A pilot study of Nivolumab with stereotactic ablative radiation therapy after induction chemotherapy in cholangiocarcinoma.
- Conditions
- ocally Advanced, recurrent or metastatic cholangiocarcinoma.biliary tract
- Registration Number
- LBCTR2020124689
- Lead Sponsor
- American University of Beirut
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- All
- Target Recruitment
- 40
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
oAn estimated life expectancy of more than 3 months.
6)Have adequate hematologic and biochemical function by meeting the following:
oTotal bilirubin acceptable level = 1.5 × the institutional upper limit of normal (ULN) range;
oAspartate aminotransferase (AST) and alanine aminotransferase (ALT) acceptable levels up to 5 x ULN range;
oSerum urea and serum creatinine acceptable levels up to 1.5 x ULN range;
oCalculated 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.
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 understa
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method ame: 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;Timepoints: at 8 months from first nivolumab dose ;Measure: Kaplan-Meier methods
- Secondary Outcome Measures
Name Time Method ame: evaluate the overall survival (OS) rate ;Timepoints: every 3 months after progression ;Measure: Kaplan-Meier ;Name: Tumor response rates at the primary and secondary sites ;Timepoints: after each 4rth cycle of Nivolumab until progression ;Measure: descriptive RECIST 1.1 ;Name: duration of response at non-irradiated tumor sites in;Timepoints: : every 4 months from the date of first treatment visit until the date of first documented progression,;Measure: descriptive ;Name: Evaluate the following biomarkers: CD3+, CD4+, and CD8+ , and changes in PD-L1 expression at baseline and following first cycle of Nivolumab and radiotherapy ;Timepoints: at Baseline visit and at Day 22 ;Measure: quantification ;Name: Assess the Quality of life ;Timepoints: on each visit ;Measure: FACT -HEP questionnaire