EUCTR2019-003444-72-DK进行中（未招募）1 期
An Open-label, Randomized Phase 3 Study of MK-6482 Versus Everolimus in Participants with Advanced Renal Cell Carcinoma That Has Progressed After Prior PD- 1/L1 and VEGF-Targeted Therapies
适应症
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 736
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional clinical trial of medicinal product
入排标准
- 性别
- All
入选标准
- •1. Has unresectable, locally advanced or metastatic clear cell RCC
- •2. Has measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology. Lesions situated in a previously irradiated area are considered measurable if progression has been shown in such lesions
- •3. Has had disease progression on or after having received systemic treatment for locally advanced or metastatic RCC with both: PD-1/L1 checkpoint inhibitor and VEGF-TKI in sequence or in combination.
- •PD-1/L1 checkpoint inhibitor treatment progression is defined by meeting ALL of the following criteria:
- •o Has received at least 2 doses of an anti- PD-1/L1 mAb
- •o Has demonstrated radiographic PD during or after an anti- PD-1/L1
- •VEGF-TKI treatment progression is defined by meeting the following
- •o Has demonstrated radiographic PD during or after a treatment with a
- •4. Has received no more than 3 prior systemic regimens for locally advanced or metastatic RCC
- •5. For the most recently received regimen, has demonstrated disease progression as defined by RECIST 1.1
- •6. Is male or female, who is at least 18 years of age at the time of signing the informed consent
- •7. Has a KPS score of at least 70% assessed within 10 days prior to randomization.
- •8. Male participants are eligible to participate if they agree to the
- •following during the intervention period and for at least 7 days after the
- •last dose of study intervention:
- •Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent.
- •Must agree to use contraception unless confirmed to be azoospermic
- •(vasectomized or secondary to medical cause as detailed below:
- •o Agree to use a male condom plus partner use of an additional
- •contraceptive method when having penile-vaginal intercourse with a
- •WOCBP who is not currently pregnant. Note: Men with a pregnant or
- •breastfeeding partner must agree to remain abstinent from penilevaginal
- •intercourse or use a male condom during each episode of penilevaginal
- •penetration.
- •9. 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
- •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 30 days after the last dose of study
- •intervention for those randomized to the belzutifan study intervention
- •and for at least 8 weeks after last dose of study intervention for those
- •randomized to the everolimus arm. 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)
- •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
- •test is positive.
- •Additional requirements for pregnancy testing during and after study
- •intervention are in the Schedule of Activities.
- •The investigator is responsible f
排除标准
- •1. A WOCBP who has a positive urine pregnancy test within 24 hours prior to randomization. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
- •2. Has any of the following:
- •Hypoxia as defined by pulse oximeter reading <92% at rest, OR
- •Requires intermittent supplemental oxygen, OR
- •Requires chronic supplemental oxygen.
- •3. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
- •4. Has known CNS metastases and/or carcinomatous meningitis
- •5. Has clinically significant cardiac disease, including unstable angina, acute myocardial infarction within 6 months from Day 1 of study medication administration, or New York Heart Association Class III or IV congestive heart failure. Medically controlled arrhythmia stable on medication is permitted
- •6. Has poorly controlled hypertension defined as SBP =150 mm Hg and/or DBP =90 mm Hg
- •7. Has moderate to severe hepatic impairment (Child-Pugh B or C)
- •8. Received colony-stimulating factors (eg, G-CSF, GM-CSF or recombinant EPO) within 28 days prior to the first dose of study intervention
- •9. Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study
- •10. Is unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption (eg, gastrectomy, partial bowel obstruction, malabsorption)
- •11. Has known hypersensitivity or allergy to the active pharmaceutical ingredient or any component of the study intervention (belzutifan or everolimus) formulations
- •12. Has received prior treatment with belzutifan or another HIF-2a inhibitor
- •13. Has received prior treatment with everolimus or any other specific or selective TORC1/PI3K/AKT inhibitor (eg, temsirolimus) in the advanced disease setting
- •14. Has received any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before randomization
- •15. Has received any type of systemic anticancer antibody (including investigational antibody) within 4 weeks before randomization
- •16. Has received prior radiotherapy within 2 weeks prior to first dose of study intervention. Participants must have recovered from all radiation-related toxicities and not require corticosteroids. A 1-week washout is required for palliative radiation (=2 weeks of radiotherapy) to non-CNS disease
- •17. Has had major surgery within 3 weeks prior to randomization
- •18. Has received a live vaccine within 30 days prior to the randomization of study medication. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, BCG, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®/Fluenz Tetra) are live attenuated vaccines and are not allowed
- •19. Is currently receiving either strong (eg, itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate (eg, ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil) inhibitors of CYP3A4 that cannot be discontinued for the duration of the study
- •20. Is currently receiving either strong (phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John’s Wort) o
研究者
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