SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT02630264

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

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.

NCT02630264 Head and Neck Neoplasms
MeSH: Carcinoma, Squamous Cell Squamous Cell Carcinoma of Head and Neck Head and Neck Neoplasms
HPO: Neoplasm of head and neck Squamous cell carcinoma

3 Interventions

Name: Endostatins

Description: 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.

Type: Drug

Combination therapy

Name: Paclitaxel injection

Description: Specification: 30mg/5mL, Usage: 160mg/m2 on day 3, according to instruction.

Type: Drug

Combination therapy Chemotherapy

Name: Cisplatin injection

Description: Specification: 20mg Usage: Cisplatin 25mg/ m2 on day 3, 4, and 5,according to instruction.

Type: Drug

Combination therapy Chemotherapy


Primary Outcomes

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

Measure: Time to progression

Time: Up to 24 weeks

Secondary Outcomes

Description: 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.

Measure: Change in Overall response rate (CR+PR)

Time: Up to 24 weeks, from date of randomization until the date of first documented progression

Description: 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

Measure: Chang in disease control rate (CR+PR+SD)

Time: Up to 24 weeks, From date of randomization until the date of first documented progression

Description: All adverse events were recorded regardless of their relevance to E10A

Measure: Incidence of Treatment-Emergent Adverse Events (Safety and tolerability)

Time: Up to 32 weeks, from date of randomization until the date of first documented progression or date

Description: from cycle 2 to cycle 4 and calculated the survival during follow-up

Measure: Overall survival

Time: Up to 24 month, through study completion

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There is one SNP

SNPs


1 E10A

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. --- E10A ---

E10A for the Treatment of Squamous Cell Carcinoma of the Head and Neck Recombinant human endostatin adenovirus injection is a novel anti-tumor gene therapy drug. --- E10A ---

E10A contains a recombinant human endostatin gene with the second-generation recombinant adenovirus as its vector. --- E10A ---

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. --- E10A ---

Both pre-clinical and animal models have demonstrated the anti-tumor activities of E10A. --- E10A ---

The safety and efficacy of E10A in treating head and neck cancer has also been demonstrated in Phase I and Phase II studies. --- E10A ---

All adverse events were recorded regardless of their relevance to E10A. --- E10A ---

3. 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, 4. --- E10A ---

Recent history of myocardial infarction acute infection, pregnancy or lactation, or symptomatic brain metastases 7. A history of corticosteroids or immunosuppressives use within four weeks of study entry 8. Received any chemotherapy or radiotherapy within four weeks of study entry Head and Neck Neoplasms Carcinoma, Squamous Cell Squamous Cell Carcinoma of Head and Neck Head and Neck Neoplasms 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. --- E10A ---

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. --- E10A ---

The administration of E10A benefited some subgroups of patients. --- E10A ---

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). --- E10A ---

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). --- E10A ---

The difference in the Kaplan-Meier estimates of PFS favored chemotherapy plus E10A, which resulted in a 3.43-month improvement. --- E10A ---

in the E10A group. --- E10A ---

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. --- E10A ---



HPO Nodes


HPO:
Neoplasm of head and neck
Genes 21
ASCC1 FOXE1 MSR1 RNF6 RHBDF2 APC PDGFRA CTHRC1 KIT TGFBR2 STK11 HABP2 DLEC1 STAT1 SDHA SDHB SDHC MINPP1 WWOX RAD21 FH
Squamous cell carcinoma
Genes 62
BLM TYR CDKN2A NUTM1 TGFBR2 KRT5 COL7A1 GTF2E2 GJB2 ERCC2 KRT14 ERCC3 CIB1 ERCC4 ERCC5 WWOX LMNA SASH1 RNF6 TINF2 ING1 SLC17A9 DOCK8 LZTS1 PSENEN FDPS NTHL1 CTSC GJB6 BRD4 POLH RECQL4 RNF113A TMC6 FERMT1 MC1R WRN TMC8 LAMA3 MPLKIP GTF2H5 WNT10A DKC1 LAMB3 NLRP1 LAMC2 SLC45A2 OCA2 XPC MMP1 TNFRSF10B DCC WRAP53 TERC TERT RSPO1 DDB2 SLX4 STAT1 MVD IL7 MVK