cancer: patients with metastatic kidney cancer; prior therapies with cytokines, vascular endothelial growth factor (VEGF) and mechanistic target of rapamycin (serine/threonine kinase) (mTOR) inhibitors are allowed - Bladder cancer: patients with metastatic urothelial carcinoma; prior cisplatin-based therapies are allowed - Ovarian cancer: eligible patients may have asymptomatic residual measurable disease on physical examination and/or computed tomography (CT) scan, and/or may have an elevated cancer antigen (CA)-125; or may be in complete clinical remission after treatment for primary or recurrent disease - Brain tumors: histologic proof of one of the following: glioblastoma multiforme, anaplastic astrocytoma, anaplastic oligodendroglioma or anaplastic mixed glioma or anaplastic oligoastrocytoma; patients who have had recent cranial surgery are eligible for inclusion, but the vaccine may not be administered prior to postoperative day 14 - Uterine cancer: patients with advanced (stages II-IV) or recurrent disease who have completed standard therapy, currently no evidence of disease (NED) or with minimal residual disease; patients with stage I uterine serous carcinomas or sarcomas are also eligible after completion of standard therapy - Breast cancer: patients can enter study after completion of all chemotherapy (including trastuzumab), radiation, and breast/axillary surgery; patients may participate while on endocrine therapy; stages I-III patients with the following characteristics: - Estrogen-receptor (ER) negative with positive lymph nodes; ER negative with negative nodes if tumor > 2 cm; ER positive with positive lymph nodes; and ER positive with negative lymph nodes and tumor > 5 cm - Sarcomas: patients with sarcomas of any site, who have completed standard therapy, and are in remission, or have minimal disease burden - Lungs: resected patients with hilar or ipsilateral mediastinal nodal disease (i.e., a subset of patients with stage II and IIIA disease); and patients with residual disease on imaging after definitive radiation or chemoradiation therapy - Esophageal: resected patients with any nodal (i.e., thoracic or abdominal) disease; and patients with residual disease on imaging after definitive chemoradiation therapy - Melanoma: stage IIB, stage IIC, and stage III who have completed planned definitive therapy for their disease including radiotherapy and/or interferon; patients declining interferon or with contra-indications to interferon will also be eligible provided they meet requisite criteria for this study (i.e., non-measurable disease); stage IV melanoma of M1a sub-type only, who are not candidates for additional therapy of curative potential (i.e., small volume disease; may be measurable or evaluable); and stage IV melanoma, NED, status post (s/p) complete resection of known sites of disease (i.e., non-measurable disease) - Hepatocellular carcinoma (HCC): patients who have been treated with surgical resection for HCC; and following chemoembolization as adjuvant therapy for HCC - Gastrointestinal: patients who have completed standard therapies for gastric and colorectal cancers, and deemed to be at high-risk of relapse - Any human leukocyte antigen (HLA) type; historic HLA typing is permitted - Tumor expression of NY-ESO-1 or LAGE-1 by immunohistochemistry (IHC) and/or reverse transcription polymerase chain reaction (RTPCR) - Life expectancy > 6 months - Absolute neutrophil count (ANC) >= 1,000/uL - Platelets (PLT) >= 75,000/uL - Hemoglobin (Hgb) >= 8 g/dL - Total bilirubin =< 1.5 x upper limit of normal (ULN) - Serum aspartate aminotransferase (serum glutamic oxaloacetic transaminase [SGOT]/aspartate aminotransferase [AST]) or serum alanine aminotransferase (serum glutamate pyruvate transaminase [SGPT]/alanine aminotransferase [ALT]) =< 3 x ULN - Serum creatinine =< 2 x ULN - Prothrombin time (PT)/international normalized ratio (INR) =< 1.5 x ULN; patients receiving anticoagulation therapy, PT/INR =< 3 - Pulmonary function tests: forced expiratory volume in one second (FEV1) > 50% and diffusion capacity of the lungs for carbon monoxide (DLCO) > 50% - Pulse oximetry: oxygen (O2) saturation >= 90% on room air - Electrocardiogram, showing no clinical significant or acute abnormality - Have been informed of other treatment options - Patient or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure - Have an Eastern Cooperative Oncology Group (ECOG) performance status of =< 2 - Patients of child-bearing potential must agree to use acceptable contraceptive methods (e.g., double barrier) during treatment Exclusion Criteria: - Metastatic disease to the central nervous system for which other therapeutic options, including radiotherapy, may be available - Other serious illnesses (e.g., serious infections requiring antibiotics, bleeding disorders) - History of severe autoimmune disorders requiring use of steroids or other immunosuppressives - Concomitant systemic treatment with corticosteroids, anti-histamine or non-steroidal anti-inflammatory drugs, aspirin > 325 mg; specific cyclooxygenase (COX)-2 inhibitors are permitted - Chemotherapy, radiation therapy, or immunotherapy within 4 weeks prior to first dosing of study agent (6 weeks for nitrosoureas); concomitant hormonal therapies for breast and prostate cancers are allowed - Clinically significant heart disease (New York Heart Association [NYHA] class III or IV) within 6 months - Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study - Lack of availability of a patient for immunological and clinical follow-up assessment - Known pulmonary hypertension - Known hypersensitivity to sirolimus - Evidence of current drug or alcohol abuse or psychiatric impairment, which in the investigator's opinion will prevent completion of the protocol therapy or follow-up - Pregnant or nursing female patients - Unwilling or unable to follow protocol requirements - Any condition which in the investigator's opinion deems the patient an unsuitable candidate to receive study drug; (i.e., any significant medical illness or abnormal laboratory finding that would, in the investigator's judgment, increase the subject's risk by participating in this study) - Received an investigational agent within 30 days prior to enrollment - Known hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) |
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| United States | Roswell Park Cancer Institute | Buffalo | New York |
| Lead Sponsor | Collaborator |
|---|---|
| Roswell Park Cancer Institute | National Cancer Institute (NCI) |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Other | Time to disease progression | Up to 12 months post treatment | No | |
| Primary | Incidence of adverse events in patients receiving the DEC-205/NY-ESO-1 fusion protein CDX-1401 with and without sirolimus, as evaluated according to the NCI CTCAE scale version 4.0 | The safe schedule of the combinatorial regimen is established at the dose before 2/6 patients experience dose-limiting toxicity. Estimated using a one-sided, 95%, exact binomial confidence interval (Clopper-Pearson). | Up to 12 months post-treatment | Yes |
| Secondary | NY-ESO-1 specific cellular immunity | Analyzed via an analysis-of-covariance (ANCOVA) model with post-treatment levels modeled as a function pretreatment levels and main effects corresponding to the 3 + 3 design. | Up to 12 months post-treatment | No |
| Secondary | NY-ESO-1 specific humoral immunity | ANCOVA model with post-treatment levels modeled as a function pretreatment levels and main effects corresponding to the 3 + 3 design. | Up to 12 months post-treatment | No |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
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