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

October 18, 2023 updated by: National Cancer Center, Japan

First-line Carboplatin/Paclitaxel/Lenvatinib/Pembrolizumab Combination for Previously Untreated Advanced or Recurrent Thymic Carcinomas

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

35

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Japan
    • Tokyo
      • Chuo, Tokyo, Japan, 104-0045
        • Recruiting
        • National Cancer Center Hospital
        • Contact:
          • Yusuke Okuma, MD
          • Phone Number: +81-3-3542-2511
        • Principal Investigator:
          • Yusuke Okuma, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: MK-3475(Pembrolizumab), Lenvatinib, carboplatin, and paclitaxel
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
Pembrolizumab will be administered at a dose of 200 mg by intravenous infusion every 21 days (3 weeks) for up to 35 cycles.
Other Names:
  • Keytruda/MK-3475 (Pembrolizumab)
Drug: Lenvatinib
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.
Other Names:
  • Lenvima/MK-7902/E7080 (Lenvatinib)
Drug: Carboplatin
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.
Other Names:
  • CBDCA
Drug: Paclitaxel
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.
Other Names:
  • PTX

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response Rate (RR) by the Blinded independent review committee
Time Frame: Up to 2 years
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival (PFS)
Time Frame: Up to 2 years
The registration date shall be the starting date, and the period up to the earlier of date determined to be progression or the date of death due to any cause.
Up to 2 years
Overall Survival Rate (OS)
Time Frame: Up to 2 years
The period from the registration date to the date of death due to any cause.
Up to 2 years
Duration of response (DoR)
Time Frame: Up to 2 years
The progression-free survival rate at 1 year and 2nd year, and median DoR are calculated using the Kaplan-Meier method. The 95% confidence interval for the progression-free survival rate at 1 year and 2nd year is calculated using Greenwood's formula. The 95% confidence interval for the median DoR is determined using the Brookmeyer and Crowley method.
Up to 2 years
Adverse event rate
Time Frame: Up to 2 years
In the safety analysis target population, the frequency of the worst grade in all cycles according to the CTCAE v5.0 Japanese translation JCOG version is calculated for each adverse event and discontinuation by adverse events due to protocol treatment.
Up to 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Center, Japan

Collaborators

Merck Sharp & Dohme LLC

Investigators

  • Principal Investigator: Yusuke Okuma, MD, National Cancer Center, Japan

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 4, 2023

Primary Completion (Estimated)

December 31, 2025

Study Completion (Estimated)

June 30, 2028

Study Registration Dates

First Submitted

April 16, 2023

First Submitted That Met QC Criteria

April 16, 2023

First Posted (Actual)

April 27, 2023

Study Record Updates

Last Update Posted (Actual)

October 23, 2023

Last Update Submitted That Met QC Criteria

October 18, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCCH2109

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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