Sintilimab (PD-1 Antibody) and Chemoradiotherapy in Locoregionally-advanced Nasopharyngeal Carcinoma (CONTINUUM)
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ClinicalTrials.gov Identifier: NCT03700476 |
Recruitment Status :
Active, not recruiting
First Posted : October 9, 2018
Last Update Posted : March 28, 2023
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Condition or disease | Intervention/treatment | Phase |
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Nasopharyngeal Neoplasms | Drug: Sintilimab Drug: Gemcitabine Drug: Cisplatin Radiation: intensity-modulated radiotherapy | Phase 3 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 425 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Sintilimab (PD-1 Antibody) and Chemoradiotherapy in Locoregionally-advanced Nasopharyngeal Carcinoma: a Randomized, Multicenter, Phase 3 Trial |
Actual Study Start Date : | December 21, 2018 |
Actual Primary Completion Date : | February 28, 2023 |
Estimated Study Completion Date : | January 2025 |
Arm | Intervention/treatment |
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Experimental: Sintilimab arm
Patients will receive induction chemotherapy with gemcitabine (1g/m2, d1 & 8 of every cycle) and cisplatin (80mg/m2, d1 of every cycle), every 3 weeks for 3 cycles before radiation. Definitive intensity-modulated radiotherapy (IMRT) of 6996cGy in 33 fractions will be given. Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT. Sintilimab 200mg will be given every 3 weeks for 12 cycles, started on day 1 of induction chemotherapy.
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Drug: Sintilimab
Sintilimab 200mg will be given every 3 weeks for 12 cycles, started on day 1 of induction chemotherapy.
Other Names:
Drug: Gemcitabine Gemcitabine 1g/m2, d1 & 8 of every cycle, every 3 weeks for 3 cycles before radiation. Drug: Cisplatin Induction cisplatin 80mg/m2, every 3 weeks for 3 cycles before radiation; Concurrent cisplatin 100mg/m2, every 3 weeks for 2 cycles during radiation
Other Name: DDP Radiation: intensity-modulated radiotherapy Definitive intensity-modulated radiotherapy (IMRT) of 6996cGy will be given in 33 fractions.
Other Name: IMRT |
Active Comparator: Chemoradiation arm
Patients will receive induction chemotherapy with gemcitabine (1g/m2, d1 & 8 of every cycle) and cisplatin (80mg/m2, d1 of every cycle), every 3 weeks for 3 cycles before radiation. Definitive intensity-modulated radiotherapy (IMRT) of 6996cGy in 33 fractions will be given. Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT.
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Drug: Gemcitabine
Gemcitabine 1g/m2, d1 & 8 of every cycle, every 3 weeks for 3 cycles before radiation. Drug: Cisplatin Induction cisplatin 80mg/m2, every 3 weeks for 3 cycles before radiation; Concurrent cisplatin 100mg/m2, every 3 weeks for 2 cycles during radiation
Other Name: DDP Radiation: intensity-modulated radiotherapy Definitive intensity-modulated radiotherapy (IMRT) of 6996cGy will be given in 33 fractions.
Other Name: IMRT |
- Event-free survival (EFS) [ Time Frame: 3 years ]calculated from randomization to the date of locoregional recurrence, distant metastasis, or death from any cause, whichever occurred first.
- Overall survival (OS) [ Time Frame: 3 years ]calculated from randomization to the date of death from any cause.
- Distant metastasis-free survival (DMFS) [ Time Frame: 3 years ]calculated from randomization to the date of first distant metastasis, or death from any cause, whichever occurred first.
- Locoregional recurrence-free survival (LRFS) [ Time Frame: 3 years ]calculated from randomization to the date of locoregional persistence, 1st locoregional recurrence, or death from any cause, whichever occurred first.
- Adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: 3 years ]Graded according to CTCAE V5.0.
- Quality of life (QoL) [ Time Frame: 3 years ]The change of QoL from randomization to the start of radiotherapy, the end of radiotherapy, 34 weeks (at the end of sintilimab treatment in the sintilimab arm and the corresponding timepoint in the chemoradiation arm), 2 years and 3 years after randomization. The EORTC QoL questionnaire-C30 (EORTC QLQ-C30)version 3.0 will be used. This questionnaire comprises 30 questions, 24 of which are aggregated into nine multi-question scales, that is, five functioning scales (e.g., physical), three symptom scales (e.g., fatigue) and one global health status scale. The remaining six single-question (e.g., dyspnoea) scales assess symptoms. These 15 scales will be scored according to the official Scoring Manual.
- Event-free survival (EFS) within different subgroups [ Time Frame: 3 years ]analyses for EFS will be performed within the following subgroups: Epstein-Barr virus (EBV) DNA (<4000copies/ml vs. ≥4000copies/ml), different PD-L1 expression levels (<1% vs. ≥1%), tertiary lymphoid structure (+ vs. -), age, gender, performance status, T category, N category, and stage (III vs. IVA).
- The association of circulation autoimmune antibodies with immune-related adverse events [ Time Frame: 1 year ]
- The association of circulation cytokines, chemokines, and growth factors/regulators with immune-related adverse events [ Time Frame: 1 year ]
- The association of gene expression with the efficacy of sintilimab [ Time Frame: 3 years ]RNA sequencing will be conducted using baseline tumor samples.
