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Combination of Pembrolizumab and Lenvatinib, in Pre-treated Thymic CArcinoma paTIents (PECATI)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04710628
Recruitment Status : Recruiting
First Posted : January 15, 2021
Last Update Posted : January 19, 2023
Sponsor:
Collaborator:
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
MedSIR

Brief Summary:
This is a multicentric, open-label, single arm phase II study to evaluate the efficacy and safety of the combination of pembrolizumab and lenvatinib in pre-treated thymic carcinoma patients who have progressed after at least one line of platinum-based chemotherapy for advanced disease without having received any previous immunotherapy (previous bevacizumab allowed, but not sunitinib), and not amenable to curative-intent radical surgery and/or radiotherapy, regardless of PD-L1 status.

Condition or disease Intervention/treatment Phase
Metastatic Thymic Carcinoma Thymoma Type B3 Drug: Pembrolizumab Drug: Lenvatinib 10 mg Phase 2

Detailed Description:
Men and women aged ≥ 18 years old diagnosed with B3-thymoma or metastatic thymic carcinoma who have progressed after at least one line of platinum-based chemotherapy for advanced disease without having received any previous immunotherapy (previous bevacizumab allowed, but not sunitinib), and not amenable to curative-intent radical surgery and/or radiotherapy, regardless of PD- L1 status. Presence of measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v.)1.1 criteria. Patients are not eligible if they are candidates for a local treatment with a curative intention. Patients must present Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 and with adequate organ function.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 43 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicentric, Open-Label, Single Arm Phase II Study To Evaluate The Efficacy And Safety Of The Combination Of PEmbrolizumab And Lenvatinib In Pre-Treated Thymic Carcinoma PaTIents. PECATI.
Actual Study Start Date : September 21, 2021
Estimated Primary Completion Date : June 2023
Estimated Study Completion Date : October 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: PEMBROLIZUMAB + LENVATINIB

Pembrolizumab 200 mg will be administered to patients as 30-minute IV infusion every 3 weeks (a window of -5 minutes and +10 minutes is permitted).

Lenvatinib 20 mg (2 capsules of 10 mg) will be administered daily at the same time, with or without food. At the day 1 of each cycle, lenvatinib will be administered within 4 hours after finishing pembrolizumab (lenvatinib after pembrolizumab). Lenvatinib cannot be chewed

Drug: Pembrolizumab
Pembrolizumab 200 mg will be administered to patients as 30-minute intravenous infusion (a window of -5 minutes and +10 minutes is permitted) every 3 weeks.
Other Name: MK-3475, lambrolizumab

Drug: Lenvatinib 10 mg
Lenvatinib 20 mg (2 capsules of 10 mg) will be administered daily at the same time, with or without food. At the day 1 of each cycle, lenvatinib will be administered within 4 hours after finishing pembrolizumab (lenvatinib after pembrolizumab)
Other Name: E7080




Primary Outcome Measures :
  1. Progression-free survival (PFS) [ Time Frame: 5 months ]
    PFS rate at 5 months, defined as the percentage of patients with B3-Thymoma and Thymic Carcinoma without disease progression at 5 months after starting the treatment combination.


Secondary Outcome Measures :
  1. Response rate (RR) [ Time Frame: 5 months ]
    RR with the treatment combination

  2. Maximum tumor shrinkage (MTS) [ Time Frame: 5 months ]
    MTS with the treatment combination

  3. Disease control rate (DCR) [ Time Frame: 5 months ]
    DCR with the treatment combination

  4. Duration of response (DoR) [ Time Frame: 5 months ]
    DoR with the treatment combination

  5. Overall survival (OS) [ Time Frame: 2 years ]
    OS

  6. Incidence of Grade 3 and 4 AEs and SAEs [ Time Frame: 2 years ]
    Grade 3 and 4 AEs and serious adverse events (SAEs) will be assessed, according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v.5.0), to determine the safety and tolerability of the combination.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Participants are eligible to be included in the study only if all of the following criteria apply:

  1. Relapsed / Recurrent histologically confirmed B3-Thymoma or TC patients not amenable to curative-intent radical surgery and/or radiotherapy, regardless of PD-L1 expression.
  2. Patients progress after at least one previous line of platinum-based chemotherapy for advanced disease:

    a. Patients treated with neo-adjuvant or adjuvant platinum-based chemotherapy combined with radical surgery or as part of radical chemo-radiotherapy are eligible if chemotherapy was completed within 6 months before enrollment.

