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Phase II Study of Pembrolizumab and Lenvatinib in Advanced Well-differentiated Neuroendocrine Tumors

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ClinicalTrials.gov Identifier: NCT03290079
Recruitment Status : Recruiting
First Posted : September 21, 2017
Last Update Posted : July 14, 2021
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute

Tracking Information
First Submitted Date  ICMJE September 19, 2017
First Posted Date  ICMJE September 21, 2017
Last Update Posted Date July 14, 2021
Actual Study Start Date  ICMJE December 15, 2017
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 19, 2017)
Objective Radiographic Response Rate (ORR) [ Time Frame: Up to 12 months ]
Response Evaluation Criteria in Solid Tumors (RECIST) based response rate. Complete Response (CR): Disappearance of all extranodal target lesions. All pathological lymph nodes must have decreased to <10 mm in short axis. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (SLD) of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): SLD increased by at least 20% from the smallest value on study (including baseline, if that is the smallest). The SLD must also demonstrate an absolute increase of at least 5mm. (Two lesions increasing from 2 mm to 3 mm, for example, does not qualify). Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 19, 2017)
  • Duration of Response (DOR) [ Time Frame: Up to 12 months ]
    DOR, defined as the time from first documented evidence of Complete Response (CR) or Partial Response (PR) until disease progression or death due to any cause, whichever occurs first.
  • Progression Free Survival (PFS) [ Time Frame: Up to 12 months ]
    PFS, defined as the time from initial treatment to the first documented disease progression according to RECIST 1.1, or death due to any cause, whichever occurs first.
  • Overall Survival (OS) [ Time Frame: Up to 12 months ]
    OS defined as the time from initial treatment until death from any cause.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase II Study of Pembrolizumab and Lenvatinib in Advanced Well-differentiated Neuroendocrine Tumors
Official Title  ICMJE Phase II Study of Pembrolizumab and Lenvatinib in Advanced Well-differentiated Neuroendocrine Tumors
Brief 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 in combination with lenvatinib
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
Simon 2-stage design
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Neuroendocrine Tumors
  • Neuroendocrine Carcinoma
  • Neuroendocrine Cancer
Intervention  ICMJE
  • Drug: Pembrolizumab
    200 mg Pembrolizumab by IV on Day 1 of each 3 week cycle.
    Other Name: Keytruda®
  • Drug: Lenvatinib
    20 mg Lenvatinib by mouth every day of each 3 week cycle
    Other Name: Lenvima®
Study Arms  ICMJE Experimental: Pembrolizumab & Lenvatinib treatment
Pembrolizumab 200 mg will be administered as a 30 minute intravenous (IV) infusion every 3 weeks, in addition to 20 mg Lenvatinib by mouth every day of each 3 week cycle. Estimated average length of treatment per participant: 4 months.
Interventions:
  • Drug: Pembrolizumab
  • Drug: Lenvatinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 15, 2021)
35
Original Estimated Enrollment  ICMJE
 (submitted: September 19, 2017)
30
Estimated Study Completion Date  ICMJE December 2023
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Diagnosis/Condition for entry into the trial: Metastatic well differentiated neuroendocrine tumors of primary lung, thymic, small bowel and colorectal origin (including unknown primary)
  • Evidence of radiographic disease progression with scan documenting progression occurring within 8 months of signing informed consent
  • At least two prior lines 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.
  • ≥ 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 14 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:

  • Poorly differentiated neuroendocrine carcinoma
  • Pancreatic neuroendocrine tumor
  • 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 within 3 weeks, must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. Adequate wound healing after major surgery must be assessed clinically, independent of time elapsed for eligibility.
  • Serious non-healing wound, ulcer or bone fracture
  • Has pre-existing >/= Grade 3 gastrointestinal (GI) or non-GI fistula
  • Has significant cardiovascular impairment within 12 months of the first dose of study drug
  • 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 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.
  • 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.
  • Has received prior therapy with a tyrosine kinase inhibitor (TKI) (e.g.; sunitinib, pazopanib, cabozantinib)
  • 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.
  • Uncontrolled hypertension defined as systolic blood pressure >150 mmHg or diastolic pressure >90 mmHg, despite optimal medical management
  • Thrombotic or embolic events such as a cerebrovascular accident including transient ischemic, attacks, DVT within the past 6 months
  • Bleeding or thrombotic disorders or use of anticoagulants, such as warfarin, or similar agents requiring therapeutic international normalized ration (INR) monitoring.(Treatment with low molecular weight heparin (LMWH) is allowed)
  • Marked baseline prolongation of QT/QTc interval (QTc interval ≥ 480 msec) using the Fridericia method (QTc = QT/RR0.33) for QTc analysis
  • Clinically significant bleeding within 4 weeks
  • Medical need for the continued use of potent inhibitors/inducers of CYP3A4
  • Creatinine clearance <30 mL/min
  • Any condition that impairs patient's ability to swallow whole pills or gastrointestinal malabsorption that, in the investigator's opinion, might affect absorption of lenvatinib
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03290079
Other Study ID Numbers  ICMJE MCC-19207
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party H. Lee Moffitt Cancer Center and Research Institute
Study Sponsor  ICMJE H. Lee Moffitt Cancer Center and Research Institute
Collaborators  ICMJE Merck Sharp & Dohme Corp.
Investigators  ICMJE
Principal Investigator: Jonathan Strosberg, M.D. H. Lee Moffitt Cancer Center and Research Institute
PRS Account H. Lee Moffitt Cancer Center and Research Institute
Verification Date July 2021

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