First-line CBDCA/PTX/LEN/Pembrolizumab Combination for Previously Untreated Advanced or Recurrent Thymic Carcinomas (Artemis)

NCT05832827 | Recruiting Phase 2 DMC

• 1 other identifier: NCCH2109
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Untreated Advanced or Recurrent Thymic Carcinomas

Keywords

thymic carcinoma; pembrolizumab; lenvatinib

Outcome Measures

Primary Outcomes (1)

• Response Rate (RR) by the Blinded independent review committee

  RR is defined as the proportion of patients with the best overall response to complete response (CR) or partial response (PR) as evaluated by the independent review committee according to RECIST 1.1

  Up to 2 years

Secondary Outcomes (4)

• Progression-free survival (PFS)

  Up to 2 years

• Overall Survival Rate (OS)

  Up to 2 years

• Duration of response (DoR)

  Up to 2 years

• Adverse event rate

  Up to 2 years

Study Arms (1)

MK-3475(Pembrolizumab), Lenvatinib, carboplatin, and paclitaxel

EXPERIMENTAL

Intervention: 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.

Drug: MK-3475; Drug: Lenvatinib; Drug: Carboplatin; Drug: Paclitaxel

Interventions

MK-3475 DRUG

Pembrolizumab will be administered at a dose of 200 mg by intravenous infusion every 21 days (3 weeks) for up to 35 cycles.

Also known as: Keytruda/MK-3475 (Pembrolizumab)

MK-3475(Pembrolizumab), Lenvatinib, carboplatin, and paclitaxel

Lenvatinib DRUG

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.

Also known as: Lenvima/MK-7902/E7080 (Lenvatinib)

MK-3475(Pembrolizumab), Lenvatinib, carboplatin, and paclitaxel

Carboplatin DRUG

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.

Also known as: CBDCA

MK-3475(Pembrolizumab), Lenvatinib, carboplatin, and paclitaxel

Paclitaxel DRUG

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.

Also known as: PTX

MK-3475(Pembrolizumab), Lenvatinib, carboplatin, and paclitaxel

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• No symptomatic brain metastases, carcinomatous meningitis, or spinal metastases requiring radiotherapy or surgery
• No prior history of an antiangiogenetic agent targeting VEGFR for thymic carcinoma
• Not receiving radiotherapy within 14 days before registration Male participants
• 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:
• 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:
• Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR
• 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.
• The participant provides written informed consent for the trial
• 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
• 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.

You may not qualify if:

• Has diagnosed as thymomas
• Has related immune-related complications such as myasthenia gravis, pure red cell aplasia, or hypogammaglobulinemia
• Patients with ECG QT correction interval prolongation or history of such prolongation (patients with QTcF \> 480 ms)
• Has a LVEF below the institutional normal range, as determined by multigated acquisition (MUGA) or echocardiogram (ECHO)
• 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
• 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
• Has had major surgery within 3 weeks prior to the first dose of study interventions
• 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
• Has any of the following a) to i):
• History of interstitial pneumonia or evidence of interstitial lung disease
• Uncontrollable autoimmune disease receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy
• History or complications of hypertensive crisis or hypertensive encephalopathy
• Surgery under general anesthesia within 28 days before registration
• History of total gastrectomy
• Complication of congenital bleeding predisposition or abnormal coagulation

Sponsors & Collaborators

• National Cancer Center, Japan: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

National Cancer Center Hospital

Chūō, Tokyo, 104-0045, Japan

RECRUITING

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MeSH Terms

Conditions

Thymoma

Interventions

pembrolizumab; lenvatinib; Carboplatin; Paclitaxel

Condition Hierarchy (Ancestors)

Neoplasms, Complex and Mixed; Neoplasms by Histologic Type; Neoplasms; Thymus Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lymphatic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• Yusuke Okuma, MD

  National Cancer Center, Japan

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yusuke Okuma, MD

CONTACT

+81-3-3542-2511; ncch2109_jimukyoku@is-pc.or.jp

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2023
• First Posted: April 27, 2023
• Study Start: September 4, 2023
• Primary Completion: December 31, 2025
• Study Completion (Estimated): June 30, 2028
• Last Updated: October 23, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

JP (1)