  3. Negative result for Myasthenia Gravis (MG) by acetylcholine receptor antibodies test.
  4. Male/female who are at least 18 years of age on the day of signing informed consent.
  5. ECOG performance status 0-1
  6. Life expectancy ≥ 3 months
  7. Radiological progression documented per RECIST 1.1 during or after completion of previous line therapy, per investigator's criteria.
  8. Presence of measurable disease according to RECIST criteria. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.

    a. Disease status must be documented by full chest and upper abdomen (including adrenal glands) CT and/or MRI within 28 days prior study enrollment. If clinically indicated, brain imaging must be performed;

  9. Provides historical (obtained archived FFPE) or fresh tumor biopsy specimen for biomarker studies, if feasible. Archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated is acceptable. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archival tissue. Note: If submitting unstained cut slides, newly cut slides should be submitted to the testing laboratory within 14 days from the date slides are cut.
  10. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:

    1. Not a woman of childbearing potential (WOCBP) OR
    2. A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 6 months after the last dose of study treatment.
  11. Has adequate bone marrow and organ function. Specimens must be collected within 10 days prior to the start of study treatment.
  12. Written informed consent prior to beginning specific protocol procedures.

Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply:

  1. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137).
  2. Has received prior therapy with sunitinib.
  3. Any evidence of active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are clinically stable (i.e. without evidence of progression by imaging for at least four weeks prior to enrollment and any neurologic symptoms have returned to baseline), and have not received steroids (for a total equivalent dose of more than 10 mg of prednisone per day) for at least 7 days prior to enrollment.
  4. Uncontrolled blood pressure (Systolic BP>140 mmHg or diastolic BP >90 mmHg) in spite of an optimized regimen of antihypertensive medication.
  5. Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction or stroke within 6 months of the first dose of study drug, or cardiac arrhythmia requiring medical treatment at Screening.
  6. Intratumor cavitation, direct invasion of main mediastinal blood vessels by the tumor or exist previous bleeding.
  7. Subjects having > 1+ proteinuria on urine dipstick testing unless a 24-hour urine collection for quantitative assessment indicates that the urine protein is <1 g/24 hours.
  8. Has received prior investigational agents within 4 weeks prior to allocation.
  9. Participants must have recovered from all AEs due to previous therapies to ≤ Grade 1 or baseline. Participants with ≤ Grade 2 neuropathy may be eligible.
  10. If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment. If surgery is needed during treatment, lenvatinib will be withheld for at least 1 week prior to elective surgery and until at least 2 weeks following major surgery and adequate wound healing. The safety of resumption of lenvatinib after resolution of wound healing has not been established.
  11. Fraction ejection < 50%.
  12. Known history or current evidence of active Hepatitis B (e.g., HBsAg reactive) or C (e.g., HCV RNA [qualitative] is detected) or Human Immunodeficiency Virus (HIV) (HIV-1/2 antibodies).
  13. If CT has to be used, known contra-indications for CT with IV contrast.
  14. Chronic use of immunosuppressive agents and/or systemic corticosteroids or any use in the last 15 days prior to enrolment:

    a. Daily prednisone at doses up to 10 mg or equivalent doses of any other corticosteroid is allowed for example as replacement therapy.

