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Completed

NCT Number: NCT03924986

Tislelizumab Combined With Chemotherapy Versus Chemotherapy Alone in Recurrent or Metastatic Nasopharyngeal Cancer (NPC)

This study was designed to compare the efficacy and safety of tislelizumab (BGB-A317) combined with gemcitabine plus cisplatin versus placebo combined with gemcitabine plus cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal cancer.

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Key information

Conditions

Recurrent or Metastatic Nasopharyngeal Cancer Disease Attributes Head and Neck Neoplasms Nasopharyngeal Diseases Nasopharyngeal Neoplasms Neoplasms Neoplasms by Site Otorhinolaryngologic Diseases Otorhinolaryngologic Neoplasms Pathologic Processes Pathological Conditions, Signs and Symptoms Pharyngeal Diseases Pharyngeal Neoplasms Recurrence Stomatognathic Diseases

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Anhui Provincial Hospital, Hefei, Anhui, China

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Key Inclusion Criteria:

  • Able to provide written informed consent and can understand and agree to comply with the requirements of the study and the schedule of assessments
  • Aged between 18 to 75 years on the day of signing the informed consent form (or the legal age of consent in the jurisdiction in which the study is taking place)
  • Histologically or cytologically confirmed, recurrent or metastatic NPC
  • Participants must be able to provide fresh or archival tumor tissues (formalin-fixed paraffin-embedded [FFPE] blocks or approximately 10 [≥ 6] freshly cut unstained FFPE slides) with an associated pathological report. The archival tumor tissues must be collected within 2 years before screening. In the absence of sufficient archival tumor tissues, a fresh biopsy of a tumor lesion at baseline is mandatory
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
  • Must have ≥ 1 measurable lesions as defined per RECIST v1.1
  • Must be treatment-naive for recurrent or metastatic NPC.

Key Exclusion Criteria:

  • Participants with locally recurrence suitable for curative surgery or radiotherapy
  • Received any approved systemic anticancer therapy, including hormonal therapy, within 28 days prior to initiation of study treatment. The following exception is allowed:
  • Palliative radiotherapy for bone metastases or soft tissue lesions should be completed > 7 days prior to baseline imaging.
  • Has received any immunotherapy (including but not limited to interferons, interleukin 2, tumor necrosis factor interleukin, and thymoxin) or any investigational therapies within 14 days or 5 half-lives (whichever is longer) of randomization
  • Received prior therapies targeting programmed cell death protein-1 (PD-1) or programmed cell death protein ligand-1 (PD-L1)
  • Active leptomeningeal disease or uncontrolled, untreated brain metastasis
  • Active autoimmune diseases or history of autoimmune diseases that may relapse
  • Any active malignancy ≤ 2 years before randomization except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated curatively (eg, resected basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast)

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Treatment and study plan

Tislelizumab

Drug

200 mg intravenously (IV) once every 3 weeks (Q3W)

Other names: BGB-A317

Placebo

Drug

Placebo to match tislelizumab (administered intravenously Q3W)

Gemcitabine

Drug

1 gram per square meter of body surface area (g/m^2) on Day 1 and day 8 of each cycle, administered as an IV infusion within 30 minutes, for 4 to 6 cycles

Cisplatin

Drug

80 milligrams per square meter of body surface area (mg/m^2) on Day 1 of each cycle, administered as an IV infusion for over 4 hours if possible or with proper infusion time based on local clinical guidelines or clinical practice and according to the treating physician's clinical judgment, for 4 to 6 cycles.

Primary outcomes

  1. Progression-free Survival as Assessed by the Independent Review Committee (IRC)

    Time frame: Through the study interim data analysis cutoff date of March 26th, 2021 (maximum time on study follow-up was 23 months)

    Defined as the time from randomization to the first objectively documented disease progression, or death from any cause, whichever occurred first, as assessed by the IRC per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Kaplan-Meier methodology was used to estimate the median PFS.

