- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04605562
Umbrella Biomarker-Guided Therapy in NPC
September 2, 2021 updated by: Jun Ma, MD, Sun Yat-sen University
Precision Treatment of Locoregionally Advanced Nasopharyngeal Carcinoma Based on Molecular Immune Subtyping: an Umbrella Trial
This is a phase 2, open-label, umbrella study, with the purpose to evaluate the therapeutic efficacy and safety of chemoradiotherapy in combination with immunotherapy and/or targeted treatment in high-risk locoregionally advanced nasopharyngeal carcinoma.
The specific grouping of patients' depends on the SYSUCC immune subtyping based on 100+ gene panel testing.
Study Overview
Status
Not yet recruiting
Conditions
Detailed Description
This is a phase 2, open-label, umbrella study, with the purpose to evaluate the therapeutic efficacy and safety of chemoradiotherapy in combination with immunotherapy and/or targeted treatment in high-risk locoregionally advanced nasopharyngeal carcinoma.
The specific grouping of patients' depends on the SYSUCC immune subtyping based on 100+ gene panel testing.
The molecular subgroups include the Active, Evaded and non-Immune Subtypes.
New treatment arms may be added and/or existing treatment arms may be closed during the study course on the basis of ongoing efficacy and safety as well as the current treatments available.
Study Type
Interventional
Enrollment (Anticipated)
206
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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Guangdong
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Guangzhou, Guangdong, China, 510060
- Sun Yat-sen University Cancer Center
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 65 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Age: 18 to 65;
- Pathological type: non-keratinizing carcinoma (World Health Organization criteria);
- Diagnosed with LANPC (T4N1, T1-4N2-3) according to the 8th edition clinical staging system of the American Joint Committee on Cancer [AJCC]/Union for International Cancer Control [UICC];
- ECOG performance score: 0 to 1;
- Normal bone marrow function: white blood cell count > 4×109/L, hemoglobin > 90g/L, platelet count > 100×109/L;
- Normal values of thyroid function, amylase and lipase examination, pituitary function, inflammation and infection indicators, myocardial enzymes, and ECG results. For patients older than 50 years with a smoking history, normal lung function are required. Patients with abnormal ECG and/or a history of vascular disease (but not meeting the exclusion criteria listed in the exclusion criteria 7) need further testing and require normal results of myocardial function and color Doppler ultrasound.
- Normal liver and kidney function: total bilirubin ≤ 1.5 × upper limit of normal (ULN); alanine transaminase and aspartate transaminase ≤ 2.5 × ULN; alkaline phosphatase ≤ 2.5 × ULN; creatinine clearance rate ≥ 60 ml/min;
- Patients must sign informed consent and be willing and able to comply with the requirements of visits, treatment, laboratory tests and other research requirements stipulated in the research schedule;
- Subjects with pregnancy ability must agree to use reliable contraceptive measures from screening to 1 year after treatment.
Exclusion Criteria:
- Hepatitis B virus surface antigen (HBsAg) positive and HBV DNA > 1×10E3 copies/ml; anti-hepatitis C virus positive;
- Anti-human immunodeficiency virus (HIV) positive or diagnosed with acquired immune deficiency syndrome (AIDS);
- Active tuberculosis: active tuberculosis in the past 1 year should be excluded regardless with treatment; history of active tuberculosis over 1 year should be excluded except that previous regulatory anti-tuberculosis treatment is proved;
- Active, known or suspected autoimmune disease (including but not limited to uveitis, enteritis, hepatitis, pituitary, nephritis, vasculitis, hyperthyroidism, hypothyroidism and asthma requiring bronchiectasis). Exceptions are type I diabetes mellitus, hypothyroidism requiring hormone replacement therapy, skin disorders requiring no systemic treatment (such as vitiligo, psoriasis or alopecia);
- Previous interstitial lung disease or pneumonia requiring oral or intravenous steroid therapy;
- Chronic treatment with systemic glucocorticoid (dose equivalent to or over 10 mg prednisone per day) or any other form of immunosuppressive therapy. Subjects who used inhaled or topical corticosteroids were eligible;
- Uncontrolled heart disease, for example: 1) heart failure (NYHA level ≥ 2); 2) unstable angina; 3) myocardial infarction in past 1 year; 4) supraventricular or ventricular arrhythmia requiring treatment or intervention;
- Pregnant or lactating women (pregnancy test should be considered for women with sexual life and fertility);
- Previous or concurrent with other malignant tumors, except for adequately treated non-melanoma skin cancer, cervical carcinoma in situ and thyroid papillary cancer;
- Allergy to macromolecular protein preparations, or any component of the intervention drugs;
- Active infection requiring systemic treatment;
- History of organ transplantation;
- History of psychotropic disease, alcoholism or drug abuse; other situation assessed by the investigators that may compromise the safety or compliance of patients, such as serious disease requiring timely treatment (including mental illness), severe laboratory abnormalities, or family-social risk factors.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: IC+CCRT with palbociclib
If patients were non-Immune Subtype.
