A Study of BMS-936558 With SBRT After Induction Chemotherapy in Cholangiocarcinoma

NCT04648319 | Terminated Phase 2 DMC

• 2 other identifiers: BIO-2019-0447CA209-7DJ
• Study Type: interventional
• Target: 1
• Locations: 3 countries
• Sites: 4

Brief Summary

This is an Open-label, single-arm, multicenter Phase II pilot study to assess the efficacy and safety of BMS-936558 with stereotactic ablative radiation therapy after induction chemotherapy in cholangiocarcinoma.

Conditions

Cholangiocarcinoma

Keywords

cholangiocarcinoma; Immunotherapy; SBRT; PFS

Outcome Measures

Primary Outcomes (1)

• To evaluate the progression-free survival (PFS) at 8 months and the disease control rate (DCR) in patients with non-resectable locally-advanced or metastatic or recurrent intrahepatic or extrahepatic CCA following BMS-936558/SBRT treatment

  will be done at 8 months of the initial patient diagnosis and after 8 cycles of treatment

  8 months

Secondary Outcomes (4)

• To evaluate the overall survival (OS) rate in patients with advanced intrahepatic or extrahepatic CCA following BMS-936558/SBRT treatment.

  up to 2 years

• To evaluate tumor response rates at the primary and secondary sites using the response evaluation criteria in solid tumors (RECIST1.1) criteria.

  every 4 months from the date of first treatment visit until the date of first documented progression, assessed up to 2 years.

• To evaluate the duration of response at non-irradiated tumor sites in patients with Stage IV disease.

  every 4 months from the date of first treatment visit until the date of first documented progression, assessed up to 2 years.

• To evaluate the following biomarkers: CD3+, CD4+, and CD8+ , and changes in PD-L1 expression at baseline and following first cycle of BMS-936558and SBRT.

  at baseline/inclusion visit and Day20 (after radiotherapy)

Study Arms (1)

locally advanced, metastatic or recurrent cholangiocarcinoma

EXPERIMENTAL

D1: Compound: BMS-936558 treatment d8: radiotherapy D 20: CT guided Biopsy D 28: BMS-936558 treatment monthly: BMS-936558 treatment CT CAP: after 4doses

Drug: BMS-936558

Interventions

BMS-936558 DRUG

BMS-936558 followed by 30 grays of 3 to 5 fractions of high dose SBRT followed by monthly BMS-936558 until progression

Also known as: radiation therapy : SBRT

locally advanced, metastatic or recurrent cholangiocarcinoma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed and dated informed consent form.
• Patients aged ≥18 years.
• 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.
• Patients who have stable disease or partial response following 4 cycles of cisplatin/gemcitabine.
• ECOG performance score \<3
• o An estimated life expectancy of more than 3 months.
• Have adequate hematologic and biochemical function by meeting the following:
• Total bilirubin acceptable level ≤ 1.5 × the institutional upper limit of normal (ULN) range;
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) acceptable levels up to 5 x ULN range;
• Serum urea and serum creatinine acceptable levels up to 1.5 x ULN range;
• Calculated glomerular filtration rate ≥ 45 mL/min according to the Chronic Kidney Disease Epidemiology Collaboration equation (or local institutional standard method).
• Negative serum or urine pregnancy test at screening for women of childbearing potential who are sexually active.
• 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 BMS-936558 treatment administration, respectively.
• Candidate for percutaneous biopsy as per tumor location evidenced by CT scan and interventional radiologist.

You may not qualify if:

• Patients who have progression following 4 cycles of cisplatin/gemcitabine evidenced by CT scan as per RECIST 1.1.
• Active brain metastases or leptomeningeal metastases.
• Prior organ transplantation or allogenic stem-cell transplantation.
• 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).
• Active infection requiring systemic therapy within 28 days before the first dose of study treatment (e.g., urinary tract infection).
• Known history of testing positive for the human immunodeficiency virus or known acquired immunodeficiency syndrome.
• Evidence of liver cirrhosis.
• 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).
• Active autoimmune diseases that might deteriorate upon receiving an immune-stimulatory agent.
• Conditions such as vitiligo, psoriasis, diabetes type I, or hypo- or hyper-thyroid diseases not requiring immunosuppressive treatment are eligible.
• 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
• Hepatic insufficiency manifesting as clinical jaundice, hepatic encephalopathy, and/or variceal bleed within 60 days prior to study entry.

Sponsors & Collaborators

• American University of Beirut Medical Center: lead
• Bristol-Myers Squibb: collaborator

Study Sites (4)

Institut Jule Bordet

Brussels, 1000, Belgium

Location

Cliniques universitaires Saint-Luc

Brussels, 1200, Belgium

Location

American University of Beirut Medical Center

Beirut, Lebanon

Location

Centre hospitalier de Luxembourg

Luxembourg, Luxembourg

Location

Related Publications (1)

• Elias C, Zeidan YH, Bouferraa Y, Mukherji D, Temraz S, Charafeddine M, Al Darazi M, Shamseddine A. A phase II single arm study of Nivolumab with stereotactic Ablative radiation Therapy after induction chemotherapy in CHOlangiocarcinoma (NATCHO). BMC Cancer. 2022 Dec 12;22(1):1296. doi: 10.1186/s12885-022-10373-1.

  PMID: 36503610 DERIVED

MeSH Terms

Conditions

Cholangiocarcinoma

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Ali Shamseddine, MD

  American University of Beirut Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: single group assignment

Study Record Dates

• First Submitted: November 11, 2020
• First Posted: December 1, 2020
• Study Start: April 15, 2021
• Primary Completion: January 17, 2022
• Study Completion: January 17, 2022
• Last Updated: February 23, 2022

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

LU (1); LE (1); BE (2)