- The association of cell populations with the efficacy of sintilimab [ Time Frame: 3 years ]Multiplex Immunofluorescence will be conducted to assess tumor and immune-related markers in baseline tumor samples.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years to 65 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Patients with histologically confirmed nasopharyngeal carcinoma.
- Tumor staged as III-IVA (AJCC 8th, except T3N0-1 or T4N0).
- Eastern Cooperative Oncology Group performance status ≤1.
- Adequate marrow function: neutrocyte count≥1.5×10e9/L, hemoglobin ≥90g/L and platelet count ≥100×10e9/L.
- Alanine Aminotransferase (ALT)/Aspartate Aminotransferase (AST) ≤2.5×upper limit of normal (ULN), and bilirubin ≤ 1.5×ULN.
- Adequate renal function: creatinine clearance rate ≥ 60 ml/min (Cockcroft-Gault formula).
- Patients must be informed of the investigational nature of this study and give written informed consent.
- Women of childbearing potential (WOCBP) who are sexually active must be willing to adhere to effective contraception during treatment and for 1 year after the last dose of study drug. Men who are sexually active with WOCBP must be willing to adhere to effective contraception during treatment and for 1 year after the last dose of the study drug.
Exclusion Criteria:
- Age > 65 or < 18.
- Hepatitis B surface antigen (HBsAg) positive and hepatitis B virus DNA >1×10e3 copies/ml or 200IU/ml
- Hepatitis C virus (HCV) antibody positive
- Has active autoimmune disease, except type I diabetes, hypothyroidism treated with replacement therapy, and skin disease that doesn't require systemic treatment (e.g., vitiligo, psoriasis, or alopecia).
- Has any condition that required systemic corticosteroid (equivalent to prednisone >10mg/d) or other immunosuppressive therapy within 28 days before informed consent. Patients received systemic corticosteroid equivalent to prednisone ≤10mg/d, inhale or topical corticosteroid will be allowed.
- Has a known history of active TB (bacillus tuberculosis) within 1 year; patients with adequately treated active TB over 1 year ago will be allowed.
- Has a known history of interstitial lung disease.
- Has received a live vaccine within 30 days before informed consent or will receive a live vaccine in the near future.
- Is pregnant or breastfeeding.
- Prior malignancy within 5 years, except in situ cancer, adequately treated non-melanoma skin cancer, and papillary thyroid carcinoma.
- Has known allergy to large molecule protein products or any compound of sintilimab.
- Has a known history of human immunodeficiency virus (HIV) infection.
- Any other condition, including symptomatic heart failure, unstable angina, myocardial infarction, active infection requiring systemic therapy, mental illness or domestic/social factors, deemed by the investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interferes with the interpretation of the results.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03700476
China, Guangdong | |
First People's Hospital of Foshan | |
Foshan, Guangdong, China | |
Panyu central hospital | |
Guangzhou, Guangdong, China, 510060 | |
SUN YAT-SEN UNIVERSITY cANCER CENTER | |
Guangzhou, Guangdong, China, 510060 | |
China, Guangxi | |
Cancer Hospital of Guangxi Medical University | |
Nanning, Guangxi, China | |
China, Guizhou | |
Cancer Hospital of Guizhou Medical University | |
Guiyang, Guizhou, China | |
China, Hubei | |
Union Hospital Affiliated with Tongji Medical College of Huazhong University of Science and Technology | |
Wuhan, Hubei, China | |
China, Hunan | |
Xiangya Hospital Central South University | |
Changsha, Hunan, China | |
China, Shanxi | |
Xijing Hospital, Fourth Military Medical University | |
Xi'an, Shanxi, China | |
China, Sichuan | |
West China Hospital, Sichuan University | |
Chengdu, Sichuan, China |
Principal Investigator: | Jun Ma, MD | Sun Yat-sen University |
Responsible Party: | Jun Ma, MD, Professor, Sun Yat-sen University |
ClinicalTrials.gov Identifier: | NCT03700476 |
Other Study ID Numbers: |
2018-FXY-135-FLK |
First Posted: | October 9, 2018 Key Record Dates |
Last Update Posted: | March 28, 2023 |
Last Verified: | March 2023 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Yes |
Plan Description: | Complete de-identified patient data set |
Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) Analytic Code |
Time Frame: | For 2 years started from 12 months after publication of the primary trial report. |
Access Criteria: | Authoritative researchers who provide a methodologically sound proposal for individual participant data meta-analysis. |
Studies a U.S. FDA-regulated Drug Product: | No |
Studies a U.S. FDA-regulated Device Product: | No |
Nasopharyngeal Carcinoma Nasopharyngeal Neoplasms Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Pharyngeal Neoplasms Otorhinolaryngologic Neoplasms Head and Neck Neoplasms Neoplasms by Site |
Nasopharyngeal Diseases Pharyngeal Diseases Stomatognathic Diseases Otorhinolaryngologic Diseases Gemcitabine Antineoplastic Agents Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action |