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Pembrolizumab Plus Lenvatinib In Second Line and Third Line Malignant Pleural mesotheLioma Patients (PEMMELA)

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ClinicalTrials.gov Identifier: NCT04287829
Recruitment Status : Recruiting
First Posted : February 27, 2020
Last Update Posted : March 3, 2021
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
The Netherlands Cancer Institute

Brief Summary:
There is no standard second line treatment in malignant pleural mesothelioma (MPM). Pembrolizumab has shown to be active in in small phase II studies in MPM. Its activity however, is limited, with a response rate up to 20%. So, there is a need for new treatment combinations with drugs that might exhibit a synergistic interaction with pembrolizumab.

Condition or disease Intervention/treatment Phase
Mesotheliomas Pleural Drug: Pembrolizumab Drug: Lenvatinib Phase 2

Detailed Description:
There is no standard second line treatment in malignant pleural mesothelioma (MPM). Pembrolizumab has shown to be active in in small phase II studies in MPM. Its activity however, is limited, with a response rate up to 20%. So, there is a need for new treatment combinations with drugs that might exhibit a synergistic interaction with pembrolizumab. The mechanisms of actions of lenvatinib, which has a broad spectrum of activities, predicts many synergistic interactions with PD-1 blocking. The aim of this study is to characterize the potential clinical activity, toxicity and biomarkers of outcome of pembrolizumab - lenvatinib in patients with recurrent MPM.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: PEMbrolizumab Plus Lenvatinib In Second Line And Third Line Malignant Pleural MEsotheLiomA Patients(PEMMELA)
Actual Study Start Date : March 1, 2021
Estimated Primary Completion Date : August 5, 2021
Estimated Study Completion Date : August 5, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Mesothelioma

Arm Intervention/treatment
Experimental: pembrolizumab and lenvatinib

Patients will receive pembrolizumab 200mg/iv (fixed dose) every 3 weeks and lenvatinib 20mg QD in a three weekly cycle.

Treatment continues until disease progression by modified (i)RECIST for MPM, severe toxicity, serious intercurrent illness, patient request for discontinuation, need or use for any other anti-cancer agent other than protocol treatment, except for palliative radiotherapy, for a maximum period of 35 cycles

Drug: Pembrolizumab
Infusion

Drug: Lenvatinib
Capsule




Primary Outcome Measures :
  1. Objective response rate defined by Modified (i)RECIST criteria for pleural mesothelioma [ Time Frame: Through study completion, an average of 1 year ]
    Complete response and partial response


Secondary Outcome Measures :
  1. Safety of pembrolizumab- lenvatinib [ Time Frame: Up to 90 days after last study drug intake ]
    Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

  2. Describe the disease control rate (DCR) at 3 and 6 months [ Time Frame: From date of registration until 6 months ]
    a percentage of the total number of patients in the study who are evaluable for the primary endpoint who have best overall response of CR or PR or SD.

  3. Objective response rate (ORR) [ Time Frame: Assessed up to 60 months ]
    Number of patients with a partial or complete response

  4. Progression-free survival [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months ]
    To describe PFS by independent radiological review


Other Outcome Measures:
  1. Immunological status [ Time Frame: before study and after 6 weeks of treatment ]
    The immunological status in the tumors before study and after 6 weeks of treatment with pembrolizumab +lenvatinib. This research will include PD-L1 status, mutational load and other potential biomarkers (e.g. micro vessel density count).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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:

  1. Histologically or cytologically diagnosed malignant pleural mesothelioma, age at least 18 years
  2. Progressive disease after at least 1 and maximal 2 prior systemic treatment lines, in which one of the lines contains a platinum-based doublet (both cisplatin and carboplatin are allowed) for unresectable MPM
  3. Measurable disease. At least one measurable lesion according to Modified (i)RECIST for pleural mesothelioma. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
  4. WHO-ECOG performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to date of allocation
  5. Adequate organ function
  6. Ability to understand the study and give signed informed consent (or legally acceptable representative if applicable) prior to beginning of protocol specific procedures including the approval of the thoracoscopy or transthoracic pleural biopsy before the first treatment cycle and an optional biopsy before the third treatment cycle
  7. No presence of clinically relevant treatment-related toxicity from previous chemotherapy, targeted therapy and/or radiotherapy. Note: Participates must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤2 neuropathy may be eligible
  8. No active uncontrolled infection, severe cardiac dysfunction (i.e. unstable angina, history of myocardial infarction within the past 12 months prior to screening, congestive heart failure > NYHA II, serious cardiac arrhythmia), unstable peptic ulcer, unstable diabetes mellitus or other seriously disabling condition
  9. Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 mmHg at screening ad no change in hypertensive medication within 1 week before the cycle 1/day1.
  10. No prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with another agent agents direct to another stimulatory or co-inhibitory T-cell receptor (eg CTLA-4, OC-40, CD137) or TKI or antibody targeting angiogenesis. Patients who have been treated with autologous tumor cell vaccination (eg. Dendritic cell-based immunotherapy) will be eligible
  11. No concomitant administration to any other experimental drugs under investigation ≤ 4 weeks prior to first admission of pembrolizumab- lenvatinib
  12. No prior radiotherapy within 2 weeks before start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids as therapy for radiation induced toxicities. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
  13. No major injuries and/or surgery within the past 4 weeks prior to first study dose with incomplete wound healing

Exclusion Criteria:

  1. presence of clinically relevant treatment-related toxicity from previous chemotherapy, targeted therapy and/or radiotherapy. Note: Participates must have recovered from all AEs due to previous therapies to 5Grade 1 or baseline. Participants with 52 neuropathy may be eligible
  2. active uncontrolled infection, severe cardiac dysfunction (i.e. unstable angina, history of myocardial infarction within the past 12 months prior to screening, congestive heart failure > NYHA II, serious cardiac arrhythmia), unstable peptic ulcer, unstable diabetes mellitus or other seriously disabling condition
  3. prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with another agent agents direct to another stimulatory or co-inhibitory T-cell receptor (eg CTLA-4, OC-40, CD137) or TKI or antibody targeting angiogenesis. Patients who have been treated with autologous tumor cell vaccination (eg. Dendritic cell-based imnnunotherapy) will be eligible
  4. concomitant administration to any other experimental drugs under investigation 5 4 weeks prior to first admission of pembrolizumab- lenvatinib

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): NCT04287829


Contacts
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Contact: S Burgers, PhD 0031205129111 s.burgers@nki.nl
Contact: D de Gooijer, MD 0031205129111 d.d.gooijer@nki.nl

Locations
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Netherlands
Antoni van Leeuwenhoekziekenhuis (NKI-AVL) Recruiting
Amsterdam, Noord-Holland, Netherlands, 1066 CX
Contact: S Burgers, Dr.    +31 (0)20-5122958    j.burgers@nki.nl   
Contact: W. A. Buikhuisen, MD    +31 (0)20-5122958    w.buikhuisen@nki.nl   
Principal Investigator: S Burgers, Dr.         
Sponsors and Collaborators
The Netherlands Cancer Institute
Merck Sharp & Dohme Corp.
Investigators
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Principal Investigator: S Burgers, PhD NKI-AvL
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Responsible Party: The Netherlands Cancer Institute
ClinicalTrials.gov Identifier: NCT04287829    
Other Study ID Numbers: N19PEM
First Posted: February 27, 2020    Key Record Dates
Last Update Posted: March 3, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Mesothelioma
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Mesothelial
Pembrolizumab
Lenvatinib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action