SHR-1210 in Combination With Apatinib in Patients With Metastatic, Persistent, or Recurrent Cervical Cancer

NCT03816553 | Completed Phase 2 DMC

• 1 other identifier: B2018-169-01
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to explore the efficacy and safety of SHR-1210 in combination with apatinib in treating patients with metastatic, persistent, or recurrent cervical cancer.

Conditions

Recurrent Cervical Carcinoma; Metastatic Cervical Cancer

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  ORR is defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

  Up to approximately 12 months

Secondary Outcomes (7)

• Progression-free Survival (PFS)

  Up to approximately 24 months

• Overall survival (OS)

  Up to approximately 24 months

• 6-month PFS rate

  From date of enrollment up to 6 months

• 9-month OS rate

  From date of enrollment up to 9 months

• Duration of Response (DCR)

  Up to approximately 24 months

Other Outcomes (4)

• Impact of the treatment on Quality of Life (QOL) measured by the Functional Assessment of Cancer Therapy (FACT)-Cervical Trial Outcome of Index (FACT-Cx TOI)

  Baseline, every other cycle (each cycle is 28 days) and up to approximately 24 months

• Pain assessed by Brief Pain Inventory (BPI)

  Baseline, every other cycle (each cycle is 28 days) and up to approximately 24 months

• PD-L1 expression on tumor and immune cells

  Up to approximately 24 months

Study Arms (1)

SHR-1210 + Apatinib

EXPERIMENTAL

Participants receive SHR-1210 200mg (3mg/kg for underweight patients) intravenously every 2 weeks and apatinib 250mg orally once daily until disease progression or unacceptable toxicity

Drug: SHR-1210; Drug: Apatinib

Interventions

SHR-1210 DRUG

SHR-1210 will be administered as a 30-minute IV infusion Q2W at a dose of 200mg (3mg/kg for underweight patients).

Also known as: Camrelizumab

SHR-1210 + Apatinib

Apatinib DRUG

Apatinib will be administered 250mg orally, once daily until progression.

Also known as: Apatinib Mesylate

SHR-1210 + Apatinib

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have metastatic, recurrent or persistent squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix which is not amenable to curative treatment with surgery and/or radiation therapy;
• Age ≥ 18 years and ≤ 70 years;
• Patients must have measurable disease per RECIST 1.1; measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded as ≥ 10 mm with computed tomography (CT) scan, magnetic resonance imaging (MRI),; a lymph node must be ≥ 15 mm in short axis. Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Life expectancy exceeds 3 months;
• Patients must have had at least one prior systemic chemotherapeutic regimen for management of recurrent, persistent or metastatic carcinoma of the cervix.
• Note: Prior adjuvant therapy is NOT counted as a systemic chemotherapeutic regimen for management of recurrent, persistent or metastatic carcinoma of the cervix; adjuvant therapy includes cisplatin given concurrent with primary radiation therapy (CCRT) and adjuvant chemotherapy given following the completion of concurrent chemotherapy and radiation therapy
• Patients must have adequate organ function
• Absolute neutrophil count (ANC) ≥ 1.5×10\^9/L
• Platelet count ≥ 80 × 10\^9/L
• Hemoglobin ≥ 90 g/L
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 × ULN (however, patients with known liver metastasis who have AST or ALT level ≤ 5 × ULN may be enrolled)
• Creatinine ≤ 1.5 × ULN or creatinine clearance rate ≥ 60 ml/min (Cockcroft-Gault formula)
• Baseline albumin ≥ 28 g/L

You may not qualify if:

• Histopathologic diagnoses of tumors other than squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma.
• Participated in other clinical trials, or finish other clinical trials within 4 weeks.
• Prior exposure to immune checkpoint inhibitors, including but not limited to other anti-PD-1 and anti-PD-L1 antibodies, or prior exposure to apatinib.
• Known history of hypersensitivity to any components of the SHR-1210 formulation, or other monoclonal antibody.
• Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids. Doses \> 10 mg/day prednisone or equivalent are prohibited within 2 weeks before study drug administration.
• Patients with any active autoimmune disease or history of autoimmune disease, including but not limited to the following: hepatitis, pneumonitis, uveitis, colitis (inflammatory bowel disease), hypophysitis, vasculitis, nephritis, hyperthyroidism, and hypothyroidism, except for subjects with vitiligo or resolved childhood asthma/atopy. Asthma that requires intermittent use of bronchodilators or other medical intervention should also be excluded.
• Clinically significant cardiovascular diseases, including but not limited to congestive heart failure (New York heart association (NYHA) class \> 2), unstable or severe angina, severe acute myocardial infarction within 1 year before enrollment, supraventricular or ventricular arrhythmia which need medical intervention, or QT interval male ≥ 450 ms, female ≥ 470 ms.
• Arterial thrombus or phlebothrombosis within 6 months.
• Hypertension that can not be well controlled through antihypertensive drugs (systolic pressure ≥ 140 mm Hg and/or diastolic pressure ≥ 90 mm Hg)
• Proteinuria ≥ (++) or 24 hours total urine protein \> 1.0 g.
• Coagulation abnormalities (INR\>2.0、PT\>16s), with bleeding tendency or are receiving thrombolytic or anticoagulant therapy.
• Has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events (except for alopecia) due to a previously administered agent.
• Has known active central nervous system metastases.
• Patients with a prior invasive malignancy who have had any evidence of disease within the last 5 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
• Has an active infection requiring systemic therapy.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (3)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

Guangzhou Panyu Central Hospital

Guangzhou, Guangdong, 511400, China

Location

The First affiliated Hospital of Sun Yat-sen University

Guanzhou, Guangdong, 510080, China

Location

Related Publications (3)

• Wang Y, Lai Y, Peng H, Yan S, Liu Z, Tong C, Huang X. Multiparametric immune profiling of advanced cervical cancer to predict response to programmed death-1 inhibitor combination therapy: an exploratory study of the CLAP trial. Clin Transl Oncol. 2023 Jan;25(1):256-268. doi: 10.1007/s12094-022-02945-1. Epub 2022 Sep 17.

  PMID: 36115931 DERIVED

• Huang X, He M, Peng H, Tong C, Liu Z, Zhang X, Shao Y, Zhu D, Zhang J, Yin JC, Yang F, Lan C. Genomic profiling of advanced cervical cancer to predict response to programmed death-1 inhibitor combination therapy: a secondary analysis of the CLAP trial. J Immunother Cancer. 2021 May;9(5):e002223. doi: 10.1136/jitc-2020-002223.

  PMID: 34011535 DERIVED

• Lan C, Shen J, Wang Y, Li J, Liu Z, He M, Cao X, Ling J, Huang J, Zheng M, Zou G, Yan H, Liu Q, Yang F, Wei W, Deng Y, Xiong Y, Huang X. Camrelizumab Plus Apatinib in Patients With Advanced Cervical Cancer (CLAP): A Multicenter, Open-Label, Single-Arm, Phase II Trial. J Clin Oncol. 2020 Dec 1;38(34):4095-4106. doi: 10.1200/JCO.20.01920. Epub 2020 Oct 14.

  PMID: 33052760 DERIVED

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

camrelizumab; apatinib

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 13, 2019
• First Posted: January 25, 2019
• Study Start: January 19, 2019
• Primary Completion: April 30, 2020
• Study Completion: August 31, 2022
• Last Updated: April 11, 2023

Record last verified: 2023-04

Locations

CN (3)