  15. History of interstitial lung disease (ILD) OR pneumonitis (other than COPD exacerbation) that has required oral or IV steroids.
  16. Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (i.e., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
  17. Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
  18. Autoimmune disorders requiring immunosuppressive or dedicated treatment.
  19. History of any other hematologic or primary solid tumor malignancy, unless in remission for at least 5 years and without specific treatment (as example, not allowed hormonal therapy to replace for breast cancer or hormonal therapy substitution in prostate cancer). pT1-2 prostatic cancer Gleason score < 6, superficial bladder cancer, non-melanomatous skin cancer or carcinoma in situ of the cervix are allowed.
  20. Previous allogenic tissue/solid organ transplantation
  21. Active infection requiring systemic therapy
  22. A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

    Note: in the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication.

  23. Has received prior radiotherapy within 2 weeks of start of study treatment.
  24. Has severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients; known sensitivity or intolerance to lenvatinib and/or any of its excipients; severe hypersensitivity to monoclonal antibody-containing regimen.
  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 subject's participation for the full duration of the study, or is not in the best interest of the subject 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. Has an intestinal disease not allowing swallowing pills.
  28. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through the 6 months after the last dose of trial treatment.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04710628


Contacts
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Contact: Neus Crespo +34 623 333 632 neus.crespo@medsir.org
Contact: Alicia García-Sanz +34 611 261 467 alicia.garcia@medsir.org

Locations
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France
Institut Bergonié Recruiting
Bordeaux, France
Contact: Sophie Cousin         
Principal Investigator: Sophie Cousin         
Hôpitaux Universitaires de Marseille - Hôpital Nord Not yet recruiting
Marseille, France
Contact: Laurent Greillier         
Principal Investigator: Laurent Greillier         
Institut Curie Not yet recruiting
Paris, France
Contact: Nicolas Girard         
Principal Investigator: Nicolas Girard         
Centre Hospitalier Universitaire de Toulouse Recruiting
Toulouse, France
Contact: Laurence Bigay-Game         
Principal Investigator: Laurence Bigay-Game         
IGR Gustave Roussy Recruiting
Villejuif, France
Contact: Benjamin Besse         
Principal Investigator: Benjamin Besse         
Italy
A.O.U. San Luigi Gonzaga Recruiting
Orbassano, Italy
Contact: Silvia Novello         
Principal Investigator: Silvia Novello         
Spain
Hospital Clinic i Provincial de Barcelona Recruiting
Barcelona, Spain, 08036
Contact: Noemí Reguart         
Principal Investigator: Noemí Reguart         
Complejo Hospitalario Universitario A Coruña (CHUAC) Recruiting
La Coruña, Spain
Contact: Maria Rosario Campelo         
Principal Investigator: Maria Rosario Campelo         
Hospital Universitario La Paz Recruiting
Madrid, Spain
Contact: Javier De Castro         
Principal Investigator: Javier De Castro         
Hospital Universitario Virgen del Rocío Recruiting
Sevilla, Spain
Contact: Reyes Bernabé         
Principal Investigator: Reyes Bernabé         
Hospital Universitari i Politècnic La Fe Recruiting
Valencia, Spain
Contact: Oscar Juan         
Principal Investigator: Oscar Juan         
Sponsors and Collaborators
MedSIR
Merck Sharp & Dohme LLC
Investigators
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Principal Investigator: Jordi Remon, MD, PhD HM-CIOCC, Hospital HM Delfos, HM Hospitales, Barcelona (Spain)
Principal Investigator: Benjamin Besse, MD, PhD Medical Oncology Department Gustave Roussy, Villejuif (France)
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Responsible Party: MedSIR
ClinicalTrials.gov Identifier: NCT04710628    
Other Study ID Numbers: MedOPP341
First Posted: January 15, 2021    Key Record Dates
Last Update Posted: January 19, 2023
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Carcinoma
Thymoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Complex and Mixed
Thymus Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lymphatic Diseases
Pembrolizumab
Lenvatinib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action