Clinical Trial 19207

Cancer Type: Gastrointestinal Tumor
Interventions:Pembrolizumab (Keytruda)

Study Type: Treatment
Phase of Study: Phase II
Investigators:

  • Jonathan Strosberg

Overview

Study Title

Phase II Study of Pembrolizumab in Advanced Poorly-Differentiated and/or High-Grade Neuroendocrine Tumors/Carcinomas

Summary

The purpose of this study is to: Assess overall radiographic response rate (ORR); Assess progression-free survival (PFS); Test the safety and tolerability of Pembrolizumab.

Objective

Objective: To assess the overall radiographic response rate (ORR) associated with pembrolizumab in patients with advanced, progressive high-grade and/or poorly differentiated extrapulmonary neuroendocrine cancers. Objective: To assess progression-free survival (PFS) in this population based on RECIST 1.1 and irRECIST. Objective: To assess duration of response (DOR) by RECIST 1.1. Objective: To assess overall survival (OS) in this population. Objective: To assess safety and tolerability.

Inclusion Criteria

  • Diagnosis/Condition for entry into the trial: Metastatic poorly differentiated and/or high-grade neuroendocrine tumor/carcinoma originating outside of the lung (including unknown primary)
  • Evidence of radiographic disease progression with scan documenting progression occurring within 8 weeks of signing informed consent
  • At least one prior line of systemic treatment. If the only prior line of treatment was adjuvant or neoadjuvant, patient must have completed treatment within 12 months. There is no limit to number of prior therapies.
  • Willing and able to provide written informed consent/assent for the trial.
  • Less than or equal to 18 years of age on day of signing informed consent.
  • Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
  • Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
  • Demonstrate adequate organ function and laboratory values. All screening labs should be performed within 10 days of treatment initiation.
  • Females of childbearing potential (FOCBP) should have a negative serum pregnancy within 72 hours prior to receiving the first dose of study medication.
  • FOCBP must agree to use adequate contraception as outlined in study documentation for the course of the through 120 days after the last dose of study medication.
  • Male participants of childbearing potential must agree to use an adequate method of contraception as outlined in study documentation, starting with the first dose of study therapy through 120 days after the last dose of study therapy.

  • Exclusion Criteria

  • 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.
  • A diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
  • Known history of active TB (Bacillus Tuberculosis)
  • Hypersensitivity to pembrolizumab or any of its excipients.
  • Has had a prior 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 had prior chemotherapy, targeted small molecule therapy, or radiation therapy 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. - Note: Potential participants with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study. Note: If have received major surgery, must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
  • 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.
  • Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Potential participants 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.
  • Has active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy is not considered a form of systemic treatment.
  • History of (non-infectious) pneumonitis that required steroids, or current pneumonitis.
  • An active infection requiring systemic therapy.
  • History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with participation for the full duration of the trial, or is not in the best interest of the potential participant.
  • Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • 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.
  • Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  • Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  • Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.