Head and Neck NeoplasmsPhase 3NCT02630264
E10A for the Treatment of Squamous Cell Carcinoma of the Head and Neck
A Phase 3 study testing Endostatins, Paclitaxel injection and Cisplatin injection in people with Head and Neck Neoplasms, run by Guangzhou Double Bioproducts Co., Ltd at 1 site in China.
Trial summary
Recombinant human endostatin adenovirus injection is a novel anti-tumor gene therapy drug. E10A contains a recombinant human endostatin gene with the second-generation recombinant adenovirus as its vector. After transfection tumor cells. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Head and Neck Neoplasms
- What is being tested?
- Endostatins, Paclitaxel injection and Cisplatin injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 540 participants
- Where
- 1 siteChina
- Study dates
- Jun 2013to Dec 2016
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients older than 18 years with histologically or cytologically proven locoregionally advanced or metastatic HNSCC (excluding NPC) not suitable for operation or radiotherapy
- A life expectancy≧12 weeks.
- Patients were required to have at least one measurable (by imaging or photograph complied RECIST) lesion with the largest diameter ≧2 cm and suitable for the intratumoral injection of E10A,
- Not received chemotherapy, radiotherapy, or biotherapy within 4 weeks.
- Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0-2.
- Adequate bone marrow,renal, and liver functions.
Who cannot join
- Known allergies to the study drug.
- The presence of important blood vessels/nerves or ulceration in the target lesion not suitable for injection.
- Tumor relapses within 6 months after paclitaxel chemotherapy.
- Severe coagulation disorders or bleeding tendency.
- Severe uncontrolled medical conditions.
- Recent history of myocardial infarction acute infection, pregnancy or lactation, or symptomatic brain metastases
- A history of corticosteroids or immunosuppressives use within four weeks of study entry
- Received any chemotherapy or radiotherapy within four weeks of study entry
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Guangzhou DB
Gaungzhou, Guangdong, 510663
Chao Zhang, georgezhang2015@sina.com
About this study
Official title: A Randomized, Open-label, Multi-center Phase III Study Designed to Evaluate the Safety and Efficacy of E10A in Patients With Recurrent/Unresectable Squamous Cell Carcinoma of the Head and Neck Region
Recombinant human endostatin adenovirus injection is a novel anti-tumor gene therapy drug. E10A contains a recombinant human endostatin gene with the second-generation recombinant adenovirus as its vector. After transfection tumor cells. E10A expresses human endostatin, which inhibits vascular endothelial cell proliferation and tumor angiogenesis, and blocks tumor blood supply, thereby specifically inhibiting tumor growth and inducing apoposis of tumor cells. Both pre-clinical and animal models have demonstrated the anti-tumor activities of E10A. The safety and efficacy of E10A in treating head and neck cancer has also been demonstrated in Phase I and Phase II studies.
Read the detailed description
Phase II Clinical Study From March 2008 to December 2010 Safety and efficacy of intratumoral injections of E10A to cisplatin and paclitaxel was evaluated a multicenter, open-label, randomized clinical study in patients with advanced head and neck squamous cell carcinoma.
136 eligible patients were recruited and randomly assigned. Patients with locally advanced or metastatic head and neck squamous cell carcinoma or nasopharyngeal carcinoma not suitable for operation or radiotherapy were randomly assigned to receive E10A plus chemotherapy every 21 for a maximum of six cycles or to receive chemotherapy only.
The primary end point was the objective response rate (RR), defined as the proportion of patients who had a complete response (CR) or partial response (PR) at the target tumor lesion. The secondary end points were the objective disease control rate (DCR, or stable disease (SD) + PR + CR at the target tumor lesion), the overall RR, the overall DCR, OS, and progression-free survival (PFS).
The administration of E10A benefited some subgroups of patients. In the HNSCC patients, the objective RR was 36.5% (15/41) with E10A administration, exhibiting a trend of exceeding the rate of 20.0% (7/35) in the control group (P = 0.090; OR: 0.43), whereas the objective RR was 44.4% (12/27) versus 40.6% (13/32) in the NPC patients (P = 0.487; OR: 0.86). Patients who had previously received chemotherapy in the E10A group had a 44.8% (12/29) objective RR, whereas patients in the control group had only a 22.6% objective RR (7/31; P = 0.06, OR: 0.36). In contrast, patients without previous chemotherapy had a similar RR in both groups (34.3 versus 39.4%; P = 0.426, OR: 1.25).
