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Biliary CancerPhase 2NCT02703714

Pembrolizumab and GM-CSF in Biliary Cancer

A Phase 2 study testing Pembrolizumab and Sargramostim in people with Biliary Cancer, run by Robin Kate Kelley at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is an open label phase II trial to examine efficacy and safety of a novel combination of pembrolizumab plus induction GM-CSF in patients with advanced biliary cancers treated at University of California, San Francisco (UCSF). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Biliary Cancer
What is being tested?
Pembrolizumab and Sargramostim
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
42 participants
Where
1 siteUnited States
Study dates
6 May 2016to 31 Dec 2020
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Be willing and able to provide written informed consent for the trial.
  • Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
  • Demonstrate adequate organ function
  • Absolute neutrophil count (ANC) >= 1,000/microliter (mcL)(performed within 28 days of treatment initiation)
  • Platelets >= 60,000/mcL (>= 75,000/mcL in expansion cohort) (performed within 28 days of treatment initiation)
  • Hemoglobin >= 9 g/dL or >= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment) (performed within 28 days of treatment initiation)
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  • Serum creatinine =< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate (GFR) can also be used in place of creatinine or creatinine clearance (CrCl)) >= 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN (performed within 28 days of treatment initiation)
  • Serum total bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN (performed within 28 days of treatment initiation)
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase (SGOT)) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase (SGPT)) =< 5 X ULN (performed within 28 days of treatment initiation)
  • Albumin >= 2.5 mg/dL (performed within 28 days of treatment initiation)
  • International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as prothrombin time (PT) or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (performed within 28 days of treatment initiation)
  • Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants (performed within 28 days of treatment initiation)
  • Patients with known hepatitis B (HBV) or hepatitis C virus (HCV) infection are eligible provided liver function parameters meet laboratory eligibility criteria
  • Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication
  • Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
  • ADDITIONAL EXPANSION COHORT SUBJECT INCLUSION CRITERIA
  • Tumor measurable by RECIST 1.1 including >= 1 target lesion not planned for biopsy
  • Presence of >= 1 tumor lesion not included as a RECIST 1.1 target lesion which is assessed by investigator and/or radiologist as likely to be amenable to percutaneous biopsy by punch, computed tomography (CT)-, or ultrasound-guided core needle biopsy for serial sampling on treatment
  • Platelet count >= 75,000/mcL
  • No contraindication to tumor biopsy at time of study enrollment
  • Consent for on-treatment paired biopsies

Who cannot join

  • Is currently participating and receiving study therapy or has participated and received study therapy in a study of an investigational agent, or used an investigational device within 4 weeks of the first dose of treatment.
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy for purposes of immunosuppression or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
  • Has a known history of active Bacillus Tuberculosis (TB).
  • Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  • Has untreated active Hepatitis B (e.g., HBsAg reactive).
  • Has an active infection requiring systemic antibiotic therapy at time of enrollment.
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  • Treatment with antibiotic prophylaxis for indwelling biliary stent(s) or peri-procedural antibiotics for uncomplicated biliary stent exchanges is allowed and not an exclusion
  • Hypersensitivity to pembrolizumab or any of its excipients.
  • Has received treatment with an anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
  • Has received treatment with chemotherapy, targeted small molecule therapy, or radiation therapy to non-liver sites within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent administered more than 2 weeks earlier.
  • Has had prior chemoembolization, bland embolization, radioembolization, local ablative therapies, radiation to liver tumors, or major surgery such as liver resection within 4 weeks prior to study enrollment or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to intervention more than 4 weeks earlier.
  • Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment.
  • Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • Has known history of or any evidence of active, non-infectious pneumonitis.
  • Has had prior liver or other organ transplantation.
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
  • Has received a live vaccine within 30 days of planned start of study therapy.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of California San Francisco

    San Francisco, California, 94158

Other trials in United States

About this study

Official title: Phase II Trial of Pembrolizumab (MK-3475) With GM-CSF Induction in Advanced Biliary Cancers

This is an open label phase II trial to examine efficacy and safety of a novel combination of pembrolizumab plus induction GM-CSF in patients with advanced biliary cancers treated at University of California, San Francisco (UCSF).

This phase II study will examine the efficacy and safety of the novel combination of pembrolizumab plus induction GM-CSF in advanced biliary cancer patients with the hypotheses that the combination may increase proportion of patients with overall response compared to contemporary historical controls, with acceptable safety.

