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Untreated Advanced or Recurrent Thymic CarcinomasPhase 2ArtemisNCT05832827

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

A Phase 2 study testing MK-3475, Lenvatinib and Carboplatin in people with Untreated Advanced or Recurrent Thymic Carcinomas, run by National Cancer Center, Japan at 1 site in Japan.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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 Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
MK-3475, Lenvatinib and Carboplatin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
35 participants
Where
1 siteJapan
Study dates
4 Sep 2023to 30 Jun 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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.
  • 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.
  • 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.
  • 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.
  • Have adequate organ function as defined in the following table (Table 8). Specimens must be collected within 14 days prior to registration.
  • Have a predicted life expectancy of >12 weeks

Who cannot join

  • 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
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  • 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
  • Complication of Grade 3 or higher gastrointestinal or non-gastrointestinal fistula with CTCAE v5.0
  • History of Grade 3 or higher bleeding (site not specified) with CTCAE v5.0 within 28 days prior to registration
  • 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
  • Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation.
  • Gastrointestinal malabsorption or any other condition that might affect the absorption of lenvatinib
  • Active hemoptysis (bright red blood of at least 0.5 teaspoons) within 3 weeks prior to the first dose of the study drug
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • Has severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients
  • 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
  • Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
  • Has an active infection requiring systemic therapy
  • Has a known history of Human Immunodeficiency Virus (HIV) infection
  • 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
  • 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
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • 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
  • Has had an allogeneic tissue/solid organ transplant

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Yusuke Okuma, MD contact

+81-3-3542-2511

ncch2109_jimukyoku@is-pc.or.jp

Japan1 site, 1 recruiting

  • National Cancer Center Hospital

    Chūō, Tokyo, 104-0045

    Yusuke Okuma, MD, +81-3-3542-2511

    Yusuke Okuma, MD

    Recruiting

Other trials in Japan

About this study

Official title: 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

Read the 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.

Being tested
MK-3475, Lenvatinib, Carboplatin, Paclitaxel
Keywords
thymic carcinoma, pembrolizumab, lenvatinib
Medical subject headings
Thymoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MK-3475Drug

    Also called Keytruda/MK-3475 (Pembrolizumab)

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

  • LenvatinibDrug

    Also called Lenvima/MK-7902/E7080 (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.

  • CarboplatinDrug

    Also called CBDCA

    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.

  • PaclitaxelDrug

    Also called PTX

    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.

Study groups in NCT05832827
Study groupRoleWhat they receive
MK-3475(Pembrolizumab), Lenvatinib, carboplatin, and paclitaxelExperimentalIntervention: 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.
Receives: Drug: MK-3475; Drug: Lenvatinib; Drug: Carboplatin; Drug: Paclitaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: Up to 2 years

Secondary outcomes (4)

  1. Progression-free survival (PFS)

    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.

    Measured: Up to 2 years

  2. Overall Survival Rate (OS)

    The period from the registration date to the date of death due to any cause.

    Measured: Up to 2 years

  3. Duration of response (DoR)

    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.

    Measured: Up to 2 years

  4. Adverse event rate

    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.

    Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Apr 2023
  2. Study start4 Sep 2023
  3. Primary completion31 Dec 2025 (estimated)
  4. Study completion30 Jun 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
35 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05832827
Sponsor's protocol ID
NCCH2109
Acronym
Artemis
Status last verified
Oct 2023
First submitted
16 Apr 2023
Last updated
23 Oct 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Gandhi L, Garassino MC. Pembrolizumab plus Chemotherapy in Lung Cancer. N Engl J Med. 2018 Sep 13;379(11):e18. doi: 10.1056/NEJMc1808567. No abstract available.

    PubMed 30207917

  • Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med. 2003 Jun;9(6):669-76. doi: 10.1038/nm0603-669.

    PubMed 12778165

  • Ellis LM, Hicklin DJ. VEGF-targeted therapy: mechanisms of anti-tumour activity. Nat Rev Cancer. 2008 Aug;8(8):579-91. doi: 10.1038/nrc2403. Epub 2008 Jul 3.

    PubMed 18596824

  • Cross MJ, Claesson-Welsh L. FGF and VEGF function in angiogenesis: signalling pathways, biological responses and therapeutic inhibition. Trends Pharmacol Sci. 2001 Apr;22(4):201-7. doi: 10.1016/s0165-6147(00)01676-x.

    PubMed 11282421

  • Lieu C, Heymach J, Overman M, Tran H, Kopetz S. Beyond VEGF: inhibition of the fibroblast growth factor pathway and antiangiogenesis. Clin Cancer Res. 2011 Oct 1;17(19):6130-9. doi: 10.1158/1078-0432.CCR-11-0659. Epub 2011 Sep 27.

    PubMed 21953501

  • Phay JE, Shah MH. Targeting RET receptor tyrosine kinase activation in cancer. Clin Cancer Res. 2010 Dec 15;16(24):5936-41. doi: 10.1158/1078-0432.CCR-09-0786. Epub 2010 Oct 7.

    PubMed 20930041

  • Katsuya Y, Horinouchi H, Asao T, Kitahara S, Goto Y, Kanda S, Fujiwara Y, Nokihara H, Yamamoto N, Watanabe S, Tsuta K, Ohe Y. Expression of programmed death 1 (PD-1) and its ligand (PD-L1) in thymic epithelial tumors: Impact on treatment efficacy and alteration in expression after chemotherapy. Lung Cancer. 2016 Sep;99:4-10. doi: 10.1016/j.lungcan.2016.05.007. Epub 2016 May 12.

    PubMed 27565906

  • Cho J, Kim HS, Ku BM, Choi YL, Cristescu R, Han J, Sun JM, Lee SH, Ahn JS, Park K, Ahn MJ. Pembrolizumab for Patients With Refractory or Relapsed Thymic Epithelial Tumor: An Open-Label Phase II Trial. J Clin Oncol. 2019 Aug 20;37(24):2162-2170. doi: 10.1200/JCO.2017.77.3184. Epub 2018 Jun 15.

    PubMed 29906252

  • Giaccone G, Kim C, Thompson J, McGuire C, Kallakury B, Chahine JJ, Manning M, Mogg R, Blumenschein WM, Tan MT, Subramaniam DS, Liu SV, Kaplan IM, McCutcheon JN. Pembrolizumab in patients with thymic carcinoma: a single-arm, single-centre, phase 2 study. Lancet Oncol. 2018 Mar;19(3):347-355. doi: 10.1016/S1470-2045(18)30062-7. Epub 2018 Jan 26.

    PubMed 29395863

  • Travis WD, Brambilla E, Burke AP, Marx A, Nicholson AG. Introduction to The 2015 World Health Organization Classification of Tumors of the Lung, Pleura, Thymus, and Heart. J Thorac Oncol. 2015 Sep;10(9):1240-1242. doi: 10.1097/JTO.0000000000000663. No abstract available.

    PubMed 26291007

  • Detterbeck FC, Huang J. Overview. J Thorac Oncol. 2011 Jul;6(7 Suppl 3):S1689-90. doi: 10.1097/JTO.0b013e31821e7afe. No abstract available.

    PubMed 21847048

  • Girard N, Lal R, Wakelee H, Riely GJ, Loehrer PJ. Chemotherapy definitions and policies for thymic malignancies. J Thorac Oncol. 2011 Jul;6(7 Suppl 3):S1749-55. doi: 10.1097/JTO.0b013e31821ea5f7. No abstract available.

    PubMed 21847058

  • Detterbeck FC, Stratton K, Giroux D, Asamura H, Crowley J, Falkson C, Filosso PL, Frazier AA, Giaccone G, Huang J, Kim J, Kondo K, Lucchi M, Marino M, Marom EM, Nicholson AG, Okumura M, Ruffini E, Van Schil P; Staging and Prognostic Factors Committee; Members of the Advisory Boards; Participating Institutions of the Thymic Domain. The IASLC/ITMIG Thymic Epithelial Tumors Staging Project: proposal for an evidence-based stage classification system for the forthcoming (8th) edition of the TNM classification of malignant tumors. J Thorac Oncol. 2014 Sep;9(9 Suppl 2):S65-72. doi: 10.1097/JTO.0000000000000290.

    PubMed 25396314

  • Lemma GL, Lee JW, Aisner SC, Langer CJ, Tester WJ, Johnson DH, Loehrer PJ Sr. Phase II study of carboplatin and paclitaxel in advanced thymoma and thymic carcinoma. J Clin Oncol. 2011 May 20;29(15):2060-5. doi: 10.1200/JCO.2010.32.9607. Epub 2011 Apr 18.

    PubMed 21502559

  • Hirai F, Yamanaka T, Taguchi K, Daga H, Ono A, Tanaka K, Kogure Y, Shimizu J, Kimura T, Fukuoka J, Iwamoto Y, Sasaki H, Takeda K, Seto T, Ichinose Y, Nakagawa K, Nakanishi Y; West Japan Oncology Group. A multicenter phase II study of carboplatin and paclitaxel for advanced thymic carcinoma: WJOG4207L. Ann Oncol. 2015 Feb;26(2):363-8. doi: 10.1093/annonc/mdu541. Epub 2014 Nov 17.

    PubMed 25403584

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing MK-3475, Lenvatinib and Carboplatin in people with Untreated Advanced or Recurrent Thymic Carcinomas, run by National Cancer Center, Japan at 1 site in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 23 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Yusuke Okuma, MD (+81-3-3542-2511, ncch2109_jimukyoku@is-pc.or.jp), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Response Rate (RR) by the Blinded independent review committee (time frame: Up to 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05832827, which also lists 29 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Oct 2023.

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