Recurrent or Metastatic Cervical Cancer
Conditions
Brief summary
This is a randomized, open-label, 3-arm Phase 2 study to evaluate the efficacy and safety of SHR-1210 alone or with SHR-1020 versus physician's choice chemotherapy in recurrent or metastatic cervical cancer patients. All enrolled patients will be randomly divided into 3 groups and receive treatment until disease progression, intolerable toxicity，any criterion for stopping the study drug or SHR-1210 treatment for up to 2 years.
Detailed description
This is a randomized, open-label, 3-arm Phase 2 study to evaluate the efficacy and safety of SHR-1210 alone or with SHR-1020 versus physician's choice chemotherapy in recurrent or metastatic cervical cancer patients. All enrolled patients will be randomly divided into 3 groups and receive treatment until disease progression, intolerable toxicity，any criterion for stopping the study drug or SHR-1210 treatment for up to 2 years.The primary study hypotheses are that the combination of SHR-1210 plus SHR-1020 is superior to SHR-1210 or physician's choice chemotherapy with respect to: 1) Progression free survival(PFS) in recurrent or metastatic cervical cancer patients(SHR-1210+SHR-1020 versus SHR-1210；2) Overall survival(OS) in recurrent or metastatic cervical cancer patients(SHR-1210+SHR-1020 versus Physician's choice chemotherapy).
Interventions
DRUGSHR-1210
SHR-1210 intravenously every 3 weeks
DRUGSHR-1020
SHR-1020 Orally once daily
Investigators will declare one of the following regimens:Albumin-bound paclitaxel injection, Pemetrexed disodium for injection, Gemcitabine for injection
Sponsors
Jiangsu HengRui Medicine Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Voluntarily agree to participate by giving written informed consent. 2. Histologically or cytologically confirmed diagnosis of squamous-cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix. 3. The patients relapsed after a platinum-based treatment regimen for recurrent or metastatic disease. 4. Patients must provide a fresh biopsy. If not, sufficient and adequate tumor tissue sample from the most recent biopsy of a tumor lesion will be required for PD-L1 expression. 5. Has measurable lesion on imaging based on RECIST version 1.1. 6. Have a life expectancy of at least 3 months. 7. ECOG performance status 0-1. 8. If childbearing potential, female patients must be willing to use at least 1 adequate barrier methods throughout the study, starting with the screening visit through 6 months after the last dose of study treatment.
Exclusion criteria
1. Has any malignancy \<5 years prior to study entry. Except for curative skin basal cell carcinoma, carcinoma in situ or breast cancer \>3 years. 2. Has received prior therapy with: anti-PD-1, anti-PD-L1, or anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibodies; Famitinib; patient is allergic to monoclonal antibody. 3. Known to have autoimmune disease. 4. Recived other anticancer therapy 4 weeks before randomization. 5. Known to be human immunodeficiency virus positive, active hepatitis B virus, or active hepatitis C virus. 6. Untreated and/or uncontrolled brain metastases. 7. With high risk of vaginal bleeding or gastrointestinal perforation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) assessed by Blinded Independent Central Review in recurrent or metastatic cervical cancer patients(SHR-1210+Famitinib versus SHR-1210) | Up to approximately 2 years | Defined as the number of subjects with a best overall response (BOR) of CR (Disappearance of all target lesions) or PR (At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) divided by the number of measurable subjects with target lesion at baseline according to RECIST 1.1 criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) in recurrent or metastatic cervical cancer patients(SHR-1210+Famitinib versus SHR-1210) | Up to approximately 2 years | OS is the time interval from randomization to death due to any reason or lost of follow-up. |
| Objective Response Rate (ORR) assessed by investigator in recurrent or metastatic cervical cancer patients(SHR-1210+Famitinib versus SHR-1210) | Up to approximately 2 years | Defined as the number of subjects with a best overall response (BOR) of CR (Disappearance of all target lesions) or PR (At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) divided by the number of measurable subjects with target lesion at baseline according to RECIST 1.1 criteria. |
| Disease control rate (DCR)，recurrent or metastatic cervical cancer patients(SHR-1210+Famitinib versus SHR-1210) according to RECIST 1.1 criteria | Up to approximately 2 years | Defined as the number of subjects with a best overall response (BOR) of CR (Disappearance of all target lesions), PR (At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) or SD (Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.) divided by the number of measurable subjects with target lesion at baseline according to RECIST 1.1 criteria. |
| Duration of response (DoR), in recurrent or metastatic cervical cancer patients(SHR-1210+Famitinib versus SHR-1210) according to RECIST 1.1 criteria. | Up to approximately 2 years | For participants who demonstrate CR or PR, DOR is defined as the time from first documented evidence of CR or PR until disease progression or death from any cause, whichever came first. The DOR per RECIST 1.1 as assessed by Investigator will be presented. |
| Time to response (TTR), in recurrent or metastatic cervical cancer patients(SHR-1210+Famitinib versus SHR-1210) according to RECIST 1.1 criteria. | Up to approximately 2 years | Defined as the time from randomization to the first objective tumor response (At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters)) observed for patients who achieved a CR or PR. |
| Time to treatment failure (TTF)，in recurrent or metastatic cervical cancer patients(SHR-1210+Famitinib versus SHR-1210) according to RECIST 1.1 criteria. | Up to approximately 2 years | Defined as the time from randomization to the end of treatment or death from any cause, whichever came first. |
| Progression free survival (PFS) in recurrent or metastatic cervical cancer patients(SHR-1210+Famitinib versus SHR-1210) | Up to approximately 2 years | PFS is defined as from the time of randomization until the date of first documented progression or date of death from any cause, whichever came first. |
| Tolerance | from the first drug administration to within 90 days for the last treatment dose | To calculate the proportion of dose interruption, dose reduction or dose termination because of drug-related toxicity |
| Characteristic of Anti drug antibody | from the first drug administration to within 90 days for the last treatment dose | Defined as ratio of ADAs of SHR-1210 during the treatment compared to baseline. |
| Peak Serum Concentration of SHR-1210 | from the first drug administration to within 90 days for the last treatment dose | Defined as peak serum concentration of SHR-1210 during the treatment compared to baseline |
| Peak Plasma Concentration of famitinib | from the first drug administration to within 90 days for the last treatment dose | Defined as peak plasma concentration of famitinib during the treatment compared to baseline |
| Area under the Serum Concentration versus Time Curve of SHR-1210 | from the first drug administration to within 90 days for the last treatment dose | Defined as area under the serum concentration versus time curve of SHR-1210 during the treatment compared to baseline |
| Area under the Plasma Concentration versus Time Curve of famitinib | from the first drug administration to within 90 days for the last treatment dose | Defined as area under the plasma concentration versus time curve of famitinib during the treatment compared to baseline |
| Adverse Events (AEs) | from the first drug administration to within 90 days for the last treatment dose | — |
Countries
China
Outcome results
None listed