Trial Title:
First-line CBDCA/PTX/LEN/Pembrolizumab Combination for Previously Untreated Advanced or Recurrent Thymic Carcinomas (Artemis)
NCT ID:
NCT05832827
Condition:
Untreated Advanced or Recurrent Thymic Carcinomas
Conditions: Official terms:
Carcinoma
Thymoma
Recurrence
Paclitaxel
Carboplatin
Pembrolizumab
Lenvatinib
Conditions: Keywords:
thymic carcinoma
pembrolizumab
lenvatinib
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
MK-3475
Description:
Pembrolizumab will be administered at a dose of 200 mg by intravenous infusion every 21
days (3 weeks) for up to 35 cycles.
Arm group label:
MK-3475(Pembrolizumab), Lenvatinib, carboplatin, and paclitaxel
Other name:
Keytruda/MK-3475 (Pembrolizumab)
Intervention type:
Drug
Intervention name:
Lenvatinib
Description:
Lenvatinib will be administered at a dose of 8 mg orally QD every 21 days (3 weeks) for
up to 4 cycles in the induction phase, followed by 20 mg QD for up to 31 cycles in the
maintenance phase. Then, further maintenance therapy with lenvatinib will be allowed
until progression or unacceptable adverse events.
Arm group label:
MK-3475(Pembrolizumab), Lenvatinib, carboplatin, and paclitaxel
Other name:
Lenvima/MK-7902/E7080 (Lenvatinib)
Intervention type:
Drug
Intervention name:
Carboplatin
Description:
Carboplatin will be administered at a dose of AUC 5 intravenously every 21 days (3 weeks)
for up to 4 cycles in the induction phase.
Arm group label:
MK-3475(Pembrolizumab), Lenvatinib, carboplatin, and paclitaxel
Other name:
CBDCA
Intervention type:
Drug
Intervention name:
Paclitaxel
Description:
Paclitaxel will be administered at a dose of 175 mg/m^2 intravenously every 21 days (3
weeks) for up to 4 cycles in the induction phase.
Arm group label:
MK-3475(Pembrolizumab), Lenvatinib, carboplatin, and paclitaxel
Other name:
PTX
Summary:
A phase II, investigator-initiated, non-randomized, open-label, single-arm, multicenter
study to evaluate the efficacy and safety of
Carboplatin/Paclitaxel/Lenvatinib/Pembrolizumab combination for previously untreated
advanced or recurrent thymic carcinomas
Detailed description:
This is a phase II, investigator-initiated, non-randomized, open-label, single-arm,
multicenter study to evaluate the efficacy and safety of
Carboplatin/Paclitaxel/Lenvatinib/Pembrolizumab combination for previously untreated
advanced or recurrent thymic carcinomas.
Induction chemotherapy consists of carboplatin + paclitaxel + pembrolizumab + lenvatinib
for 3 weeks (21 days) as 1 cycle, up to a maximum of 4 cycles. Then, maintenance therapy
with pembrolizumab and lenvatinib will be continued until progression or unacceptable
adverse events.
Criteria for eligibility:
Criteria:
Inclusion 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.
Female participants:
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:
1. Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR
2. 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. Meet the following criteria for Hepatitis B and C Patients with no history of HBV or
HCV infection or who meet the following criteria 10.1 Hepatitis B positive subjects
Participants who are HBsAg positive are eligible if they have received HBV antiviral
therapy for at least 4 weeks and have an undetectable HBV viral load prior to
registration.
Participants should remain on anti-viral therapy throughout the study intervention
and follow local guidelines for HBV anti-viral therapy post-completion of the study
intervention.
10.2 Participants with a history of HCV infection Participants are eligible if HCV
viral load is undetectable at screening. Participants must have completed curative
anti-viral therapy at least 4 weeks prior to registration.
11. Have provided archival tumor tissue sample or newly obtained core or excisional
biopsy of a tumor lesion not previously irradiated. Formalin-fixed,
paraffin-embedded (FFPE) tissue blocks are preferred to slides. Newly obtained
biopsies are preferred to archived tissue.
