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CholangiocarcinomaPhase 2NCT04648319

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

A Phase 2 study testing BMS-936558 in people with Cholangiocarcinoma, run by American University of Beirut Medical Center at 4 sites in 3 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Cholangiocarcinoma
What is being tested?
BMS-936558
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1 participants
Where
4 sitesin 3 countries
Study dates
15 Apr 2021to 17 Jan 2022
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.
  • Transmural myocardial infarction within 6 months of enrollment; provided that anti-platelets cannot be stopped to perform percutaneous biopsy.
  • 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.
  • Serious cardiac arrhythmia requiring medical treatment provided that anti-platelets cannot be stopped to perform percutaneous biopsy.
  • Recent cerebral vascular accident/stroke within 6 months of enrollment provided that anti-platelets cannot be stopped to perform percutaneous biopsy.
  • End-stage renal disease requiring dialysis.
  • 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.
  • Vaccination within 4 weeks of the first dose of BMS-936558 and while on trial is prohibited except for administration of inactivated vaccines.
  • Treatment with an investigational agent within 28 days before the first dose of study treatment.
  • 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 co-stimulation or checkpoint pathways.
  • Patients suspected by the physician that he/she will not be compliant to the protocol conduct.
  • Pregnant women are excluded from this study; breastfeeding should be discontinued.
  • Patients participating in another clinical trial.
  • Patients not willing to sign the consent form.
  • Any psychiatric condition that would prohibit the understanding or rendering of informed consent.
  • Legal incapacity or limited legal capacity patients receiving other oncology specific medication not authorized in the protocol.

Trial locations and contacts

4 sites in 3 countries.

4 sites in 3 countries

Belgium2 sites

  • Institut Jule Bordet

    Brussels, 1000

  • Cliniques universitaires Saint-Luc

    Brussels, 1200

Other trials in Belgium

Lebanon1 site

  • American University of Beirut Medical Center

    Beirut

Other trials in Lebanon

Luxembourg1 site

  • Centre hospitalier de Luxembourg

    Luxembourg

Other trials in Luxembourg

About this study

Official title: A Pilot Study of BMS-936558 With Stereotactic Ablative Radiation Therapy After Induction Chemotherapy in Cholangiocarcinoma

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.

Read the detailed description

The current standard regimen for advanced biliary tract cancers as per NCCN guidelines (version 2.2019) is gemcitabine plus cisplatin. However, since no single chemotherapy agent or combination regimen has consistently led to durable tumor regression, prevention of recurrent obstruction following palliative intervention, and extension of survival beyond 8 to 15 months, there is a pressing need for new treatment approaches in patients with dismal prognosis. Recent discoveries in tumor immunology, paralleled by technological advances in radiation therapy, have provided promising role for combining ablative radiotherapy with targeted immune modulators (El Chediak et al., 2017).

objectives: Primary: 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 cholangiocarcinoma (CCA) following BMS-936558 /stereotactic ablative radiation therapy (SBRT) treatment.

Secondary:

  1. To evaluate the overall survival (OS) rate in patients with advanced intrahepatic or extrahepatic CCA following BMS-936558/SBRT treatment. .
  2. To evaluate tumor response rates at the primary and secondary sites using the response evaluation criteria in solid tumors (RECIST1.1) criteria.
  3. To evaluate the duration of response at non-irradiated tumor sites in patients with Stage IV disease.
  4. To evaluate the following biomarkers: CD3+, CD4+, and CD8+ T cell infiltration, and changes in PD-L1 expression at baseline and following first cycle of BMS-936558 and SBRT.
  5. To assess the safety and tolerability of BMS-936558/SBRT according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAEv5).
  6. To assess the quality of life of the patients through completed FACT-Hep questionnaires.
Being tested
BMS-936558
Keywords
cholangiocarcinoma, Immunotherapy, SBRT, PFS
Medical subject headings
Cholangiocarcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BMS-936558Drug

    Also called radiation therapy : SBRT

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

Study groups in NCT04648319
Study groupRoleWhat they receive
locally advanced, metastatic or recurrent cholangiocarcinomaExperimentalD1: Compound: BMS-936558 treatment d8: radiotherapy D 20: CT guided Biopsy D 28: BMS-936558 treatment monthly: BMS-936558 treatment CT CAP: after 4doses
Receives: Drug: BMS-936558

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 8 months

Secondary outcomes (4)

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

    survival status will be evaluated every 3 months after progression

    Measured: up to 2 years

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

    evaluation will be done by CT scan of chest ,abdomen and pelvis every 4 months from the D1 ( after each 4 cycles of treatment until progression )

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

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

    evaluation will be done by CT scan of abdomen, pelvis and chest every 4 months (after every 4 cycles of treatment until progression )

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

  4. 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.

    biomarkers will be assessed from baseline biopsy and after receiving first BMS-936558and SBRT for changes.

    CD3+, CD4+, and CD8+: Will be quantified in mm2 in the most abundant tumor-infiltrating area in both, the stroma and the tumor, of the baseline biopsy (continuous variable) PD-L1: Will be evaluated on tumor cells and infiltrating immune T cells and be classified as negative or positive or not applicable (categorical variable)

    Measured: at baseline/inclusion visit and Day20 (after radiotherapy)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Dec 2020
  2. Study start15 Apr 2021
  3. Primary completion17 Jan 2022
  4. Study completion17 Jan 2022

Why it stopped: pharma company decision to withdraw the financial and IMP support

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
single group assignment
Masking
None (open label)
Enrolment
1 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04648319
Sponsor's protocol ID
BIO-2019-0447
Other IDs
CA209-7DJ
Status last verified
Nov 2020
First submitted
11 Nov 2020
Last updated
23 Feb 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 36503610

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing BMS-936558 in people with Cholangiocarcinoma, run by American University of Beirut Medical Center at 4 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 23 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Belgium, Lebanon, Luxembourg. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: pharma company decision to withdraw the financial and IMP support). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: 8 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04648319, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Feb 2022.

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