The difference in the Kaplan-Meier estimates of PFS favored chemotherapy plus E10A, which resulted in a 3.43-month improvement. With a median follow-up of 10.47 months, the median PFS was 3.60 months (interquartile range: 2.60-7.63) in the control group and 7.03 months (interquartile range: 3.27-13.73) in the E10A group. As The median PFS was 3.60 months (interquartile range: 2.60-7.63) in the control group and 7.03months (interquartile range: 3.27-13.73) in the E10A group.
The OS of the E10A group was relatively prolonged in different subgroups compared with the controls (e.g., 13.37 months versus 9.67 months in the HNSCC patients, 13.03 months versus 10.50 months in those who had received prior treatment; Figure 1), but these results did not translate into significantly superior survival.
- Conditions
- Head and Neck Neoplasms
- Being tested
- Endostatins, Paclitaxel injection, Cisplatin injection
- Keywords
- clinical trial, Recombinant Human Endostatin Adenovirus, randomized
- Medical subject headings
- Head and Neck Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EndostatinsDrug
Also called E10A
Specification: 1mL/division, 1×1012 VP/1.0mL
E10A preparation:
- Thaw frozen E10A stored at -20°C vials at room temperature until E10A is liquid.
- Swirl gently. Do NOT shake.
Method of administration
- E10A was diluted with 0.9% sodium chloride to appropriate dose according to the longest diameter of the target lesion.
- After local anesthesia, we penetrated the syringe under normal skin subcutaneously 5 mm into the tumor or vertically into the lymph node under direct visualization and withdrew it to confirm the absence of blood.
- Applied local compression for 10 minutes and pasted a sterile sticker on the injection site to avoid bleeding.
Paclitaxel injectionDrug
Specification:
30mg/5mL,
Usage:
160mg/m2 on day 3, according to instruction.
Cisplatin injectionDrug
Specification:
20mg
Usage:
Cisplatin 25mg/ m2 on day 3, 4, and 5,according to instruction.
| Study group | Role | What they receive |
|---|---|---|
| Combination therapy | Experimental | E10A+chemotherapy group (360 subjects):
1. E10A (Endostatins) of 1.0×1012VP on day 1 and 6
2. Paclitaxel Injection 160mg/m2 on day 3
3. Cisplatin Injection 25mg/m2 on day 3, 4, and 5. Repeat every 21 days. Receives: Drug: Endostatins; Drug: Paclitaxel injection; Drug: Cisplatin injection |
| Chemotherapy | Experimental | Chemotherapy-alone group (180 subjects):
1. Paclitaxel Injection 160mg/m2 on day 1
2. Cisplatin Injection 25mg/m2 on day 1, 2, and 3. Repeat every 21 days Receives: Drug: Paclitaxel injection; Drug: Cisplatin injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to progression
Time to progression is defined as the time from randomization until objective tumor progression as verified for the first time
Measured: Up to 24 weeks
Secondary outcomes (4)
Change in Overall response rate (CR+PR)
the end of every 2 treatment cycles (each cycle is 21 days), and every 3 months during follow-up until disease progression. objective response rate (RR), defined as the proportion of patients who had a complete response (CR) or partial response (PR) at the target tumor lesion.
Measured: Up to 24 weeks, from date of randomization until the date of first documented progression
Chang in disease control rate (CR+PR+SD)
the end of every 2 treatment cycles(each cycle is 21 days), and every 3 months during follow-up until disease progression.The CR or PR patients were reconfirmed
Measured: Up to 24 weeks, From date of randomization until the date of first documented progression
Incidence of Treatment-Emergent Adverse Events (Safety and tolerability)
All adverse events were recorded regardless of their relevance to E10A
Measured: Up to 32 weeks, from date of randomization until the date of first documented progression or date
Overall survival
from cycle 2 to cycle 4 and calculated the survival during follow-up
Measured: Up to 24 month, through study completion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2015 (estimated)
- Study startJun 2013
- Primary completionJun 2016 (estimated)
- Study completionDec 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Head and Neck NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 540 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Guangzhou Double Bioproducts Co., Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Huiqiang Huang, Ph.D, Principal investigator, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02630264
- Sponsor's protocol ID
- E10AIII
- Status last verified
- Dec 2015
- First submitted
- 26 Dec 2013
- Last updated
- 15 Dec 2015
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Ye W, Liu R, Pan C, Jiang W, Zhang L, Guan Z, Wu J, Ying X, Li L, Li S, Tan W, Zeng M, Kang T, Liu Q, Thomas GR, Huang M, Deng W, Huang W. Multicenter randomized phase 2 clinical trial of a recombinant human endostatin adenovirus in patients with advanced head and neck carcinoma. Mol Ther. 2014 Jun;22(6):1221-1229. doi: 10.1038/mt.2014.53. Epub 2014 Mar 25.
