Trial Title:
Recombinant Human Endostatin Adenovirus Combined With Chemotherapy for Advanced Head and Neck Malignant Tumors
NCT ID:
NCT02283489
Condition:
Head and Neck Neoplasms
Conditions: Official terms:
Adenoviridae Infections
Neoplasms
Head and Neck Neoplasms
Paclitaxel
Endostatins
Conditions: Keywords:
Recombinant Human Endostatin Adenovirus
Head and Neck Malignant Tumor
clinical trial
randomized
Endostatin
gene therapy
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Unknown status
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
Double (Participant, Investigator)
Intervention:
Intervention type:
Drug
Intervention name:
recombinant human endostatin adenovirus
Description:
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.
Arm group label:
Combination therapy A
Arm group label:
Combination therapy B
Other name:
EDS01 (20140303)
Intervention type:
Drug
Intervention name:
Cisplatin injection
Description:
Specification: 2ml: 10mg. Usage: 25mg/m2, days 1 to 3, according to instruction.
Arm group label:
Chemotherapy
Arm group label:
Combination therapy A
Arm group label:
Combination therapy B
Intervention type:
Drug
Intervention name:
Paclitaxel injection
Description:
Specification: 5ml: 30mg. Usage: 160mg/m2 intravenously on day 1, according to
instruction.
Arm group label:
Chemotherapy
Arm group label:
Combination therapy A
Arm group label:
Combination therapy B
Summary:
This study will investigate the efficacy and safety of recombinant human endostatin
adenovirus combined with chemotherapy for advanced head and neck malignant tumors.
Detailed description:
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Advanced head and neck cancer unsuitable for surgery or radiotherapy (including head
and neck squamous carcinoma and nasopharyngeal carcinoma, which should not more than
30%)
- Cytological and/or histopathologic diagnosis
- Target lesions can be treated with intratumor injection
- Lesions can be measured by imaging with a diameter of ≥2 cm (RECIST1.1)
- No chemotherapy, radiotherapy, or biotherapy administered in the past 4 weeks
- Age of 18 to 70 years
- Life expectation of ≥12 weeks
- ECOG performance status of 0 to 2
- Laboratory examinations performed ≤7 days before enrollment with the following
results: absolute neutrophil count of ≥1.5 × 109 L-1, platelet count of ≥80 × 109/L,
total bilirubin level of ≤2 mg/dL, AST and ALT levels of ≤2 times the upper limit of
the reference range, and coagulation parameters ≤1.5 times the upper limit of the
reference range
- Voluntary participation and written informed consent
Exclusion Criteria:
- Allergy to EDS01
- Nerves and vessels passing through target lesions do not allow for injection of
EDS01 into lesions
- Simultaneous radiation of target lesions
- Cancer recurrence within 6 months treated by paclitaxel
- Severe coagulation dysfunction and bleeding tendency
- Serious medical diseases, myocardial infraction in the past 3 months, or acute
infection
- Currently pregnant or lactating
- Any conditions that the investigator regards as unsuitable for the study
Gender:
All
Minimum age:
18 Years
Maximum age:
70 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
West China Hospital, Sichuan University
Address:
City:
Chengdu
Zip:
610041
Country:
China
Status:
Recruiting
Contact:
Last name:
Liqun Zou, M.D.
Investigator:
Last name:
Liqun Zou, M.D.
Email:
Principal Investigator
Facility:
Name:
Sichuan Provincial People's Hospital
Address:
City:
Chengdu
Zip:
610072
Country:
China
Status:
Recruiting
Contact:
Last name:
Ke Xie, M.D.
Investigator:
Last name:
Ke Xie, M.D.
Email:
Principal Investigator
Facility:
Name:
Chongqing Cancer Hospital
Address:
City:
Chongqing
Zip:
400030
Country:
China
Status:
Recruiting
Contact:
Last name:
Xiaohong Zhou, M.D.
Investigator:
Last name:
Xiaohong Zhou, M.D.
Email:
Principal Investigator
Facility:
Name:
Shanghai Ninth People's Hospital Affiliated Shanghai JiaoTong University School of Medicine
Address:
City:
Shanghai
Zip:
200011
Country:
China
Status:
Recruiting
Contact:
Last name:
Wei Guo, M.D.
Investigator:
Last name:
Wei Guo, M.D.
Email:
Principal Investigator
Start date:
October 2014
Completion date:
October 2016
Lead sponsor:
Agency:
Renmiao Zhang
Agency class:
Industry
Collaborator:
Agency:
West China Hospital
Agency class:
Other
Source:
Chengdu Shi Endor Biological Engineering Technology Co., Ltd
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT02283489