12. 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.
13. Have adequate organ function as defined in the following table (Table 8). Specimens
must be collected within 14 days prior to registration.
14. Have a predicted life expectancy of >12 weeks
Exclusion 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. A WOCBP who has a positive urine pregnancy test within 72 hours prior to
registration (see Appendix 3). If the urine test is positive or cannot be confirmed
as negative, a serum pregnancy test will be required
6. Has urine protein ≥1 g/24 hours Note: Participants with proteinuria ≥2+ (≥100 mg/dL)
on urine dipstick testing (urinalysis) will undergo 24-hour urine collection for
quantitative assessment of proteinuria
7. Has had major surgery within 3 weeks prior to the first dose of study interventions
8. 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
9. Has any of the following a) to i):
1. History of interstitial pneumonia or evidence of interstitial lung disease
2. Uncontrollable autoimmune disease receiving chronic systemic steroid therapy
(in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy
3. History or complications of hypertensive crisis or hypertensive encephalopathy
4. Surgery under general anesthesia within 28 days before registration
5. History of total gastrectomy
6. Complication of congenital bleeding predisposition or abnormal coagulation
7. Complication of Grade 3 or higher gastrointestinal or non-gastrointestinal
fistula with CTCAE v5.0
8. History of Grade 3 or higher bleeding (site not specified) with CTCAE v5.0
within 28 days prior to registration
9. 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) *Antihypertensive drugs are counted by the number of compounds
10. Has radiographic evidence of encasement or invasion of a major blood vessel, or of
intratumoral cavitation.
11. Gastrointestinal malabsorption or any other condition that might affect the
absorption of lenvatinib
12. Active hemoptysis (bright red blood of at least 0.5 teaspoons) within 3 weeks prior
to the first dose of the study drug
13. Has received prior radiotherapy within 14 days before registration. Participants
must have recovered from all radiation-related toxicities, not require
corticosteroids, and not have had radiation pneumonitis. A 1-week washout is
permitted for palliative radiation (≤ 2 weeks of radiotherapy) to non-CNS disease
14. Has received a live vaccine or live-attenuated vaccine within 30 days prior to the
first dose of study drug. Administration of killed vaccines is allowed. Approved
COVID-19 vaccines (excluding live vaccines and/or live-attenuated vaccines) are
allowed
15. 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
16. 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
17. Has a known additional malignancy that is progressing or has required active
treatment within the past 3 years. Participants with basal cell carcinoma of the
skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast
carcinoma, cervical cancer in situ) that have undergone potentially curative therapy
are not excluded
18. Has known active CNS 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 the requirement of steroid treatment for at least 14 days prior
to the first dose of the study intervention
19. Has severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its
excipients
20. 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
21. Has a history of (non-infectious) pneumonitis/interstitial lung disease that
required steroids or has current pneumonitis/interstitial lung disease
22. Has an active infection requiring systemic therapy
23. Has a known history of Human Immunodeficiency Virus (HIV) infection
24. 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
25. Has a history or current evidence of any condition, therapy, or laboratory
abnormality that might confound the results of the study, interfere with the
participant's participation for the full duration of the study, or is not in the
best interest of the participant to participate, in the opinion of the treating
investigator
26. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial
27. 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
28. Has had an allogeneic tissue/solid organ transplant
Gender:
All
Gender based:
Yes
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
National Cancer Center Hospital
Address:
City:
Chuo
Zip:
104-0045
Country:
Japan
Status:
Recruiting
Contact:
Last name:
Yusuke Okuma, MD
Phone:
+81-3-3542-2511
Investigator:
Last name:
Yusuke Okuma, MD
Email:
Principal Investigator
Start date:
September 4, 2023
Completion date:
June 30, 2028
Lead sponsor:
Agency:
National Cancer Center, Japan
Agency class:
Other
Collaborator:
Agency:
Merck Sharp & Dohme LLC
Agency class:
Industry
Source:
National Cancer Center, Japan
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05832827
