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Cervical cancer is the second-most common cancer in the world and is a leading cause of cancer death among women in developing countries. Cisplatin-based chemotherapy +/- bevacizumab have been recommended as the first-line treatment for patients who present with metastatic (e.g. stage IVB), persistent, or recurrent cervical cancer. However, patients in this setting are rarely curable. The immune checkpoint inhibitor (ICI) therapy, including cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed death-1 (PD-1), and programmed death-ligand 1 (PD-L1) inhibitors, has revolutionized the treatment of several cancers. The investigator previously reported the promising antitumor efficacy of camrelizumab (PD-1 inhibitor) combined with apatinib (VEGFR2 inhibitor) as second-line, or later, therapy in patients with advanced cervical cancer. This randomized study is to assess the efficacy and safety of first-line treatment with camrelizumab plus apatinib compared to the efficacy and safety of paclitaxel and cisplatin/carboplatin plus bevacizumab in patients with stage IVB, recurrent, or persistent cervical cancer.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Camrelizumab + Apatinib | Experimental | On Day 1 and Day 15 of each 28-day cycle, participants receive an intravenous (IV) infusion of camrelizumab 200 mg Plus an oral apatinib 250 mg once daily. Apatinib will be administered 250 mg once every other day when completing twice tumor assessement. All treatments are administered until disease progression or unacceptable toxicity. |
|
| Paclitaxel + Cisplatin/Carboplatin + Bevacizumab | Active Comparator | On Day 1 of each 21-day cycle, participants receive an intravenous (IV) infusion of paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH bevacizumab 15 mg/kg OR paclitaxel 175 mg/m^2 PLUS carboplatin Area Under the Curve (AUC) 5, WITH bevacizumab 15 mg/kg). All treatments are administered until disease progression or unacceptable toxicity. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Camrelizumab | Drug | IV injection |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Progression-Free Survival (PFS) | PFS defined as the time from randomization to the first documented disease progression per RECIST v1.1, or death due to any cause, whichever occurs first. | up to 36 months |
| Measure | Description | Time Frame |
|---|---|---|
| Objective Response Rate (ORR) | ORR is defined as the percentage of participants in the analysis population who have a complete response or a partial response per RECIST 1.1. | up to 24 months |
| Duration of Response (DOR) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Chunyan Lan, MD&PhD | Contact | +862087343870 | lanchy@sysucc.org.cn | |
| Yanmei Zhou | Contact | +8615521422771 | zhouyanmei@clincell.com |
| Name | Affiliation | Role |
|---|---|---|
| Xin Huang, MD | Sun Yat-Sen University Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sun Yat-sen University Cancer Center | Recruiting | Guangzhou | Guangdong | 510060 | China |
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| Apatinib | Drug | Oral |
|
| Paclitaxel | Drug | IV injection |
|
| Cisplatin | Drug | IV infusion |
|
| Carboplatin | Drug | IV infusion |
|
| Bevacizumab | Drug | IV infusion |
|
DOR is defined as the time from first documented evidence of CR or PR until disease progression per RECIST 1.1 or death due to any cause, whichever occurs first.
| up to 24 months |
| Disease Control Rate (DCR) | DCR is defined as the percentage of patients who have CR, PR, and stable disease (SD). | up to 24 months |
| Overall Survival (OS) | OS is defined as the time from the treatment to death due to any cause. | up to 48 months |
| Number of Subjects with treatment-related adverse events (AEs) | Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v5.0. | up to 48 months |
| Patient-reported outcomes (PROs) | PROs assessed by the Functional Assessment of Cancer Therapy-Cervix (FACT-Cx) Trial Outcome Index (TOI). The Functional Assessment of Cancer Therapy-General (FACT-G) is a 27-item self-report quality of life (QOL) measure that includes 4 subscales (physical well-being, social well-being, functional well-being and emotional well-being). The Trial Outcome of Index of FACT-Cx (FACT-Cx TOI) consists of two subscales from the FACT-G: Physical Well Being (7 items) and Functional Well Being (7 items), plus the Cervix Cancer-specific subscale (15 items). The total score is ranged 0-116 for FACT-Cx TOI. A higher score indicates better HRQL. | up to 48 months |
| ID | Term |
|---|---|
| D002583 | Uterine Cervical Neoplasms |
| ID | Term |
|---|---|
| D014594 | Uterine Neoplasms |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D002577 | Uterine Cervical Diseases |
| D014591 | Uterine Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D000091662 | Genital Diseases |
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| ID | Term |
|---|---|
| C000631724 | camrelizumab |
| C553458 | apatinib |
| D017239 | Paclitaxel |
| D002945 | Cisplatin |
| D016190 | Carboplatin |
| D000068258 | Bevacizumab |
| ID | Term |
|---|---|
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017672 | Nitrogen Compounds |
| D017671 | Platinum Compounds |
| D056831 | Coordination Complexes |
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
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