NCCH2109

JRCT ID: jRCT2031230114

Registered date:07/06/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Untreated advanced or recurrent thymic carcinomas
• Date of first enrollment: 16/10/2023
• Target sample size: 35
• Study type: Interventional
• Intervention(s): Carboplatin + paclitaxel + pembrolizumab + lenvatinib for 3 weeks (21 days) as 1 cycle, up to a maximum of 4 cycles in the induction phase. Then, maintenance therapy with pembrolizumab and lenvatinib will be continued until progression or unacceptable adverse events up to 31 cycles.

Outcome(s)

• Primary Outcome: Objective Response Rate
• Secondary Outcome: Progression-free survival (PFS), Overall Survival Rate (OS), Duration of response (DoR), Adverse event rate

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. Patients aged 18 years or older at the time of informed consent, who are pathologically (histologically or cytologically) diagnosed with thymic carcinoma for primary or metastatic thymic lesions, are included. They are preferred to be positive for CD5 or c-KIT by immunohistochemical staining. For those with non-squamous epithelial carcinoma negative for p40 or p63, non-primary cases should be excluded based on their clinical and pathological findings. In addition, those with thymoma are excluded.
2. Patients with unresectable advanced thymic carcinoma (equivalent to stage IVa or IVb of Masaoka-Koga classification), metastatic or recurrent, who have not been treated with systemic cancer chemotherapy.
Or, in the case of stage III Masaoka-Koga classification, patients who are judged to be incapable of radical resection (R0 resection is not possible due to the combined resection of invasive lesions in surrounding organs (pericardial sac, lung, great vessels, etc.) or who are not eligible for curative treatment with chemoradiotherapy. A history of adjuvant chemotherapy and radiation therapy is acceptable for perioperative adjuvant therapy prior to the finding of recurrence. If platinum-containing cancer chemotherapy has been administered as adjuvant therapy, it is eligible if there is an interval of at least 24 weeks before registration.
3. No symptomatic brain metastases, carcinomatous meningitis, or spinal metastases requiring radiotherapy or surgery
4. No prior history of an antiangiogenetic agent targeting VEGFR for thymic carcinoma
5. Not receiving radiotherapy within 14 days before registration Male participants
6. A male participant must agree to use contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 135 days after the last dose of study treatment and refrain from donating sperm during this period.
7. A female participant is eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies:
a) Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR
b) A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 120 days after the last dose of study treatment.
8.The participant provides written informed consent for the trial
9. Have measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
10. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 14 days before registration.
11. Have a predicted life expectancy of >12 weeks

Exclude criteria

1. Has diagnosed as thymomas
2. Has related immune-related complications such as myasthenia gravis, pure red cell aplasia, or hypogammaglobulinemia
3. Patients with ECG QT correction interval prolongation or history of such prolongation (patients with QTcF > 480 ms)
4. Has a LVEF below the institutional normal range, as determined by multigated acquisition (MUGA) or echocardiogram (ECHO)
5. Has urine protein >= 1 g/24 hours
6. Has had major surgery within 3 weeks prior to the first dose of study interventions
7. Has clinically significant cardiovascular disease within 12 months from the first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability
8. Has any of the following a) to i):
a) History of interstitial pneumonia or evidence of interstitial lung disease
b) Uncontrollable autoimmune disease receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy
c) History or complications of hypertensive crisis or hypertensive encephalopathy
d) Surgery under general anesthesia within 28 days before registration
e) History of total gastrectomy
f) Complication of congenital bleeding predisposition or abnormal coagulation
g) Complication of Grade 3 or higher gastrointestinal or non-gastrointestinal fistula with CTCAE v5.0
h) History of Grade 3 or higher bleeding (site not specified) with CTCAE v5.0 within 28 days prior to registration
i) Blood pressure is not well controlled (with 2 or fewer antihypertensive drugs 2, systolic blood pressure is 150 mmHg or less and diastolic blood pressure is 90 mmHg or less)
9. Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation.
10. Gastrointestinal malabsorption or any other condition that might affect the absorption of lenvatinib
11. Active hemoptysis (bright red blood of at least 0.5 teaspoons) within 3 weeks prior to the first dose of the study drug
12. 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 the study drug
13. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with the use of disease-modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed
14. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
15. Concurrent active Hepatitis B ( defined as HBsAg positive and detectable HBV DNA) and Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection
16. Is pregnant or breastfeeding or expecting to conceive within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment. Is expecting to father children within 135 days after the last dose of trial treatment

Related Information

• Primary Sponsor: Okuma Yusuke
• Source(s) of Monetary Support: Merck Sharp & Dohme LLC
• Secondary ID(s): NCT05832827