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Trial details
A pilot study of Nivolumab with stereotactic ablative radiation therapy after induction chemotherapy in cholangiocarcinoma.
Current status:
Approved
|
Date registered:
21/03/2021
|
Date last updated:
28/01/2021
Trial version(s)
Current: 16/12/2020
Click here to view the tips and fields' descriptions
Main Information
Primary registry identifying number
LBCTR2020124689
Protocol number
CA209-7DJ/BIO-2019-0447
MOH registration number
Trial already registered with the MoPH
Study registered at the country of origin
Type of registration
Prospective
Date of registration in national regulatory agency
16/12/2020
Primary sponsor
American University of Beirut
Primary sponsor: Country of origin
lebanon
Public title
A pilot study of Nivolumab with stereotactic ablative radiation therapy after induction chemotherapy in cholangiocarcinoma.
Acronym
N/A
Scientific title
A pilot study of Nivolumab with stereotactic ablative radiation therapy after induction chemotherapy in cholangiocarcinoma.
Acronym
N/A
Brief summary of the study: English
This is a phase II open-label, single-arm, multicenter pilot study investigating the efficacy and safety of Nivolumab treatment followed by SBRT radiation treatment, then monthly Nivolumab in patients with non-resectable locally-advanced, metastatic or recurrent intra-hepatic or extra-hepatic cholangiocarcinoma. Primary Study Objectives: - evaluate the progression free survival (PFS) at 8 months and the disease control rate in patients with non-resectable locally-advanced or metastatic or recurrent intra-hepatic or extra-hepatic cholangiocarcinoma following Nivolumab/SBRT treatment. Secondary Study objectives: - Evaluate the overall survival (OS) rate in patients with advanced intra-hepatic or extra-hepatic cholangiocarcinoma following Nivolumab/SBRT treatment. - evaluate the two-year survival in patients with advanced intra-hepatic or extra-hepatic cholangiocarcinoma following Nivolumab/SBRT treatment. - Evaluate tumor response rates at the primary and secondary sites using RECIST1.1 criteria as well as the duration of response at un-irradiated tumor sites in patients with Stage IV disease. - evaluate the following biomarkers: CD3+, CD4+, and CD8+ T cell infiltration, and changes in PDL-1 expression following 1 cycle Nivolumab and SBRT. - assess the safety and tolerability of Nivolumab/SBRT according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAEv5). - Assess the quality of life of the patients through completed FACT-G questionnaires. Methodology: Eligible patients with radiological partial response rate or stable disease following 4 cycles of Cisplatin/ Gemcitzbine will be enrolled. Those patients will receive Nivolumab intravenously every 4 weeks until disease progression or until they experience unacceptable drug related serious adverse event (SAE). Patients’ disease status will be evaluated by CT chest, abdomen and pelvis (RECIST 1.1) criteria after each 4 cycles of Nivolumab. Enrolled patients will be followed until death. Neither reference therapy, nor placebo nor control group will be added to the trial. Neither randomization nor blinding will be used in this trial. Approximately, 40 patients will be accrued from 4 sites over a period of 1 year. Risks/benefits Potential risks of this study: Small risk of radiation therapy and immune-related adverse events associated with Nivolumab (typically occurring in less than 10% of patients and mild/reversible however more significant immune-related adverse events are possible). Potential benefits: Improvement in response rate and chance of cure and potential benefit to future patients with locally advanced and metastatic cholangiocarcinoma patients.
