Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Digestive System Diseases

Rare Diseases

Carcinoma

Prostatic Neoplasms

Carcinoma, Hepatocellular

Glioma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Neuroepithelioma

proton therapy

Ji-Hong Hong, Ph.D.

The main purpose of this study is to collect the safety data of Sumitomo Heavy Industries' proton therapy equipment for the treatment of solid cancer patients in Linkou Chang Gung Memorial Hospital, including the patients' early-stage adverse reactions and the efficacy on tumors, as well as to assess the operating functionality of the proton therapy system.

The main purpose of this study is to collect the safety data of Sumitomo Heavy Industries' proton therapy equipment for the treatment of solid cancer patients in Linkou Chang Gung Memorial Hospital, including the patients' early-stage adverse reactions and the efficacy on tumors, as well as to assess the operating functionality of the proton therapy system.

In this study, solid cancer subjects will be treated with Sumitomo's proton therapy system. Safety and operating functionality data will be collected during the treatment and following-up.

Early-Phase Safety of Proton Therapy Equipment

A Study of the Early-Phase Safety of Proton Therapy Equipment for Patients Suffering From Solid Cancers, and the Equipment's Operational Effectiveness.

After enrollment, each patient has to receive physical examination, laboratory tests, and image studies as baseline. During the course of radiotherapy, patients will have weekly evaluations in physicals and laboratory tests. Image studies are optional during treatment. In the follow-up periods, monthly exams, including regular physicals, markers in serum and urine and image studies to evaluation treatment responses, will be scheduled till 90 days after the end of treatment.

During treatment, the frequency of operation of the system error will be recorded and analyzed to see if the system can run smoothly.

Response Evaluation Criteria In Solid Tumors:(1)complete Response(CR),Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \<10 mm (2)Partial Response(PR), At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. (3)Progressive Disease(PD), At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (4)Stable Disease(SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. (5) Inevaluable (NE), Inevaluable for response: specify reasons (for example: early death, malignant disease; toxicity; tumor assessments not repeated/incomplete; other (specify).

Chang Gung Memorial Hospital

proton therapy

proton therapy: proton therapy

Safety

Age, Continuous

Gender

Hong, Ji-Hong M.D.

Rate and Severity of Adverse Reactions

6 subjects received a total of 165 proton therapy, a total of 21 times the system running abnormalities. There was no correlation between system abnormalities during the study and the adverse events.

The Frequency of Operation of the System Error

Percentage of System Errors

Stable Disease(SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

Stable Disease

Partial Response(PR), At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Partial Response

Inevaluable (NE), Inevaluable for response: specify reasons (for example: early death, malignant disease; toxicity; tumor assessments not repeated/incomplete; other (specify).

Inevaluable

Percentage of Each Target Lesion Evaluation Types.(1)Complete Response(2)Partial Response,(3)Progressive Disease,(4)Stable Disease,(5) Inevaluable

Overall Study

Infections

Symptoms and General Pathology

Head and Neck Neoplasms

Adenoviridae Infections

Communicable Diseases

Virus Diseases

DNA Virus Infections

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Albumin-Bound Paclitaxel

Cisplatin

Endostatins

Tubulin Modulators

Antimitotic Agents

Angiogenesis Inhibitors

Growth Inhibitors

Recombinant human endostatin adenovirus (EDS01), 5.0 × 1011 VP intratumorally on days 0 and 7; paclitaxel, 160 mg/m2 intravenously on day 1; cisplatin, 25 mg/m2 intravenously on days 1 to 3.

Recombinant human endostatin adenovirus (EDS01), 1.0 × 1012 VP intratumorally on days 0 and 7; paclitaxel, 160 mg/m2 intravenously on day 1; cisplatin, 25 mg/m2 intravenously on days 1 to 3.

Paclitaxel, 160 mg/m2 intravenously on day 1; cisplatin, 25 mg/m2 intravenously on days 1 to 3.

Specification: 1mL/division, 1.0×1012 virus particle (VP). ESD01 preparation: Thaw at room temperature, dilute with normal saline to required volume (no more than 2 mL).

Method of administration: Intratumor injection, once a week for 2 weeks, every 3 weeks for one cycle. Select only one target lesion even when lesions are present. The target lesion is the largest and easiest to inject. This will be fixed during the study.

recombinant human endostatin adenovirus

Specification: 2ml: 10mg. Usage: 25mg/m2, days 1 to 3, according to instruction.

Cisplatin injection

Specification: 5ml: 30mg. Usage: 160mg/m2 intravenously on day 1, according to instruction.

Paclitaxel injection

Renmiao Zhang

Liqun Zou, M.D.

Ke Xie, M.D.

Xiaohong Zhou, M.D.

Wei Guo, M.D.

Renmiao Zhang, MD, PhD

This study will investigate the efficacy and safety of recombinant human endostatin adenovirus combined with chemotherapy for advanced head and neck malignant tumors.

Head and neck cancer is one of the most common malignant tumors in China, accounting for 19.9% to 30.2% of malignant tumors in this country. Approximately 60% to 70% of patients have stage III or IV disease at the time of diagnosis, and the 5-year overall survival is about 30%. The local recurrence rate ranges from 50% to 60%. The 5-year overall survival for patients treated with multidisciplinary treatment, which is a common treatment method that includes surgery, chemotherapy, radiotherapy, and biotherapy, has recently increased by 5%. Further improvements in the treatment effects of head and neck cancer are required.

