Intra-tumor Injection of Oncolytic Viruses H101 Combined With or Without Radiotherapy in Refractory/Recurrent Gynecological Malignancies

Study Overview
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Brief Summary
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The purpose of this clinical trial is to evaluate the effectiveness and safety of oncolytic viruses H101 intra-tumor injection combined with or without radiotherapy in refractory or recurrent gynecological malignancies. And further research the mechanism of oncolytic viruses H101.

Detailed Description
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Patients with recurrent, radiation/chemotherapy-resistant gynecological cancer carry a poor prognosis. H101 is a recombinant human type-5 adenovirus (Ad5), in which the E1B and E3 gene have been deleted. Previous studies have shown that H101 has anticancer activity and safety in some solid tumors, but has little report in gynecological oncology. In this clinical trial, 60 recurrent or refractory gynecological cancer patients will be enrolled. Based on individual conditions, all eligible patients are intra-tumor injected oncolytic viruses H101 within 5 consecutive days combined with or without radiotherapy in sequential, three weeks for a cycle (1-4 cycles totally). Simultaneously, the tumor sample, peripheral blood, and urine specimen were collected on day1 and day5. Local control rate and side effects are recorded respectively.

Official Title
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Intra-tumor Injection of Oncolytic Viruses H101 Combined With or Without Radiotherapy in Refractory/Recurrent Gynecological Malignancies

Conditions
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Genital Neoplasms, Female

Intervention / Treatment
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* Drug: H101


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent obtained. Age ≥ 18 years at the time of study entry. Histological or Cytologically diagnosed gynecological malignancies. Failure to prior standard treatment (surgery, chemotherapy, radiotherapy); Refractory/recurrence/metastasis gynecological cancer At least one measurable lesion according to the RECIST1.1. Cooperative Oncology Group-Status (ECOG Status) 0-3. The last treatment should be over 2 weeks. Exclusion Criteria: History or evidence of active autoimmune disease that requires systemic treatment. Participated in other anti-tumor clinical trials within 4 weeks. Patients who have a contraindication to similar drugs. That failure to follow up regularly.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oncorine (H101) with or without radiotherapy<br>The tumor mass was injected with H101 per day for 5 consecutive days, 3 weeks as one treatment cycle, and 1 to 4 cycles according to the condition of the patient, and the patient was treated with or without radiotherapy in sequential. The injection dose of H101 was determined by the tumor volume or maximum tumor diameter:5.0×10^11 virus particles(VP) for if tumor diameter≤5cm; 1×10^12 VP for the tumor diameter between 5cm and 10cm, and 1.5×10^12 VP for the tumor diameter>10cm. | Drug: H101<br>* Intra-tumor injected oncolytic viruses H101 within 5 consecutive days,3 weeks for a cycle (1-4cycles)<br>* Other names: Radiotherapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local Control (LC) | LC will be measured from the start date of injection until the date of progressive disease | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | ORR is the percentage of participants with presence of complete response (CR), partial response (PR). ORR assessment will be based on RECIST 1.1 criteria | 1 year after injection | 
| Progress free survival (PFS) | Progress free survival is defined as the time from first day of injection until the first date of either objective disease progression or death due to any cause | 12 months | 
| adverse events | Toxicity were graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 | At day 3, 7 and 30 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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H101, Cervical Cancer, Ovary Cancer, Endometrial Cancer, Vaginal Neoplasms, Vulvar Neoplasms