|
Administered orally
Gemcitabine as induction chemotherapy, 1000 mg/m2 day 1, 8 per cycle, every 3 weeks for 3 cycles; induction cisplatin 80mg/m2, every 3 weeks for 3 cycles before radiation; concurrent cisplatin 100mg/m2, every 3 weeks for 2 cycles during radiation
Definitive IMRT of 70 Gy, 33 fractions, 5 fractions/week, 1 fraction/day
|
Experimental: IC+CCRT with galunisertib and PD-1 blocking antibody
If patients were Evaded Immune Subtype.
|
Administered orally
Gemcitabine as induction chemotherapy, 1000 mg/m2 day 1, 8 per cycle, every 3 weeks for 3 cycles; induction cisplatin 80mg/m2, every 3 weeks for 3 cycles before radiation; concurrent cisplatin 100mg/m2, every 3 weeks for 2 cycles during radiation
Definitive IMRT of 70 Gy, 33 fractions, 5 fractions/week, 1 fraction/day
Administered every 3 weeks
|
Experimental: IC+CCRT with PD-1 blocking antibody
If patients were Active Immune Subtype.
|
Gemcitabine as induction chemotherapy, 1000 mg/m2 day 1, 8 per cycle, every 3 weeks for 3 cycles; induction cisplatin 80mg/m2, every 3 weeks for 3 cycles before radiation; concurrent cisplatin 100mg/m2, every 3 weeks for 2 cycles during radiation
Definitive IMRT of 70 Gy, 33 fractions, 5 fractions/week, 1 fraction/day
Administered every 3 weeks
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Failure-free survival (FFS)
Time Frame: 3-year
|
Failure-free survival is measured from day of diagnosis until treatment failure, death from any cause, or last follow-up visit, whichever occurred first
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3-year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall survival (OS)
Time Frame: 3-year
|
Overall survival is measured from day of diagnosis until death due to any cause or the latest known date alive
|
3-year
|
Distant failure-free survival (DFFS)
Time Frame: 3-year
|
Distant failure-free survival is measured from day of diagnosis until distant metastasis
|
3-year
|
Incidence rate of investigator-reported adverse events (AEs)
Time Frame: 3-year
|
Analysis of investigator-reported adverse events (AEs) are based on treatment-related AEs (trAEs) and immune-related AEs (irAEs), and all-grade AEs and grade 3-4 AEs.
AEs are evaluated by investigators according to the Common Terminology Criteria for Adverse Events, version 5.0
|
3-year
|
Incidence rate of patient-reported adverse events (AEs)
Time Frame: 3-year
|
Analysis of patient-reported adverse events (AEs) are based on treatment-related AEs (trAEs) and immune-related AEs (irAEs), and all-grade AEs and grade 3-4 AEs.
AEs are evaluated by patients themselves
|
3-year
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Anticipated)
June 1, 2022
Primary Completion (Anticipated)
December 1, 2026
Study Completion (Anticipated)
December 1, 2026
Study Registration Dates
First Submitted
October 22, 2020
First Submitted That Met QC Criteria
October 22, 2020
First Posted (Actual)
October 28, 2020
Study Record Updates
Last Update Posted (Actual)
September 5, 2021
Last Update Submitted That Met QC Criteria
September 2, 2021
Last Verified
September 1, 2021
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Pharyngeal Neoplasms
- Otorhinolaryngologic Neoplasms
- Head and Neck Neoplasms
- Nasopharyngeal Diseases
- Pharyngeal Diseases
- Stomatognathic Diseases
- Otorhinolaryngologic Diseases
- Nasopharyngeal Neoplasms
- Carcinoma
- Nasopharyngeal Carcinoma
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Immunologic Factors
- Protein Kinase Inhibitors
- Antibodies
- Antibodies, Blocking
- Palbociclib
Other Study ID Numbers
- SZR2019-069
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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