Brief summary of the study: Arabic
دراسة تجريبية من المرحلة الثانية، مفتوحة التسمية، ذات ذراع واحد، متعدّدة المراكز لتقييم فعالية وسلامة نيفولوماب مع العلاج الشعاعي التجسيمي التجزيئي بعد العلاج الكيميائي التعريفي ضد سرطان الأوعية الصفراوية. تهدف هذه الدراسة السريرية إلى تقييم فعاليّة وسلامة الجمع بين جرعة مرتفعة من العلاج الشعاعي والعلاج المناعي (نيفولوماب) لمعالجة المرض الذي تعاني منه والمعروف بإسم سرطان الأوعية الصفراوية. سيتم تسجيل المرضى المؤهلين الذين لديهم معدل استجابة جزئية إشعاعية أو مرض مستقر بعد 4 دورات علاجية من Cisplatin / Gemcitabine. سيتلقى هؤلاء المرضى Nivolumab عن طريق الوريد كل 4 أسابيع حتى تطور المرض أو حتى يواجهوا حدثًا ضارًا خطيرًا غير مقبول مرتبط بالعقاقير (SAE). سيتم تقييم حالة المرض لدى المرضى من خلال معايير تصوير مقطعي محوسب للصدر والبطن والحوض (RECIST 1.1) بعد كل 4 دورات من Nivolumab. سيتم متابعة المرضى المسجلين حتى الوفاة. لن يتم إضافة العلاج المرجعي أو العلاج الوهمي أو المجموعة الضابطة إلى التجربة. لن يتم استخدام التعشية أو التعمية في هذه التجربة. تقريبًا ، سيتم تجميع 40 مريضًا من 4 مواقع على مدار عام واحد. المخاطر المحتملة لهذه الدراسة: خطر ضئيل من العلاج الإشعاعي. والأحداث المرتبطة بـ Nivolumab (تحدث عادةً في أقل من 10 ٪ من المرضى وخفيفة / قابلة للعكس ولكن من الممكن حدوث أحداث سلبية ذات صلة بالمناعة أكثر أهمية). الفوائد المحتملة: تحسين معدل الاستجابة وفرصة الشفاء وإحتمال الفوائد للمرضى المستقبليين المصابين بسرطان القنوات الصفراوية المتقدم.
Health conditions/problem studied: Specify
Locally Advanced, recurrent or metastatic cholangiocarcinoma.
Interventions: Specify
Experimental arm : locally advanced, metastatic or recurrent cholangiocarcinoma Day 1: Nivolumab treatment Day 8: radiotherapy 3 to 5 fractions SBRT Day 20: CT guided Biopsy Day 28: Nivolumab treatment 480 mg IV drip Monthly treatment Nivolumab CT scan chest abdomen and pelvis: after each 4 Doses
Key inclusion and exclusion criteria: Inclusion criteria
Inclusion criteria: 1) Signed and dated informed consent form. 2) Patients aged ≥18 years. 3) Pathologically (histologically or cytologically) and radiologically confirmed diagnosis of non-resectable locally advanced or metastatic or recurrent intrahepatic or extrahepatic CCA within 90 days of registration. 4) Patients who have stable disease or partial response following 4 cycles of cisplatin/gemcitabine. 5) ECOG performance score <3 o An estimated life expectancy of more than 3 months. 6) Have adequate hematologic and biochemical function by meeting the following: o Total bilirubin acceptable level ≤ 1.5 × the institutional upper limit of normal (ULN) range; o Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) acceptable levels up to 5 x ULN range; o Serum urea and serum creatinine acceptable levels up to 1.5 x ULN range; o Calculated glomerular filtration rate ≥ 45 mL/min according to the Chronic Kidney Disease Epidemiology Collaboration equation (or local institutional standard method). 7) Negative serum or urine pregnancy test at screening for women of childbearing potential who are sexually active. 8) Highly effective contraception for both males and females of child-bearing potential who are sexually active throughout the study and for at least 5 months and 7 months after the last Nivolumab treatment administration, respectively. 9) Candidate for percutaneous biopsy as per tumor location evidenced by CT scan and interventional radiologist.