PubMed 24662947Lin X, Huang H, Li S, Li H, Li Y, Cao Y, Zhang D, Xia Y, Guo Y, Huang W, Jiang W. A phase I clinical trial of an adenovirus-mediated endostatin gene (E10A) in patients with solid tumors. Cancer Biol Ther. 2007 May;6(5):648-53. doi: 10.4161/cbt.6.5.4004. Epub 2007 Feb 13.
PubMed 17426445
Study at a glance
From the registry record, last updated by the sponsor on 15 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Open-label, Multi-center Phase III Study Designed to Evaluate the Safety and Efficacy of E10A in Patients With Recurrent/Unresectable Squamous Cell Carcinoma of the Head and Neck Region
- ClinicalTrials.gov ID
- NCT02630264
- Acronym / sponsor ID
- E10AIII
- Conditions
- Head and Neck Neoplasms
- Keywords
- clinical trial, Recombinant Human Endostatin Adenovirus, randomized
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 540 participants (estimated)
- Lead sponsor
- Guangzhou Double Bioproducts Co., LtdIndustry (pharma, biotech, devices)
- Study start
- Jun 2013
- Primary completion
- Jun 2016 (estimated)
- Study completion
- Dec 2016 (estimated)
- First posted
- 15 Dec 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Recombinant human endostatin adenovirus injection is a novel anti-tumor gene therapy drug. E10A contains a recombinant human endostatin gene with the second-generation recombinant adenovirus as its vector. After transfection tumor cells. E10A expresses human endostatin, which inhibits vascular endothelial cell proliferation and tumor angiogenesis, and blocks tumor blood supply, thereby specifically inhibiting tumor growth and inducing apoposis of tumor cells. Both pre-clinical and animal models have demonstrated the anti-tumor activities of E10A. The safety and efficacy of E10A in treating head and neck cancer has also been demonstrated in Phase I and Phase II studies.
Detailed description
Phase II Clinical Study From March 2008 to December 2010 Safety and efficacy of intratumoral injections of E10A to cisplatin and paclitaxel was evaluated a multicenter, open-label, randomized clinical study in patients with advanced head and neck squamous cell carcinoma.
136 eligible patients were recruited and randomly assigned. Patients with locally advanced or metastatic head and neck squamous cell carcinoma or nasopharyngeal carcinoma not suitable for operation or radiotherapy were randomly assigned to receive E10A plus chemotherapy every 21 for a maximum of six cycles or to receive chemotherapy only.
The primary end point was the objective response rate (RR), defined as the proportion of patients who had a complete response (CR) or partial response (PR) at the target tumor lesion. The secondary end points were the objective disease control rate (DCR, or stable disease (SD) + PR + CR at the target tumor lesion), the overall RR, the overall DCR, OS, and progression-free survival (PFS).
The administration of E10A benefited some subgroups of patients. In the HNSCC patients, the objective RR was 36.5% (15/41) with E10A administration, exhibiting a trend of exceeding the rate of 20.0% (7/35) in the control group (P = 0.090; OR: 0.43), whereas the objective RR was 44.4% (12/27) versus 40.6% (13/32) in the NPC patients (P = 0.487; OR: 0.86). Patients who had previously received chemotherapy in the E10A group had a 44.8% (12/29) objective RR, whereas patients in the control group had only a 22.6% objective RR (7/31; P = 0.06, OR: 0.36). In contrast, patients without previous chemotherapy had a similar RR in both groups (34.3 versus 39.4%; P = 0.426, OR: 1.25).
The difference in the Kaplan-Meier estimates of PFS favored chemotherapy plus E10A, which resulted in a 3.43-month improvement. With a median follow-up of 10.47 months, the median PFS was 3.60 months (interquartile range: 2.60-7.63) in the control group and 7.03 months (interquartile range: 3.27-13.73) in the E10A group. As The median PFS was 3.60 months (interquartile range: 2.60-7.63) in the control group and 7.03months (interquartile range: 3.27-13.73) in the E10A group.
