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A Study of Pembrolizumab in Patients With Neuroendocrine Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02939651
Recruitment Status : Active, not recruiting
First Posted : October 20, 2016
Last Update Posted : June 5, 2020
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Fox Chase Cancer Center

Tracking Information
First Submitted Date  ICMJE October 3, 2016
First Posted Date  ICMJE October 20, 2016
Last Update Posted Date June 5, 2020
Actual Study Start Date  ICMJE October 26, 2016
Estimated Primary Completion Date September 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 18, 2016)
Objective Response Rate (ORR) [ Time Frame: Upto 3 years ]
To estimate objective response rate (ORR), using RECIST 1.1, in previously treated metastatic High Grade Neuroendocrine Tumors (HGNET) patients treated with pembrolizumab monotherapy
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 18, 2016)
  • Progression free survival (PFS) [ Time Frame: Upto 3 years ]
    To evaluate progression free survival (PFS) (using RECIST 1.1) in metastatic HGNET patients treated with pembrolizumab monotherapy.
  • Overall Survival [ Time Frame: Upto 3 years ]
    To evaluate overall survival (OS) in metastatic HGNET patients treated with pembrolizumab monotherapy.
  • Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0 [ Time Frame: Upto 3 years ]
    Incidence of toxicity, graded according to National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.0.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: October 18, 2016)
  • PD-1 expression on tumor samples pre-treatment [ Time Frame: 6 weeks ]
    Baseline, at week 6 and at progression
  • PD-1 expression and leukocyte activation markers on circulating lymphocytes [ Time Frame: Week 6 ]
    baseline, at week 6, and end of treatment
  • Functional responses (degranulation) by NK cells [ Time Frame: Week 6 ]
    Baseline, at week 6, and end of treatment
Original Other Pre-specified Outcome Measures Same as current
Descriptive Information
Brief Title  ICMJE A Study of Pembrolizumab in Patients With Neuroendocrine Tumors
Official Title  ICMJE A Phase 2, Open-label Study of Pembrolizumab Monotherapy in Patients With Metastatic High Grade Neuroendocrine Tumors
Brief Summary The purpose of this research study is to test if pembrolizumab is safe and effective for treating patients with metastatic high-grade neuroendocrine tumors who have failed platinum based chemotherapy.The study drug, pembrolizumab has been FDA approved for treating a type of skin cancer called melanoma and for metastatic non-small cell lung cancer. However, it is not approved for treatment of metastatic high-grade neuroendocrine tumors.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Neuroendocrine Tumors
Intervention  ICMJE Drug: Pembrolizumab
Pembrolizumab given intravenously at a fixed dose of 200mg every 3 weeks
Other Names:
  • Keytruda
  • MK-3475
Study Arms  ICMJE Experimental: Pembrolizumab
Monotherapy with PD-1 antibody pembrolizumab
Intervention: Drug: Pembrolizumab
Publications * Vijayvergia N, Dasari A, Deng M, Litwin S, Al-Toubah T, Alpaugh RK, Dotan E, Hall MJ, Ross NM, Runyen MM, Denlinger CS, Halperin DM, Cohen SJ, Engstrom PF, Strosberg JR. Pembrolizumab monotherapy in patients with previously treated metastatic high-grade neuroendocrine neoplasms: joint analysis of two prospective, non-randomised trials. Br J Cancer. 2020 Apr;122(9):1309-1314. doi: 10.1038/s41416-020-0775-0. Epub 2020 Mar 10.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: October 18, 2016)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2020
Estimated Primary Completion Date September 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Patients must have histologically or cytologically confirmed metastatic, high grade NET (Ki67 >20%), excluding any high grade NETs of large or small cell type of lung/thymus origin and merkel cell carcinoma
  2. Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension in accordance with RECIST criteria v. 1.1 as described in detail in section 12.0
  3. Has received prior therapy with at least 1 platinum-containing regimen
  4. Age > 18 years.
  5. ECOG performance status 0 or 1
  6. Patients must have normal organ and marrow function
  7. Female participants of childbearing potential must have a negative serum pregnancy within 72 hours prior to receiving the first dose of study medication). They should also 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. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
  8. Male participants must 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 Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
  9. Ability to understand and willingness to sign a written informed consent and HIPAA consent document

Exclusion Criteria:

  1. 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. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
  2. Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
  3. Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
  4. Prior anti-cancer therapy with a monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or not recovered from adverse events (improved to grade 1 or less) due to mAbs administered more than 4 weeks earlier.
  5. Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks (12 weeks for measurable sites of CNS disease) prior to study Day 1 or not recovered from adverse events (improved to grade 1 or less) due to a previously administered agent. Note: Subjects with neuropathy or ≤ Grade 2 alopecia are an exception to this criterion and may qualify for the study. Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
  6. Known additional malignancy that is progressing or requires active treatment except superficial malignancies of the skin and in situ cervical cancer
  7. Has an 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.
  8. Has history of (non-infectious) pneumonitis that required steroids, evidence of interstitial lung disease or active non-infectious pneumonitis.
  9. Active infection requiring systemic therapy at enrollment.
  10. Has a known history of active TB (Bacillus Tuberculosis)
  11. Hypersensitivity to pembrolizumab or any of its excipients
  12. Has received a live virus vaccine within 30 days of planned start of trial treatment.
  13. Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening period through 120 days after the last dose of trial treatment
  14. Prior therapy with an anti-programmed cell death 1 (PD-1), anti-programmed cell death 1 ligand (PDL-1), anti-PD-L2, or with an agent directed to another co-inhibitory T-cell receptor (e.g. CTLA-4, OX-40, CD137)
  15. Known history of human immunodeficiency virus (HIV)
  16. Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative]).
  17. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  18. 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT02939651
Other Study ID Numbers  ICMJE GI-087
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Fox Chase Cancer Center
Study Sponsor  ICMJE Fox Chase Cancer Center
Collaborators  ICMJE Merck Sharp & Dohme Corp.
Investigators  ICMJE
Principal Investigator: Namrata Vijayvergia, MD Fox Chase Cancer Center
PRS Account Fox Chase Cancer Center
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP