Pembrolizumab and lenvatanib versus chemotherapy for advanced, recurrent, or metastatic endometrial cancer
- Conditions
- Advanced Endometrial CancerMedDRA version: 21.0Level: PTClassification code 10014733Term: Endometrial cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-003009-24-IT
- Lead Sponsor
- MERCK SHARP & DOHME CORP. UNA SUSSIDIARIA DI MERCK & CO. INC.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Female
- Target Recruitment
- 720
1. Have Stage III, Stage IV, or recurrent, histologically-confirmed endometrial carcinoma with disease that is either measurable or nonmeasurable per RECIST 1.1 but radiographically apparent, as assessed by BICR.
2. Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion that was not previously irradiated, for determination of MMR status.
3. Have an ECOG performance status of 0 or 1, as assessed within 7 days prior to the first dose of study intervention.
4. Be female and at least 18 years of age on the day of signing consent.
5. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
- Is not a WOCBP OR
- Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), during the intervention period and for at least 120 days post pembrolizumab or 30 days post lenvatinib, whichever occurs last, and 196 days after the last dose of chemotherapy. The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in
relationship to the first dose of study intervention
- A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first dose of study intervention.
- If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
6. The participant (or legally acceptable representative if applicable) provides written informed consent for the study.
7. Have adequately controlled BP with or without antihypertensive medications, defined as BP =150/90 mm Hg with no change in antihypertensive medications within 1 week prior to randomization.
8. Have adequate organ function within 7 days prior to the first dose of study intervention.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 170
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 550
1. Has carcinosarcoma (malignant mixed Mullerian tumor), endometrial leiomyosarcoma or other high grade sarcomas, or endometrial stromal sarcomas.
2. Participants with central nervous system (CNS) metastases are not eligible, unless they have completed local therapy and have discontinued the use of corticosteroids for this indication for at least 4 weeks before starting treatment in this study. Any signs or symptoms of CNS metastases must be stable for at least 4 weeks before starting study treatment.
3. Has a known additional malignancy (other than endometrial carcinoma) that is progressing or has required active treatment in the last 3 years.
4. Has gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib.
5. Has a pre-existing Grade =3 gastrointestinal or non-gastrointestinal fistula.
6. Has radiographic evidence of major blood vessel invasion/infiltration. The degree of tumor invasion/infiltration of major blood vessels should be considered because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis following lenvatinib therapy.
7. Has clinically significant hemoptysis or tumor bleeding within 2 weeks prior to randomization.
8. Has significant cardiovascular impairment within 12 months of the first dose of study intervention such as history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction or cerebrovascular accident (CVA) stroke, or cardiac arrhythmia associated with hemodynamic instability.
9. Has an active infection (any infection requiring systemic treatment).
10. Has had major surgery within 3 weeks prior to first dose of study interventions.
11. Has not recovered adequately from any toxicity and/or complications from major surgery prior to randomization.
12. Has a known history of human immunodeficiency virus (HIV) infection.
13. Has a known history of Hepatitis B or known active Hepatitis C virus infection.
14. Has a history of (non-infectious) pneumonitis that required treatment with steroids, or has current pneumonitis.
15. Has a known history of active tuberculosis
16. 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.
17. Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study.
18. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to randomization.
19. Has an active autoimmune disease (with the exception of psoriasis) that has required systemic treatment in the past 2 years. Replacement therapy is not considered a form of systemic treatment.
20. Is pregnant or breastfeeding or expecting to conceive children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of pembrolizumab or 30 days post lenvatinib, whichever occur last, and 196 days after the last dose of chemotherapy.
21. Has received prior systemic chemotherapy in any setting for the treatment of endometrial carcinoma.
22. Has received prior radiotherapy within 4 weeks prior to randomiza
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method