First-line Pembrolizumab Plus Platinum Doublet Chemotherapy With Lenvatinib in Unresectable Malignant Pleural Mesothelioma：Multi-Institutional, Single-Arm Phase 2 Trial
Overview
- Phase
- Phase 2
- Intervention
- Lenvatinib
- Conditions
- Malignant Pleural Mesothelioma
- Sponsor
- Hyogo Medical University
- Enrollment
- 25
- Locations
- 1
- Primary Endpoint
- Tumor shrinkage (response rate) (Physician Judgment by Medical Institution, Modified RECIST [Response Evaluation Criteria in Solid Tumors] criteria)
- Status
- Recruiting
- Last Updated
- 11 months ago
Overview
Brief Summary
In this Phase-II study, the investigators will investigate the efficacy and safety of lenvatinib in combination with pembrolizumab and chemotherapy in patients with malignant pleural mesothelioma.
Detailed Description
This is a single-arm, open-label study to evaluate the efficacy and safety of lenvatinib in combination with pembrolizumab and chemotherapy in patients with malignant pleural mesothelioma. The study will consist of a screening phase, a treatment phase, and a follow-up phase. Patients who meet the Inclusion Criteria, do not meet the Exclusion Criteria, and are judged by the investigator to be eligible for this clinical trial will be included. Subjects who meet all of the criteria listed in Criteria for Administration of Investigational Drugs may continue to receive the investigational drug. If a subject receiving investigational drugs meets any of the criteria listed in Discontinuation Criteria of Investigational Drugs, the subject will be evaluated at the end of the treatment phase (at the time of discontinuation) and moved to the post-observation phase.
Investigators
Prof. Kozo Kuribayashi, MD PhD
Professor
Hyogo Medical University
Eligibility Criteria
Inclusion Criteria
- •Patients with unresectable advanced or metastatic malignant pleural mesothelioma without prior treatment for malignant pleural mesothelioma
- •Patients expected to survive more than 90 days
- •Patients with a transcutaneous oxygen saturation of 94% or greater measured with a pulse oximeter at rest without oxygen inhalation within 7 days prior to enrollment
- •Patients who have given written consent to participate in this clinical trial (consent by a surrogate is also acceptable, if applicable).
- •Patients who are judged by the principal investigator or coinvestigator to have one or more measurable lesions as defined in Modified RECIST by CT or MRI imaging within 28 days prior to enrollment. However, if the measurable lesion is a pleural lesion only and there is a history of pleurodesis (patients who underwent pleurodesis within 14 days prior to enrollment or pleurodesis with Picibanil within 28 days prior to enrollment are excluded), only patients whose measurable lesion was confirmed on imaging after pleurodesis are eligible.
- •Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
- •Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention.
- •Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of malignant pleural mesothelioma will be enrolled in this study.
- •Have adequate organ function as defined in the following table. All clinical laboratory tests in the screening period should be performed within 10 days prior to the start of study intervention.
Exclusion Criteria
- •Patients with concomitant or pre-existing severe hypersensitivity reactions to other drugs, including antibody preparations
- •A women of childbearing potential who has a positive urine pregnancy test within 72 hours prior to trial registration. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- •Note: in the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication.
- •Has received prior therapy with an anti-PD-1 (anti-programmed cell death protein 1), anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX40, CD137).
- •Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to trial registration.
- •Note: Participants must have recovered from all adverse events (AEs) due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible. Participants with endocrine-related AEs Grade ≤2 requiring treatment or hormone replacement may be eligible Note: If the participant had major surgery, the participant must have recovered adequately from the procedure and/or any complications from the surgery prior to starting study intervention.