Key inclusion and exclusion criteria: Gender
Both
Key inclusion and exclusion criteria: Age minimum
18
Key inclusion and exclusion criteria: Age maximum
90
Key inclusion and exclusion criteria: Exclusion criteria
Exclusion Criteria: 1. Patients who have progression following 4 cycles of cisplatin/ gemcitabine evidenced by CT scan as per RECIST 1.1. 2. Active brain metastases or leptomeningeal metastases. 3. Prior organ transplantation or allogenic stem-cell transplantation. 4. Known prior severe hypersensitivity to IMP or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI-CTCAE v4.03 Grade ≥ 3). 5. Active infection requiring systemic therapy within 28 days before the first dose of study treatment (e.g., urinary tract infection). 6. Known history of testing positive for the human immunodeficiency virus or known acquired immunodeficiency syndrome. 7. Evidence of liver cirrhosis. 8. Current use of immunosuppressive medication, except for the following: • Intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); • Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; • Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication). 9. Active autoimmune diseases that might deteriorate upon receiving an immune-stimulatory agent. 10. Conditions such as vitiligo, psoriasis, diabetes type I, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible. 11. Commonly excluded conditions include: Addison’s disease, thyroiditis/ Hashimoto’s thyroiditis, systemic lupus erythematosus, Sjogren’s syndrome, scleroderma, myasthenia gravis, Goodpasture’s syndrome, and Grave’s disease 12. Hepatic insufficiency manifesting as clinical jaundice, hepatic encephalopathy, and/or variceal bleed within 60 days prior to study entry. 13. Transmural myocardial infarction within 6 months of enrollment; provided that anti-platelets cannot be stopped to perform percutaneous biopsy. 14. Congestive heart failure (≥ New York Heart Association Classification Class II) requiring hospitalization within the last 6 months provided that anti-platelets cannot be stopped to perform percutaneous biopsy. 15. Serious cardiac arrhythmia requiring medical treatment provided that anti-platelets cannot be stopped to perform percutaneous biopsy. 16. Recent cerebral vascular accident/stroke within 6 months of enrollment provided that anti-platelets cannot be stopped to perform percutaneous biopsy. 17. End-stage renal disease requiring dialysis. 18. Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis, or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior. 19. Vaccination within 4 weeks of the first dose of BMS-936558 and while on trial is prohibited except for administration of inactivated vaccines. 20. Treatment with an investigational agent within 28 days before the first dose of study treatment. 21. Prior treatment with any drug or antibody (anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody) targeting T cell costimulation or checkpoint pathways. 22. Patients suspected by the physician that he/she will not be compliant to the protocol conduct. 23. Pregnant women are excluded from this study; breastfeeding should be discontinued. 24. Patients participating in another clinical trial. 25. Patients not willing to sign the consent form. 26. Any psychiatric condition that would prohibit the understanding or rendering of informed consent. 27. Legal incapacity or limited legal capacity patients receiving other oncology specific medication not authorized in the protocol.
Type of Study
Type
Interventional
Type of intervention
Pharmaceutical
Trial scope
Therapy
Trial scope: Specify scope
Study design: Allocation
Single Arm Study
Study design: Masking
Open (masking not used)
Study design: Control
Historical
Study phase
2
Study design: Purpose
Treatment
Study design: Assignment
Single
IMP has market authorization
Yes, Lebanon
Name of IMP
Nivolumab
Year of authorization
2015
Month of authorization
12
Type of IMP
Immunological
Pharmaceutical class
Immunotherapy
Therapeutic indication
locally advanced, recurrent, metastatic cholangiocarcinoma
Therapeutic benefit
The combination of Nivolumab and SBRT following chemotherapy will improve outcomes of cholangiocarcinoma patients including progression free survival and and disease control rate.
Biospecimen retention
Samples without DNA
Biospecimen description
tissue samples
Target sample size
40
Actual enrollment target size
Date of first enrollment: Type
Anticipated
Date of first enrollment: Date
15/02/2021
Date of study closure: Type
Anticipated
Date of study closure: Date
15/02/2024
Recruitment status
Pending
Date of completion
IPD sharing statement plan
Yes
IPD sharing statement description
Patient data will be kept strictly confidential and patient anonymity will be protected by using number codes and initials. The Principal Investigator, the CRO and the Health Authorities will not disclose any personal patient information. Bristol-Myers Squibb will not have access to identified patients’ data and samples. Data processing, from data collection to database lock, will be carried out in accordance with GCP. The database and data entry screens will be created in software specifically designed for clinical data management in compliance with ICH-GCP requirements. The study data are the property of the Principal Investigator. The co-Principal Investigator, co-investigators and any of the research team shall obtain written approval from the Principal Investigator prior to the publication/communication of the results of any work carried out during or in relation to the study. Publication and/or communication of the results of the clinical study is the responsibility of the Principal Investigator. It will be of a cooperative nature involving authors representing the Principal Investigator, the Co-Principal Investigator and Co-Investigators and the scientific committee, if any.