Secondary outcomes

  1. Overall Response Rate (ORR) as Assessed by the IRC

    Time frame: Through the study interim data analysis cutoff date of March 26th, 2021 (maximum time on study follow-up was 23 months)

    Defined as the percentage of participants who had complete response or partial response as assessed by the IRC per RECIST v1.1 in all randomized participants with measurable disease at Baseline.

  2. Duration of Response (DOR) as Assessed by the IRC

    Time frame: Through the study interim data analysis cutoff date of March 26th, 2021 (maximum time on study follow-up was 23 months)

    Defined as the time from the first occurrence of a documented objective response to the time of relapse, or death from any cause, whichever occurred first, as assessed by the IRC per RECIST v1.1 in all randomized participants with documented objective responses.

  3. Overall Survival (OS) as Assessed by the IRC

    Time frame: Through study completion data cut-off date of December 8th, 2023 or last available date showing participants alive (maximum time on study follow-up was 53 months)

    Defined as the time from the date of randomization to the date of death due to any cause.

  4. PFS as Assessed by the Investigator

    Time frame: Through the interim analysis data cut-off date of March 26th, 2021 (up to approximately 23 months)

    Defined as the time from randomization to the first objectively documented disease progression, or death from any cause, whichever occurred first, as assessed by the investigator per RECIST v1.1.

  5. Progression-free Survival After Next Line of Treatment (PFS2) as Assessed by the Investigator

    Time frame: Through the study completion data cut-off date of December 8th, 2023 (maximum time on study follow-up was 53 months)

    Defined as the time from randomization to second/subsequent disease progression after initiation of new anticancer therapy, or death from any cause, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method.

  6. Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Global Health Status

    Time frame: Baseline to Cycle 6 (Each cycle is 21 days)

    Change from baseline in EORTC QLQ-C30 Global Health Status/Quality of Life score. The EORTC QLQ-C30 v3.0 is a questionnaire that assesses quality of life of participants with cancer. It includes global health status and quality of life questions related to overall health in which participants respond based on a 7-point scale, where 1 is very poor and 7 is excellent. Raw scores are transformed into a 0 to 100 scale via linear transformation. A higher score indicates better health outcomes.

  7. Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Head and Neck-351 (EORTC QLQ-H&N35) Index Score

    Time frame: Baseline to Cycle 6 (Each cycle is 21 days)

    The QLQ-H&N35 consists of thirty-five questions that are associated with eighteen symptom scales (pain, swallowing, senses, speech, social eating, social contact, sexuality, problem with teeth, problem opening mouth, dry mouth, problem with sense smell, cough, felt ill, pain med, nutritional supplements, feeding tube, weight loss and weight gain).. Raw scores are transformed into a 0 to 100 scale via linear transformation. The index score is calculated as an average of the 18 symptom scales. A negative change from baseline score indicates improvement in symptoms.

  8. Number of Participants With Adverse Events

    Time frame: From first dose to 30 days after last dose or new anticancer therapy, or until Dec 8, 2023 data cut-off; max treatment duration: 231 weeks (Arm A), 202 weeks (Arm B).

    Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), including laboratory tests, vital signs, electrocardiograms (ECGs), and physical examinations (PEs ), graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. For Arm B, only adverse events reported prior to participants crossing over to receive tislelizumab monotherapy are included.

Sponsors and collaborators

Lead sponsor

BeiGene

Industry

Registry information

Official study title

A Phase 3, Multicenter, Double-Blind, Randomized, Placebo-Controlled Study to Compare the Efficacy and Safety of Tislelizumab (BGB-A317) Combined With Gemcitabine Plus Cisplatin Versus Placebo Combined With Gemcitabine Plus Cisplatin as First-Line Treatment for Recurrent or Metastatic Nasopharyngeal Cancer

Acronym: RATIONALE-309

Important dates

Study start
2019
Primary completion
2021
Study completion
2023
First posted
Apr 23, 2019
Registry last updated
Jan 31, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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