Endostatin, an endogenous angiogenesis inhibitor and a C-terminal fragment of collagen XVIII, effectively inhibits tumor angiogenesis by specific inhibition of neovascular endothelial cells \[7, 8\]. Its characteristic antitumor effect is dose-dependent, requiring continuous high protein activity. Transportation of recombinant genes with adenovirus vectors into the body leads to continuous expression of high levels of endogenous secretory proteins, resolving the limitation of foreign protein infusion. Previous studies have shown that the antitumor activity of recombinant human endostatin adenovirus is higher than that of recombinant human endostatin protein.

EDS01, an antitumor gene therapy product that uses recombined adenovirus type 5 as the vector for the human endostatin gene, may be termed a recombinant adenovirus-recombined human endostatin gene. Intratumor injection of EDS01 reportedly results in transportation of the human endostatin gene into tumor cells by adenovirus infection, leading to the expression of endostatin protein. Expression of this protein inhibits neovascular endothelial cells, neovascularization, and tumor growth and metastasis. Both in vivo and in vitro experiments have shown that EDS01 significantly inhibits the growth of neovascular endothelial cells and tumor growth in nude mouse xenograft models of laryngocarcinoma and nasopharyngeal carcinoma.

A phase I clinical trial (No. treatment effect) conducted at West China Hospital of Sichuan University enrolled patients with superficial advanced head and neck cancer lesions. The patients underwent injection of different doses of EDS01, and the investigators performed a preliminary evaluation of the maximally tolerated dose and adverse events. The study showed that, whether administered by dose escalation or in multiple doses, EDS01 was well tolerated without dose-limiting toxicity and maximum tolerated dose. The main side effects were fever and injection site pain with flu-like symptoms. A small amount of EDS01 (1/10 000 000) was absorbed into the bloodstream. A thimbleful (1/100 000 000 to 1/10 000 000 000) was excreted in the urine and feces and was nontoxic to the environment. The target lesions exhibited a treatment response.

According to the results of this phase I trial, both 5.0 × 1011 and 1.0 × 1012 virus particles (VP) of EDS01 showed adequate safety and treatment responses. Therefore, in the subsequent phase II clinical trial, the optimal of these two doses will be determined. The treatment effects and safety of this protocol for head and neck cancer will also be further investigated.

In summary, this study will initially explore the efficacy and safety of recombinant human endostatin adenovirus combined with chemotherapy for advanced head and neck malignant tumors.

In the experimental group, the target lesion is defined as that injected by EDS01. In the control group, the target lesion is defined as that selected at the inception.

Recombinant Human Endostatin Adenovirus Combined With Chemotherapy for Advanced Head and Neck Malignant Tumors

Recombinant Human Endostatin Adenovirus Combined With Chemotherapy for Advanced Head and Neck Malignant Tumors: Phase II, Multicenter, Randomized, Controlled Clinical Trial

Only the leading center will be tested for environmental pollution. This testing will include evaluation of swab specimens, urine specimens, and fecal specimens before the first administration and immediately, 24 hours, and 3 days after the first administration. Specimens will be taken from injection sites and the oropharynx and stored at -80 °C for testing. Urine specimens (2 mL) will be gathered at different times and mixed, then stored at -80 °C for testing. Feces will be gathered in tubes, mixed with 2 mL of normal saline, stirred for 5 minutes, and centrifuged at 2 000 r/min for 10 minutes; the supernatant will be stored at -80 °C for testing.

Laboratory examination: complete blood count, routine urinalysis, routine fecal test, liver function, renal function, and electrolytes. Coagulation tests will be performed on the first day of the first cycle.

Objective response rate (ORR) of target lesion is defined as the percentage of subjects with evidence of a confirmed complete response (CR) or partial response (PR), , determined by tumor assessments from radiological tests including CT and MRI. CR is defined as disappearance of the target lesion. PR is defined as a decrease of at least 30% in the product of two perpendicular diameters of the target lesion.

The disease control rate of the target lesion includes CR, PR, and stable disease (SD). SD is defined as a decrease of \<30% or an increase of \<20% in the size of the target lesion, determined by tumor assessments from radiological tests including CT and MRI.

All lesions include the target lesions, nontarget lesions, and new lesions. ORR of all lesions includes CR and PR.

Time to progression is defined as the time from randomization until objective tumor progression as verified for the first time.

Serum IgG antibody responses to the respective viruses will be detected in blood samples. ELISA will be used to test the quantity of serum IgG in a central laboratory according to the specific provisions of the central laboratory. During the screening phase and on days 7, 21, 35, 48, 62, and 76, venous serum (3 mL) will be gathered in a drying tube by venipuncture. After 30 minutes, they will be centrifuged at 2 000 r/min for 10 minutes, and the supernatant will be stored at -80 °C for testing.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Early-Phase Safety of Proton Therapy Equipment	NCT02315989	Malignant Gliom... Hepatocellular ... Head and Neck M... Prostate Cancer	proton therapy	20 Years - 75 Years	Chang Gung Memorial Hospital
Early-Phase Safety of Proton Therapy Equipment	NCT02315989	Malignant Gliom... Hepatocellular ... Head and Neck M... Prostate Cancer	proton therapy	20 Years - 75 Years	Chang Gung Memorial Hospital
Recombinant Human Endostatin Adenovirus Combined With Chemotherapy for Advanced Head and Neck Malignant Tumors	NCT02283489	Head and Neck N...	recombinant hum... Cisplatin injec... Paclitaxel inje...	18 Years - 70 Years	Chengdu Shi Endor Biological Engineering Technology Co., Ltd
Recombinant Human Endostatin Adenovirus Combined With Chemotherapy for Advanced Head and Neck Malignant Tumors	NCT02283489	Head and Neck N...	recombinant hum... Cisplatin injec... Paclitaxel inje...	18 Years - 70 Years	Chengdu Shi Endor Biological Engineering Technology Co., Ltd

Spots Global Cancer Trial Database for head and neck malignant tumor