Trial Title:
Study of Pembrolizumab Plus Chemotherapy With Lenvatinib for Malignant Pleural Mesothelioma
NCT ID:
NCT06318286
Condition:
Malignant Pleural Mesothelioma
Conditions: Official terms:
Mesothelioma
Mesothelioma, Malignant
Carboplatin
Pembrolizumab
Pemetrexed
Lenvatinib
Conditions: Keywords:
Pembrolizumab
Lenvatinib
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model 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. Patients 18 years of age or older will be eligible for enrollment if they
had histologically confirmed unresectable malignant pleural mesothelioma.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Lenvatinib
Description:
Induction treatment: lenvatinib, 8 mg QD on Day 1 of a 21-day cycle for 4-6 cycles.
Maintenance treatment: Lenvatinib, 20 mg QD may be given for up to a total of 35 cycles.
Arm group label:
Lenvatinib, Pemetrexed, Cisplatin/Carboplatin, and Pembrolizumab
Other name:
E7080
Intervention type:
Drug
Intervention name:
Pemetrexed
Description:
Pemetrexed, 500 mg/m2 will be given by intravenous (IV) infusion on Day 1 of a 21-day
cycle for 4-6 cycles.
Arm group label:
Lenvatinib, Pemetrexed, Cisplatin/Carboplatin, and Pembrolizumab
Intervention type:
Drug
Intervention name:
Cisplatin/Carboplatin
Description:
Carboplatin (AUC 5 mg/mL/min) or Cisplatin (75 mg/m2) will be given by IV infusion on Day
1 of a 21-day cycle for 4-6 cycles.
Arm group label:
Lenvatinib, Pemetrexed, Cisplatin/Carboplatin, and Pembrolizumab
Intervention type:
Drug
Intervention name:
Pembrolizumab
Description:
Pembrolizumab, 200 mg will be given by IV infusion on Day 1 of a 21-day cycle for up to a
total of 35 cycles.
Arm group label:
Lenvatinib, Pemetrexed, Cisplatin/Carboplatin, and Pembrolizumab
Other name:
MK-3475
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Patients with unresectable advanced or metastatic malignant pleural mesothelioma
without prior treatment for malignant pleural mesothelioma
2. Patients expected to survive more than 90 days
3. 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
4. Patients who have given written consent to participate in this clinical trial
(consent by a surrogate is also acceptable, if applicable).
5. 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.
6. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
Evaluation of ECOG is to be performed within 7 days prior to the first dose of study
intervention.
7. 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.
8. 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:
1. Patients with concomitant or pre-existing severe hypersensitivity reactions to other
drugs, including antibody preparations
2. 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.
3. 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).
4. 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.
5. 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.
6. 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.
7. 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.
8. Known additional malignancy that is progressing or has required active treatment
within the past 3 years. Note: Participants with basal cell carcinoma of the skin,
squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in
situ of the bladder, that have undergone potentially curative therapy are not
excluded.
9. Has known active central nervous system metastases and/or carcinomatous meningitis.
Participants with previously treated brain metastases may participate provided they
are radiologically stable, i.e. without evidence of progression for at least 4 weeks
by repeat imaging (note that the repeat imaging should be performed during study
screening), clinically stable and without requirement of steroid treatment for at
least 14 days prior to first dose of study intervention.
10. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its
excipients.
11. Has active autoimmune disease that has required systemic treatment in the past 2
years (i.e. with use of disease modifying agents, corticosteroids or
immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or
physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
12. Has a history of (non-infectious) pneumonitis/interstitial lung disease that
required steroids or has current pneumonitis/interstitial lung disease.
13. Has an active infection requiring systemic therapy.
14. Has a known history of Human Immunodeficiency Virus (HIV) infection.
15. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen
[HBsAg]reactive or HBV-DNA detected) or known active Hepatitis C virus (defined as
HCV RNA [qualitative] detected or HCV antibody reactive, if HCV-RNA is not the local
SOC) infection.
16. Has a history or current evidence of any condition, therapy, or laboratory
abnormality or other circumstance that might confound the results of the study,
interfere with the participant's participation for the full duration of the study,
such that it is not in the best interest of the participant to participate, in the
opinion of the treating investigator.
17. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
18. Is pregnant or breast feeding, or expecting to conceive or father children within
the projected duration of the study, starting with the screening visit through 120
days after the last dose of trial treatment.
19. Has had an allogenic tissue/solid organ transplant.
20. Patients with diverticulitis or symptomatic gastrointestinal ulcer disease
21. Patients with pleural effusions requiring drainage more frequently than once every 2
weeks
22. Patients with pericardial or ascites effusions requiring treatment
23. Patients with uncontrolled tumor-related pain
24. Patients with a history of transient ischemic attack, cerebral vascular attack,
thrombosis or thromboembolism (pulmonary artery embolism or deep vein thrombosis)
within 180 days prior to registration Patients with the following unmanageable or
serious cardiovascular diseases
- Myocardial infarction within 180 days prior to enrollment
- Uncontrolled angina pectoris within 180 days prior to enrollment
- New York Heart Association（NYHA）Classification of Cardiac Function
Classification III or IV congestive heart failure
- Uncontrolled hypertension (systolic blood pressure >150 mmHg or diastolic blood
pressure >90 mmHg for >24 hours) despite appropriate therapy
- Uncontrolled arrhythmia
25. Patients receiving anticoagulation therapy (excluding antiplatelet therapy including
low-dose aspirin) or with diseases requiring such therapy
26. Patients with uncontrolled diabetes mellitus
27. Patients undergoing surgical treatment with local or surface anesthesia within 14
days prior to enrollment
28. Patients undergoing surgical treatment involving general anesthesia within 28 days
prior to enrollment
29. Patients who underwent pleurodesis within 14 days prior to enrollment
30. Patients who underwent pleurodesis with picibanil within 28 days prior to enrollment
31. Patients who underwent pericardial adhesion within 28 days prior to enrollment
32. Patients who underwent peritoneal adhesions
33. Patients who received radiation therapy for pain relief within 14 days prior to
enrollment
34. Patients who have received radiopharmaceuticals (excluding the use of
radiopharmaceuticals for laboratory and diagnostic purposes) within 56 days prior to
enrollment
35. Patients who have received other unapproved drugs (including approved drugs not
indicated for malignant pleural mesothelioma, drugs administered through clinical
studies or unapproved combination drugs, or new formulations) within 28 days (90
days for antibody products) prior to enrollment
36. Patients with prolonged QT interval (QTc, corrected by Fridericia's formula) > 480
msec
37. Participants with proteinuria >1+ on urine dipstick testing/urinalysis will
undergo24-hour urine collection for quantitative assessment of proteinuria.
Participants with urine protein ≥1 g/24 hours will be ineligible.
38. Active hemoptysis (bright red blood ≥ 1/2 teaspoon) or other uncontrolled bleeding
within 14 days prior to the study registration.
39. Radiographic evidence of intratumoral cavitations, encasement, or invasion of a
major blood vessel. Additionally, the degree of proximity to major blood vessels
should be considered because for exclusion because of the potential risk of severe
hemorrhage associated with tumor shrinkage/necrosis after lenvatinib therapy. (In
the chest, major blood vessels include the main pulmonary artery, the left and right
pulmonary arteries, the 4 major pulmonary veins, the superior or inferior vena cava,
and the aorta).
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Hyogo Medical University Hospital
Address:
City:
Nishinomiya
Zip:
6638501
Country:
Japan
Contact:
Last name:
Kozo Kuribayashi, MD, PhD
Phone:
+81-798-45-6596
Email:
kuririn@hyo-med.ac.jp
Contact backup:
Last name:
Tetsuya Takagawa, MD, PhD
Phone:
+81- 798-45-6265
Email:
takagawa@hyo-med.ac.jp
Investigator:
Last name:
Nobukazu Fujimoto, MD, PhD
Email:
Principal Investigator
Investigator:
Last name:
Keisuke Aoe, MD, PhD
Email:
Principal Investigator
Start date:
March 13, 2024
Completion date:
October 30, 2026
Lead sponsor:
Agency:
Hyogo Medical University
Agency class:
Other
Collaborator:
Agency:
Merck Sharp & Dohme LLC
Agency class:
Industry
Source:
Hyogo Medical University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06318286