Additional data URL
N/A
Summary Results
Secondary Identifying Numbers
Full name of issuing authority
Secondary identifying number
clinicalTrials.gov
NCT04648319
Sources of Monetary or Material Support
Name
Bristol Myers Squibb
Secondary Sponsors
Name
NA
Contact for Public/Scientific Queries
Contact type
First name
Last name
Address
Country
Telephone
Email
Affiliation
Public
Ali
Shamseddine
American University of Beirut Medical Center P.o.Box : 11-0236 Riad El Solh : 110 72020
Lebanon
01350000
as04@aub.edu.lb
American University of Beirut
Scientific
Ali
Shamseddine
American University of Beirut Medical Center P.o.Box : 11-0236 Riad El Solh : 110 72020
Lebanon
01350000
as04@aub.edu.lb
American University of Beirut
Centers/Hospitals Involved in the Study
Center/Hospital name
Name of principles investigator
Principles investigator speciality
Ethical approval
American University of Beirut Medical Center
Dr. ALi Shamseddine
Professor of medicine/hematology-Oncology
Approved
Institut Jule Bordet
Dr. Alain Hendlizs
Professor of Medicine/GI oncology
Pending
Cliniques universitaires Saint-Luc
Dr. Ivan Borbath
Professor of Medicine/GI oncology
Pending
Centre hospitalier de Luxembourg
Dr. Guy Berchem
Professor of Medicine/medical oncologist
Pending
Ethics Review
Ethics approval obtained
Approval date
Contact name
Contact email
Contact phone
American University of Beirut Medical Center
22/10/2020
Dr. Ali Shamseddine
as04@aub.edu.lb
961-1-350000 (ext:5390)
Countries of Recruitment
Name
Lebanon
Belgium
Luxembourg
Health Conditions or Problems Studied
Condition
Code
Keyword
cholangiocarcinoma
Malignant neoplasm of other and unspecified parts of biliary tract (C24)
biliary tract
Interventions
Intervention
Description
Keyword
Nivolumab at day 1 and then monthly Nivolumab until progression
day 1 and then monthly Nivolumab until progression
Nivolumab
radiotherapy
30 grays of 3 to 5 fractions of high dose SBRT at day 8
SBRT
CT guided biopsy
at day 22 after first dose of Nivolumab and radiotherapy to assess
will evaluate PD-L1 expression and on tumor cells and infiltrating immune T cells.
CT scan Abdomen and Pelvis
CT scan CAP will be dpne after each 4rth cycle of Novolumab to assess tumor response using RECIST 1.1
Tumor response evaluation
Primary Outcomes
Name
Time points
Measure
assess the median progression free survival (PFS) and PFS rate and DCR in patients with non-resectable locally-advanced or metastatic or recurrent intrahepatic or extrahepatic CCA following Nivolumab/SBRT treatment
at 8 months from first nivolumab dose
Kaplan-Meier methods
Key Secondary Outcomes
Name
Time points
Measure
evaluate the overall survival (OS) rate
every 3 months after progression
Kaplan-Meier
Tumor response rates at the primary and secondary sites
after each 4rth cycle of Nivolumab until progression
descriptive RECIST 1.1
duration of response at non-irradiated tumor sites in
: every 4 months from the date of first treatment visit until the date of first documented progression,
descriptive
Evaluate the following biomarkers: CD3+, CD4+, and CD8+ , and changes in PD-L1 expression at baseline and following first cycle of Nivolumab and radiotherapy
at Baseline visit and at Day 22
quantification
Assess the Quality of life
on each visit
FACT -HEP questionnaire
Trial Results
Summary results in Lebanon
Study results globally
Date of posting of results summaries
Date of first journal publication of results
Results URL link
Baseline characteristics
Participant flow
Adverse events
Outcome measures
URL to protocol files
Link(s) to publications related to the study
Changes History
Change
Date
Download as PDF
Save a PDF copy of the summary of the trial