Clinical trial NCT05234905: H101 Combined With Camrelizumab for Recurrent Cervical Cancer
Official title: Oncolytic Virus(H101) Combined With Camrelizumab for Recurrent Cervical Cancer: a Prospective, Multicenter Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Uterine Cervical Neoplasms
Oncolytic Virotherapy
Camrelizumab
Keywords: Recurrent cervical cancer
H101
Camrelizumab
Objective response rate
Lead sponsor: Zhejiang Cancer Hospital
Sponsor class: OTHER
First posted: 2022-02-10
Enrollment: 55
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: There is no standard treatment for recurrent cervical cancer that progresses or persists after first-line treatment. The objective response rate of anti-PD-1 antibody treatment is about 15%. The purpose of this study was to evaluate whether the regimen could improve the objective response rate by intratumoral injection of oncolytic virus(recombinant human adenovirus type 5 injection, H101) combined with anti-PD-1 antibody(camrelizumab).

Detailed description: 1. Main research purpose To evaluate the efficacy of H101 combined with camrelizumab in patients with incurable recurrent cervical cancer.
2. Secondary research purpose To evaluate other curative effects of H101 combined with camrelizumab in patients with incurable recurrent cervical cancer.

   To evaluate the safety of H101 combined with camrelizumab in patients with incurable recurrent cervical cancer.
3. Purpose of Exploratory Research To explore the changes of tumor microenvironment before and after H101 injection and the mechanism of action in combination with PD-1, and to accurately screen the beneficiaries based on molecular expression.
4. Overall experimental design This study is a multicenter, prospective, clinical study to investigate the efficacy and safety of H101 combined with camrelizumab in the treatment of incurable recurrent cervical cancer patients. It is expected that 55 subjects will be enrolled.

   The study was divided into 5 phases: screening period, baseline period, treatment period, and follow-up period. Patients with recurrent cervical cancer who were eligible for inclusion and were incurable by previous first-line treatment were screened. During the follow-up period, follow-up was conducted every 1 month for at least 2 years.
5. Subject population The target population of this study was patients with recurrent cervical squamous cell carcinoma/adenocarcinoma/adenosquamous carcinoma who were incurable after first-line therapy.
6. Treatment allocation All subjects enrolled in this study received H101 combined with camrelizumab.
7. Drug dosage and administration in the trial Dosing regimen: H101 + camrelizumab. 1) H101: 1 lesion was selected for intratumoral injection. Intratumoral injection of H101 was used on the 1st and 4th day of each cycle, repeated once in 3 weeks. H101 dosage: Tumor maximum diameter ≤5 cm, 1.5×10\^12vp (3 injections) on day 1 and 1.0×10\^12vp (2 injections) on day 4.

Tumor maximum diameter \>5cm but ≤10cm, 3.0×10\^12vp (6 injections) on day 1, 2.0×10\^12vp (4 injections) on day 4.

Tumor maximum diameter \>10cm, 4.5×10\^12vp (9 injections) on day 1 and 3.0×10\^12vp (6 injections) on day 4.

H101 will be used until injected lesion disappears or 5 cycles, whichever occurs first.

2) Camrelizumab: 200 mg intravenously. Dosing after H101 on day 1 of each cycle, repeated 3 weeks. The drug was discontinued or discontinued for 2 years until the patient developed tumor progression or intolerable toxicity.

Eligibility criteria: Inclusion Criteria:

All of the following criteria must be met for inclusion:

1. Participants voluntarily participated in this study and signed the informed consent;
2. 18-80 years old;
3. Cervical squamous cell carcinoma/adenocarcinoma/adenosquamous carcinoma;
4. Participants with incurable recurrence after first-line treatment or participants with incurable recurrence within the irradiation field;
5. At least one lesion that meets RICIST 1.1 criteria can be evaluated and can be injected intratumorally;
6. ECOG score 0-2 points;
7. Expected survival \> 3 months;
8. Women of childbearing age must undergo a pregnancy test (serum or urine) before enrollment, and the result is negative, and they are willing to use appropriate methods of contraception during the trial;
9. Those who can tolerate and comply with the trial protocol, as determined by the investigator.

Exclusion Criteria:

Those who have one of the following conditions should be excluded and cannot be selected:

1. There is an infection at the intended injection site;
2. Liver cirrhosis, decompensated liver disease;
3. Have a history of immunodeficiency, including HIV positive or other acquired congenital immunodeficiency diseases;
4. Chronic renal insufficiency and renal failure;
5. Combined with other malignant tumor patients who still need treatment and/or newly diagnosed within 5 years;
6. Myocardial infarction, severe arrhythmia and ≥ grade 2 congestive heart failure (New York Heart Association (NYHA) classification);
7. Complications, need to take drugs with serious liver and kidney damage during treatment, such as tuberculosis;
8. Previous use of anti-PD-1 drugs or oncolytic viruses;
9. Patients who cannot understand the experimental content and cannot cooperate and those who refuse to sign the informed consent;
10. Those with concomitant diseases or other special conditions that seriously endanger the safety of patients or affect the completion of the study.

Primary outcomes:
measure: ORR(Objective Response Rate)
timeFrame: 2 years
Secondary outcomes:
measure: PFS(Progression Free Survival)
timeFrame: 2 years
measure: DCR(Disease Control Rate)
timeFrame: 2 years
measure: OS(Overall Survival)
timeFrame: 2 years
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
city: Jinhua
country: China
facility: Jinhua Municipal Central Hospital Medical Group
city: Ningbo
country: China
facility: Ningbo First Hospital
city: Taizhou
country: China
facility: Taizhou Central Hospiatl
Study officials:
affiliation: Zhejiang Cancer Hospital
name: Xiang Zhang
role: STUDY_DIRECTOR
References: