Table 2 Clinical trials of survivin-targeting therapies

UMIN000000976

University Hospital Medical Information Network

Oral cancer

Study to evaluate the safety and the efficacy of survivin-2B80-88 peptide vaccination in HLA-A24-positive patients with advanced or recurrent oral cancer.

Biological: Survivin-2B80-88 peptide vaccination

1) Safety

2) Efficacy

Phase 1/Completed: survivin-2B peptide vaccination was safe and had therapeutic potential for oral cancer patients

Sept 1, 2003

Feb 01, 2011

NCT01250470

Roswell Park Cancer Institute

Malignant glioma

Study the side effects of survivin peptide vaccine therapy when given together with sargramostim in treating patients with malignant glioma.

Other: Laboratory Biomarker Analysis

Drug: Montanide ISA-51/Survivin Peptide Vaccine

Biological: Sargramostim

1) Safety and toxicity

2) Immune response

Phase I/Completed

Nov 24, 2010

Feb 24, 2017

NCT02851056

H. Lee Moffitt Cancer Center and Research Institute

Multiple Myeloma

Test the safety and immune responses of a new survivin vaccine and its effects on multiple myeloma cancer, when administered before and after their autologous hematopoietic cell transplant (HCT). The name of the vaccine is called Dendritic Cell Survivin Vaccine (DC: AdmS)

Biological: Survivin Vaccine

Procedure: Autologous Hematopoietic Cell Transplantation

Biological: Prevnar 13

Drug: Granulocyte-colony Stimulating Factor

1) Safety of DC: AdmS when administered to patients with myeloma before and at day +21 after autologous hematopoietic stem cell transplant.

2) The ability of DC: AdmS to induce T cell immune responses against survivin when administered to patients with myeloma

Recruiting

July 28, 2016

Dec 7, 2016

NCT00108875

Malignant Melanoma Pancreatic Cancer, Colon, Cancer, Cervical Cancer

Evaluates the safety, the immunological response and the clinical outcome of a vaccination with survivin peptides for patients with advanced melanoma, pancreatic, colon and cervical carcinoma.

Biological: Survivin peptide vaccine

1) Progression-free survival, Overall survival, Immunological response

2) Best response

Phase 1

Phase 2/Unknown

April 19, 2005

July 27, 2006

NCT00961844

Oslo University Hospital

Metastatic Malignant Melanoma

Study the safety and effectiveness of chemotherapy with immunotherapy by giving the patients Temozolomide, before vaccination. The investigators have also included hTERT and survivin mRNA in the vaccine. Finally, the investigators want to introduce ex vivo T cell expansion after lymphodepletion for the patients who show an immune response.

Biological: Dendritic cells - transfected with hTERT-, survivin- and tumor cell derived mRNA + ex vivo T cell expansion and reinfusion

Drug: Temozolomide

1) Safety and toxicity of vaccination with DC transfected h-TERT mRNA, survivin mRNA and tumor cell mRNA.

2) Evaluation of immunological responses, time to disease progression and survival time

Phase 1

Phase 2/Terminated

Aug 12, 2009

Aug 2014

NCT00573495

University of Pennsylvania

Breast Cancer

Study on how to activate the immune system with a vaccine, which made up of two proteins found in breast cancer: telomerase and survivin.

Biological: hTERT/Survivin Multi-Peptide Vaccine

1) Safety

2) Immunologic response

Phase 1/Completed

Dec 12, 2007

Sept 27, 2016

NCT00074230

University Hospital Erlangen

Melanoma (Skin)

Study the effectiveness of vaccine therapy using autologous dendritic cells with antigens in treating patients with stage IV cutaneous melanoma.

Biological: Autologous Dendritic Cells loaded with MAGE-A3, MelanA and Survivin

1) Safety and tolerability, overall survival.

2) Immune response and disease progression

Phase 1

Phase 2/Completed

Dec 10, 2003

May 11, 2015

NCT02323230

ImmunoVaccine Technologies, Inc.