- •Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
- •Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
- •Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
- •Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
Arms & Interventions
Lenvatinib, Pemetrexed, Cisplatin/Carboplatin, and Pembrolizumab
In induction treatment, study interventions include oral lenvatinib, 8 mg quaque die (QD), and pembrolizumab, 200 mg, carboplatin (AUC 5 mg/mL/min) or cisplatin (75 mg/m2), and pemetrexed, 500 mg/m2 all given by intravenous (IV) infusion on Day 1 of a 21-day cycle. Lenvatinib, pembrolizumab, carboplatin/cisplatin, and pemetrexed combination treatment will be given for 4-6 cycles, after which participants may receive maintenance treatment with Lenvatinib, 20 mg QD, and pembrolizumab, 200 mg. Lenvatinib and Pembrolizumab may be given for up to a total of 35 cycles.
Intervention: Lenvatinib
Lenvatinib, Pemetrexed, Cisplatin/Carboplatin, and Pembrolizumab
In induction treatment, study interventions include oral lenvatinib, 8 mg quaque die (QD), and pembrolizumab, 200 mg, carboplatin (AUC 5 mg/mL/min) or cisplatin (75 mg/m2), and pemetrexed, 500 mg/m2 all given by intravenous (IV) infusion on Day 1 of a 21-day cycle. Lenvatinib, pembrolizumab, carboplatin/cisplatin, and pemetrexed combination treatment will be given for 4-6 cycles, after which participants may receive maintenance treatment with Lenvatinib, 20 mg QD, and pembrolizumab, 200 mg. Lenvatinib and Pembrolizumab may be given for up to a total of 35 cycles.
Intervention: Pemetrexed
Lenvatinib, Pemetrexed, Cisplatin/Carboplatin, and Pembrolizumab
In induction treatment, study interventions include oral lenvatinib, 8 mg quaque die (QD), and pembrolizumab, 200 mg, carboplatin (AUC 5 mg/mL/min) or cisplatin (75 mg/m2), and pemetrexed, 500 mg/m2 all given by intravenous (IV) infusion on Day 1 of a 21-day cycle. Lenvatinib, pembrolizumab, carboplatin/cisplatin, and pemetrexed combination treatment will be given for 4-6 cycles, after which participants may receive maintenance treatment with Lenvatinib, 20 mg QD, and pembrolizumab, 200 mg. Lenvatinib and Pembrolizumab may be given for up to a total of 35 cycles.
Intervention: Cisplatin/Carboplatin
Lenvatinib, Pemetrexed, Cisplatin/Carboplatin, and Pembrolizumab
In induction treatment, study interventions include oral lenvatinib, 8 mg quaque die (QD), and pembrolizumab, 200 mg, carboplatin (AUC 5 mg/mL/min) or cisplatin (75 mg/m2), and pemetrexed, 500 mg/m2 all given by intravenous (IV) infusion on Day 1 of a 21-day cycle. Lenvatinib, pembrolizumab, carboplatin/cisplatin, and pemetrexed combination treatment will be given for 4-6 cycles, after which participants may receive maintenance treatment with Lenvatinib, 20 mg QD, and pembrolizumab, 200 mg. Lenvatinib and Pembrolizumab may be given for up to a total of 35 cycles.
Intervention: Pembrolizumab
Outcomes
Primary Outcomes
Tumor shrinkage (response rate) (Physician Judgment by Medical Institution, Modified RECIST [Response Evaluation Criteria in Solid Tumors] criteria)
Time Frame: 2 years
The overall response and the best overall response are the result of the diagnostic imaging evaluated based on Modified RECIST criteria, and the result of the diagnostic imaging does not include clinical progression. The diagnostic imaging for which the overall response is determined other than inevaluable (NE) are considered as the evaluable diagnostic imaging. The response rate is defined as the proportion of participants who have complete response (CR) or partial response (PR).
Secondary Outcomes
- Best overall response (Physician Judgment by Medical Institution, Modified RECIST criteria)(2 years)
- Overall survival time (OS)(2 years)
- Tumor shrinkage (disease control rate) (Physician Judgment by Medical Institution, Modified RECIST criteria)(2 years)
- Incidence of adverse events(2 years)
- Progression-Free survival (PFS) (Physician Judgment by Medical Institution, Modified RECIST criteria)(2 years)
- Duration of response (Physician Judgment by Medical Institution, Modified RECIST criteria)(2 years)