Conditions
Biliary Cancer
Keywords
Advanced, Locally-advanced, Not eligible for resection, Prior chemotherapy treatment
Medical subject headings
Biliary Tract Neoplasms

What participants receive

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

  • PembrolizumabDrug

    Also called MK-3475, Keytruda

    200 mg given intravenously (IV)

  • SargramostimDrug

    Also called GM-CSF

    250 µg given subcutaneously (SC)

Study groups in NCT02703714
Study groupRoleWhat they receive
Pembrolizumab and GM-CSFExperimentalPatients receive pembrolizumab IV over 30 minutes on day 1. Patients also receive sargramostim subcutaneous injection (SC) on days 1-14 of courses 1-2 or 2-3. Treatment repeats every 21 days for up to 2 courses for sargramostim and for up to 35 courses (24 months) for pembrolizumab in the absence of disease or unaccepted toxicity.
Receives: Drug: Pembrolizumab; Drug: Sargramostim

What is being measured

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

  1. Overall Response Rate (ORR)

    Proportion of subjects with measurable disease at study entry who obtained either a complete response (CR) or partial response (PR) (confirmed + unconfirmed) using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 at any time during the course of treatment.

    Measured: Up to 2 years

Secondary outcomes (9)

  1. Proportion of Participants With Treatment-related AEs

    Safety events will be summarized based on proportion of total subjects, by preferred term. Only treatment-related >=grade 3 Adverse Events (AE)s will be reported.

    Measured: During study treatment and for 30 days after last dose or until start of new treatment (up to 2 years)

  2. Proportion of Participants With PD-L1 Positive Status

    PD-L1 expression will be measured by immunohistochemistry (IHC) and classified as positive or negative by central laboratory testing (QualTek Laboratories) using pre-specified cut-points; will be reported along with 95% confidence interval (CI)

    Measured: Up to 4 years

  3. Proportion of Participants With Progression-Free Survival (PFS) at 6 Months

    Proportion of participants with PFS Time from date of first dose of protocol therapy to date of first documented radiographic and/or clinical disease progression per RECIST version 1.1 or death from any cause

    Measured: 6 months after start of study treatment

  4. Median Duration of Response

    Time from first documented evidence of CR or PR until the first documented sign of disease progression or death

    Measured: Within 4 years after start of study treatment

  5. Median Duration of Response Stratified by Sub-type of Biliary Cancer

    Time from first documented evidence of CR or PR until the first documented sign of disease progression or death stratified by sub-type of biliary cancer

    Measured: Within 4 years after start of study treatment

  6. Median Progression Free-Survival (PFS)

    Time from date of first dose of protocol therapy to date of first documented radiographic and/or clinical disease progression per RECIST version 1.1 or death from any cause

    Measured: Within 4 years after start of study treatment

  7. Median PFS Stratified by Sub-type of Biliary Cancer

    Time from date of first dose of protocol therapy to date of first documented radiographic and/or clinical disease progression per RECIST version 1.1 or death from any cause stratified by sub-type of biliary cancer

    Measured: Within 4 years after start of study treatment

  8. Median Overall Survival (OS)

    Time from first dose of protocol therapy to the date of death due to any cause

    Measured: Within 4 years after start of treatment

  9. Median Overall Survival (OS) Stratified by Sub-type of Biliary Cancer

    Time from first dose of protocol therapy to the date of death due to any cause stratified by sub-type of biliary cancer.

    Measured: Within 4 years after start of treatment

Timeline

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

  1. First posted9 Mar 2016 (estimated)
  2. Study start6 May 2016
  3. Primary completion31 Dec 2020
  4. Study completion31 Dec 2020

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
Masking
None (open label)
Enrolment
42 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02703714
Sponsor's protocol ID
154524
Other IDs
NCI-2017-01372, R03CA212877
Status last verified
Jan 2022
First submitted
4 Mar 2016
Last updated
25 Jan 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Keenan BP, McCarthy EE, Ilano A, Yang H, Zhang L, Allaire K, Fan Z, Li T, Lee DS, Sun Y, Cheung A, Luong D, Chang H, Chen B, Marquez J, Sheldon B, Kelley RK, Ye CJ, Fong L. Circulating monocytes associated with anti-PD-1 resistance in human biliary cancer induce T cell paralysis. Cell Rep. 2022 Sep 20;40(12):111384. doi: 10.1016/j.celrep.2022.111384.

    PubMed 36130508

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pembrolizumab and Sargramostim in people with Biliary Cancer, run by Robin Kate Kelley at 1 site in United States.

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 21 inclusion and 21 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: finished, as of the sponsor's last update on 25 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. 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?

Yes. Results are posted in the registry (first posted 12 Jan 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Overall Response Rate (ORR) (time frame: Up to 2 years). 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 NCT02703714, 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 25 Jan 2022.

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