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Pembrolizumab and GM-CSF in Biliary Cancer

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ClinicalTrials.gov Identifier: NCT02703714
Recruitment Status : Recruiting
First Posted : March 9, 2016
Last Update Posted : April 27, 2018
Sponsor:
Information provided by (Responsible Party):
Robin Kate Kelley, University of California, San Francisco

Brief 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 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.


Condition or disease Intervention/treatment Phase
Biliary Cancer Drug: Pembrolizumab Drug: Sargramostim Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 42 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Trial of Pembrolizumab (MK-3475) With GM-CSF Induction in Advanced Biliary Cancers
Actual Study Start Date : April 27, 2016
Estimated Primary Completion Date : March 2019
Estimated Study Completion Date : March 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Treatment
Patients receive pembrolizumab IV over 30 minutes on day 1. Patients also receive sargramostim 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.
Drug: Pembrolizumab
200 mg given IV
Other Name: MK-3475

Drug: Sargramostim
250 µg given SC
Other Name: GM-CSF




Primary Outcome Measures :
  1. Overall response rate (ORR) [ Time Frame: Response will be assessed from start of treatment through date of discontinuation for up to 2 years ]
    Proportion of subjects with Response Evaluation Criteria in Solid Tumors (RECIST) 1.1-measurable disease at study entry who have a complete response (CR) or partial response (PR) (confirmed + unconfirmed) using RECIST 1.1 at any time during the main study


Secondary Outcome Measures :
  1. Incidence of adverse events graded using Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: 2. During study treatment and for 30 days after last dose or until start of new treatment (for up to 2 years) ]
    Safety events will be summarized based on frequency and proportion of total subjects, by system organ class and preferred term. Separate summaries with descriptive statistics will be presented according to anatomic subtype of biliary cancer (e.g. intrahepatic, hilar/perihilar, extrahepatic, gallbladder cancer [GBC]). In overall cohort only related >/=grade 3 AEs .

  2. PD-L1 positive status [ Time Frame: Pre-treatment archival tumor tissue and any tumor tissue sampling required for standard of care during treatment or within 2 years after treatment ]
    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)

  3. Progression free-survival [ Time Frame: Within 4 years after start of study treatment ]
    Time from date of first dose of protocol therapy to date of first documented radiographic and/or clinical disease progression or death from any cause

  4. Duration of response [ Time Frame: Within 4 years after start of study treatment ]
    Time from first documented evidence of CR or PR until the first documented sign of disease progression or death

  5. Overall survival [ Time Frame: Within 4 years after start of treatment ]
    Time from first dose of protocol therapy to the date of death due to any cause



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Be willing and able to provide written informed consent for the trial.
  • Have a performance status of 0 or 1 on the ECOG Performance Scale.
  • Demonstrate adequate organ function

    • Absolute neutrophil count (ANC) >= 1,000/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)
    • 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 or C virus (HBV or 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

Exclusion Criteria:

  • 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 TB (Bacillus Tuberculosis).
  • 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.

    • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02703714


Contacts
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Contact: R. Kate Kelley, M.D. 877-827-3222 cancertrials@ucsf.edu

Locations
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United States, California
UCSF Helen Diller Family Comprehensive Cancer Center Recruiting
San Francisco, California, United States, 94158
Contact: Lesley McCarthy, RN    415-514-5830    Lesley.Mccarthy@ucsf.edu   
Sponsors and Collaborators
Robin Kate Kelley
Investigators
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Principal Investigator: R. Kate Kelley, M.D. University of California, San Francisco

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Responsible Party: Robin Kate Kelley, Associate Professor, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT02703714     History of Changes
Other Study ID Numbers: 154524
NCI-2017-01372 ( Other Identifier: NCI )
First Posted: March 9, 2016    Key Record Dates
Last Update Posted: April 27, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by Robin Kate Kelley, University of California, San Francisco:
Advanced
Locally-advanced
Not eligible for resection
Prior chemotherapy treatment
Additional relevant MeSH terms:
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Biliary Tract Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Biliary Tract Diseases
Digestive System Diseases
Pembrolizumab
Sargramostim
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs