A Study of SHR-1210± SHR-1020 Versus Chemotherapy in Patients With Recurrent or Metastatic Cervical Cancer
- Conditions
- Recurrent or Metastatic Cervical Cancer
- Interventions
- Registration Number
- NCT04680988
- Lead Sponsor
- Jiangsu HengRui Medicine Co., Ltd.
- 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).
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Female
- Target Recruitment
- 194
- Voluntarily agree to participate by giving written informed consent.
- Histologically or cytologically confirmed diagnosis of squamous-cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix.
- The patients relapsed after a platinum-based treatment regimen for recurrent or metastatic disease.
- 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.
- Has measurable lesion on imaging based on RECIST version 1.1.
- Have a life expectancy of at least 3 months.
- ECOG performance status 0-1.
- 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.
- Has any malignancy <5 years prior to study entry. Except for curative skin basal cell carcinoma, carcinoma in situ or breast cancer >3 years.
- 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.
- Known to have autoimmune disease.
- Recived other anticancer therapy 4 weeks before randomization.
- Known to be human immunodeficiency virus positive, active hepatitis B virus, or active hepatitis C virus.
- Untreated and/or uncontrolled brain metastases.
- With high risk of vaginal bleeding or gastrointestinal perforation.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Doublet Arm SHR-1020 SHR-1210+SHR-1020 Doublet Arm SHR-1210 SHR-1210+SHR-1020 Physician's choice chemotherapy Physician's choice chemotherapy Albumin-bound paclitaxel injection or Pemetrexed disodium for injection or Gemcitabine for injection Single Arm SHR-1210 SHR-1210
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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.
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.
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
Adverse Events (AEs) from the first drug administration to within 90 days for the last treatment dose 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
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.
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.
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.
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
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
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.
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
Trial Locations
- Locations (1)
Fudan University Shanghai Cancer Center
🇨🇳Shanghai, Shanghai, China