Diffuse Large B-Cell Lymphoma

Assess the efficacy and safety of DPX-Survivac plus low dose cyclophosphamide in subjects with recurrent diffuse large B-cell lymphoma (DLBCL) who are not eligible for transplant.

Biological: DPX-Survivac

Drug: Cyclophosphamide

1) Objective response rate

2) Immune response and levels of cell mediated immunity targeting the survivin epitopes

Phase 2/Recruiting

Dec 12, 2014

Dec 14, 2015

NCT01416038

ImmunoVaccine Technologies, Inc.

Ovarian Cancer

Fallopian Tube Cancer

Peritoneal Cancer

Determine the safety and immunogenicity profiles of DPX-Survivac, a therapeutic vaccine co-administered with a regimen of low dose oral cyclophosphamide.

Biological: DPX-Survivac

Drug: low dose cyclophosphamide (oral)

1) Number of reported adverse events and Progression free survival

2) Levels of cell mediated immunity targeting the survivin epitopes

Phase 1

Phase 2

Aug 9, 2011

Dec 14, 2015

NCT02688673, NCT02693236, NCT01924156

Affiliated Hospital to Academy of Military Medical Sciences

Small- Cell Lung Cancer, Esophagus Cancer, Renal Cell Carcinoma

Evaluate the safety and efficacy of dendritic cells (DC) combined with cytokine-induced killer (CIK) cells to treat cancer patients

Biological: adenovirus-transfected autologous DC vaccine plus CIK cells

1) Objective rate response (CR + PR) as measured by RECIST criteria

2) Number of participants with adverse events

Phase 1

Phase 2/Ongoing

2013-2016

2016

NCT00537121

Roswell Park Cancer Institute

Esophageal Cancer, Gastric Cancer, Liver Cancer

Study the side effects and best dose of vorinostat (SAHA) when given together with irinotecan, fluorouracil, and leucovorin in treating patients with advanced upper gastrointestinal cancer. SAHA suppresses tumor cells growth by blocking HDAC that also involve inhibition survivin and TGF-beta signaling.

Drug: fluorouracil

Drug: irinotecan hydrochloride

Drug: leucovorin calcium

Drug: vorinostat

Other: pharmacological study

1) Maximum tolerated dose (MTD) of vorinostat (SAHA) when administered continuously and intermittently with standard doses of irinotecan hydrochloride, fluorouracil, and leucovorin calcium (FOLFIRI). Recommended phase II dose (RPTD) of SAHA when administered continuously and intermittently with standard doses of FOLFIRI

2) Toxicity of the SAHA and FOLFIRI combination. Effects of SAHA and FOLFIRI combination on TGF-β signaling and survivin expression. Response rate. Progression-free survival Overall survival

Phase 1/Completed

Sept 27, 2007

June 26, 2013

NCT01398462

JW Pharmaceutical

Acute Myeloid Leukemia, Chronic Myelomonocytic Leukemia, Myelodysplastic Syndrome Myelofibrosis

Test safety, efficacy, and antitumor activity of CWP232291. This drug targets beta-catenin for degradation and thereby inhibits the expression of cell cycle and anti-apoptotic genes such as cyclin D1 and survivin

Drug: CWP232291

1) To determine Maximum Tolerated Dose (MTD)and dose limiting toxicities (DLTs)

2) Pharmacokinetics, and assess the anti-tumor activity

Phase 1

July 17, 2011

March 7, 2016

NCT00664586

Erimos Pharmaceuticals

Refractory Solid Tumors

Lymphoma

Continuous infusion study designed to explore if constant concentration over time adds to the effectiveness of terameprocol without increasing toxicity. It will also explore weekly dosing as an option.

