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 : January 17, 2023
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Mesotheliomas Pleural | Drug: Pembrolizumab Drug: Lenvatinib | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 58 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 : | December 5, 2024 |
Estimated Study Completion Date : | December 5, 2024 |
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 RECIST 1.1 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 |
- Objective response rate defined by Modified RECIST 1.1 criteria for pleural mesothelioma [ Time Frame: Through study completion, an average of 1 year ]Complete response and partial response
- 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
- 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.
- Objective response rate (ORR) [ Time Frame: Assessed up to 60 months ]Number of patients with a partial or complete response
- 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
- 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).
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.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Histologically or cytologically diagnosed malignant pleural mesothelioma, age at least 18 years
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Progressive disease after at least 1 and maximal 2 prior systemic treatment lines:
- Cohort 1: patients, in which one of the lines contains a platinum-based doublet (both cisplatin and carboplatin are allowed) for unresectable MPM (CLOSED)
- Cohort 2: patients with only in which one of the lines contains nivolumab-ipilimumab immunotherapy as first line treatment for unresectable MPM. No prior chemotherapy.
- Measurable disease. At least one measurable lesion according to Modified RECIST 1.1 for pleural mesothelioma. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
- WHO-ECOG performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to date of allocation
- Adequate organ function
- 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
- 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
- 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
- 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.
- 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 in the first cohort. Patients who have been treated with autologous tumor cell vaccination (eg. Dendritic cell-based immunotherapy) will be eligible in the first cohort. (First cohort is closed).
- No concomitant administration to any other experimental drugs under investigation ≤ 4 weeks prior to first admission of pembrolizumab- lenvatinib
- 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.
- No major injuries and/or surgery within the past 4 weeks prior to first study dose with incomplete wound healing
Exclusion Criteria:
- 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
- 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
- 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 in the first cohort. Patients who have been treated with autologous tumor cell vaccination (eg. Dendritic cell-based imnnunotherapy) will be eligible in the first cohort. (CLOSED)
- concomitant administration to any other experimental drugs under investigation 5 4 weeks prior to first admission of pembrolizumab- lenvatinib
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
Contact: S Burgers, PhD | 0031205129111 | s.burgers@nki.nl | |
Contact: L Douma, MD | 0031205129111 | l.douma@nki.nl |
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. |
Principal Investigator: | S Burgers, PhD | NKI-AvL |
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: | January 17, 2023 |
Last Verified: | September 2022 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Undecided |
Studies a U.S. FDA-regulated Drug Product: | No |
Studies a U.S. FDA-regulated Device Product: | No |
Mesothelioma Mesothelioma, Malignant Adenoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Neoplasms, Mesothelial Lung Neoplasms Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site |
Pleural Neoplasms Lung Diseases Respiratory Tract Diseases Pembrolizumab Lenvatinib Antineoplastic Agents, Immunological Antineoplastic Agents Immune Checkpoint Inhibitors Molecular Mechanisms of Pharmacological Action Protein Kinase Inhibitors Enzyme Inhibitors |