The OS of the E10A group was relatively prolonged in different subgroups compared with the controls (e.g., 13.37 months versus 9.67 months in the HNSCC patients, 13.03 months versus 10.50 months in those who had received prior treatment; Figure 1), but these results did not translate into significantly superior survival.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Combination therapy | Experimental | Drug: Endostatins, Drug: Paclitaxel injection, Drug: Cisplatin injectionE10A+chemotherapy group (360 subjects): 1. E10A (Endostatins) of 1.0×1012VP on day 1 and 6 2. Paclitaxel Injection 160mg/m2 on day 3 3. Cisplatin Injection 25mg/m2 on day 3, 4, and 5. Repeat every 21 days. |
| Chemotherapy | Experimental | Drug: Paclitaxel injection, Drug: Cisplatin injectionChemotherapy-alone group (180 subjects): 1. Paclitaxel Injection 160mg/m2 on day 1 2. Cisplatin Injection 25mg/m2 on day 1, 2, and 3. Repeat every 21 days |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients older than 18 years with histologically or cytologically proven locoregionally advanced or metastatic HNSCC (excluding NPC) not suitable for operation or radiotherapy
- A life expectancy≧12 weeks.
- Patients were required to have at least one measurable (by imaging or photograph complied RECIST) lesion with the largest diameter ≧2 cm and suitable for the intratumoral injection of E10A,
- Not received chemotherapy, radiotherapy, or biotherapy within 4 weeks.
- Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0-2.
Key exclusion criteria (8 listed)
- Known allergies to the study drug.
- The presence of important blood vessels/nerves or ulceration in the target lesion not suitable for injection.
- Tumor relapses within 6 months after paclitaxel chemotherapy.
- Severe coagulation disorders or bleeding tendency.
- Severe uncontrolled medical conditions.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EndostatinsAlso: E10ASpecification: 1mL/division, 1×1012 VP/1.0mL E10A preparation: 1. Thaw frozen E10A stored at -20°C vials at room temperature until E10A is liquid. 2. Swirl gently. Do NOT shake. Method of administration 1. E10A was diluted with 0.9% sodium chloride to appropriate dose according to the longest diameter of the target lesion. 2. After local anesthesia, we penetrated the syringe under normal skin subcutaneously 5 mm into the tumor or vertically into the lymph node under direct visualization and withdrew it to confirm the absence of blood. 3. Applied local compression for 10 minutes and pasted a sterile sticker on the injection site to avoid bleeding. | Drug | Combination therapy |
| Paclitaxel injectionSpecification: 30mg/5mL, Usage: 160mg/m2 on day 3, according to instruction. | Drug | Chemotherapy, Combination therapy |
| Cisplatin injectionSpecification: 20mg Usage: Cisplatin 25mg/ m2 on day 3, 4, and 5,according to instruction. | Drug | Chemotherapy, Combination therapy |
Primary outcome
Time to progression
Time frame: Up to 24 weeks
Time to progression is defined as the time from randomization until objective tumor progression as verified for the first time
4 secondary outcomes
Change in Overall response rate (CR+PR)
Time frame: Up to 24 weeks, from date of randomization until the date of first documented progression
Chang in disease control rate (CR+PR+SD)
Time frame: Up to 24 weeks, From date of randomization until the date of first documented progression
Incidence of Treatment-Emergent Adverse Events (Safety and tolerability)
Time frame: Up to 32 weeks, from date of randomization until the date of first documented progression or date
Overall survival
Time frame: Up to 24 month, through study completion
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Dec 2015.
- Results publication: PubMed 24662947Ye W, Liu R, Pan C, Jiang W, Zhang L, Guan Z, Wu J, Ying X, Li L, Li S, Tan W, Zeng M, Kang T, Liu Q, Thomas GR, Huang M, Deng W, Huang W. Multicenter randomized phase 2 clinical trial of a recombinant human endostatin adenovirus in patients with advanced head and neck carcinoma. Mol Ther. 2014 Jun;22(6):1221-1229. doi: 10.1038/mt.2014.53. Epub 2014 Mar 25.
- Results publication: PubMed 17426445Lin X, Huang H, Li S, Li H, Li Y, Cao Y, Zhang D, Xia Y, Guo Y, Huang W, Jiang W. A phase I clinical trial of an adenovirus-mediated endostatin gene (E10A) in patients with solid tumors. Cancer Biol Ther. 2007 May;6(5):648-53. doi: 10.4161/cbt.6.5.4004. Epub 2007 Feb 13.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Huiqiang Huang, Ph.D principal investigator
Sun Yat-sen University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Endostatins, Paclitaxel injection and Cisplatin injection in people with Head and Neck Neoplasms, run by Guangzhou Double Bioproducts Co., Ltd at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 15 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Huiqiang Huang, Ph.d ((86)2087343350, huanghq@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to progression (time frame: Up to 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02630264, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Dec 2015.