Drug: Terameprocol (EM-1421)

1) To determine Maximum Tolerated Dose (MTD)and dose limiting toxicities (DLTs)

2) Assess the anti-tumor activity

Phase 1/Terminated due to funding constraints

April 21, 2008

Feb 20, 2016

NCT00664677

Erimos Pharmaceuticals

Leukemias:

AML, ALL, ATL, CML-BP, CLL, MDS, CMML

Determine the safety, maximum tolerated dose,dose limiting toxicity of Terameprocol and determine the pharmacokinetics of Terameprocol given as intravenous infusion.

Drug: Terameprocol (EM-1421)

1) To determine Maximum Tolerated Dose (MTD)and dose limiting toxicities (DLTs)

2) Pharmacokinetics and assess the anti-tumor activity

Phase 1/Terminated due to funding constraints

April 21, 2008

Feb 20, 2016

[223]

H. Lee Moffitt Cancer Center

Advanced solid malignancies or lymphoma

Determine the maximum-tolerated dose (MTD) and assess the safety, pharmacokinetics, and preliminary evidence of antitumor activity

Drug: YM155

(First human trial)

1) To determine Maximum Tolerated Dose (MTD) and dose limiting toxicities (DLTs)

2) Pharmacokinetics of drug and preliminary evidence of 2anticancer activity

Phase 1/Completed: Drug is safe to administer with no severe toxicities, and showed antitumor activity

Nov 10, 2008

[224]

National Cancer Institute

Advanced non–small-cell lung cancer (NSCLC).

Evaluate the antitumor activity and safety of YM155, a novel, small-molecule suppressor of survivin, as single-agent therapy.

Drug: YM155

1) Safety and tolerance

2) Anti-tumor activity

Phase 2/Completed: Drug showed modest single-agent anti-tumor activity, and a favorable safety/tolerability profile was reported

Sept 20, 2009

[226]

Georgetown University Hospital

Refractory diffuse large B-cell lymphoma

Study toxicity and efficacy YM155

Drug: YM155

1) Safety and tolerance

2) Anti-tumor activity

Phase 2/Completed: Drug was well tolerated and showed limited anti-tumor activity as a single agent

June 15, 2012

NCT00514267

Astellas Pharma Inc

Prostate Cancer

Tumors

Determine the feasibility and safety of administering YM155 in combination with docetaxel

Drug: YM 155

Drug: Docetaxel

Drug: Prednisone

1) Occurrence of dose limiting toxicities

2) Assessment of safety, efficacy and pharmacokinetics

Phase 1

Phase 2/Completed

Aug 7, 2007

July 23, 2015

NCT01100931

National Cancer Institute

NSCLC

Solid Tumors

Determine the efficacy of the combination of carboplatin, paclitaxel, and YM155 in the treatment of non-small-cell lung cancer

Drug: YM155

Drug: Carboplatin

Drug: Paclitaxel

1) Assessment of safety, efficacy and pharmacokinetics

2) Anti-tumor activity

Phase 1

Phase 2/Completed

April 8, 2010

Sept 29, 2015

NCT00315653

Fujirebio Diagnostics, Inc.

Bladder Cancer

Evaluate the ability of urinary Survivin mRNA measurement to estimate the risk of bladder cancer at the time of cystoscopy in subjects with no prior history of bladder cancer presenting with microscopic or macroscopic hematuria

Procedure: Urine Sampling

Evaluation of the Survivin Urine mRNA Assay

Completed

April 18, 2006

March 12, 2008

NCT02016833

PX Biosolutions

Ovarian Serous Adenocarcinoma, Undifferentiated Carcinoma of Ovary, Cervical Cancer, Cervical Intraepithelial Neoplasia, Grade 3

Acute Myeloid Leukemia, Chronic Myeloid Leukemia

Establishing immunological assays for the qualitative and quantitative evaluation of WT-1, Survivin and HPV16 E7-specific immune responses in cancer patients

Procedure: Blood Sampling

Development and validation of ELISpot and tetramer assays

Completed

Dec 5, 2013

April 29, 2015