EUCTR2018-002275-18-DE进行中（未招募）1 期
A multicenter study with an open-label Phase Ib part followed by a randomized, placebo-controlled, double-blind, Phase II part to evaluate efficacy,safety, tolerability, and pharmacokinetics of the DNA-PK inhibitor M3814 in combination with capecitabine and radiotherapy in participants withlocally advanced rectal cancer
适应症
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- Merck KGaA
- 入组人数
- 150
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
- •Participants are eligible to be included in the study only if all the following criteria apply:
- •1. Are = 18 years of age, at the time of signing the informed consent
- •Type of Participant and Disease Characteristics
- •2. Have an Eastern Cooperative Oncology Group Performance Status = 1
- •3. Have histologically confirmed and localized resectable rectal cancer (Stage II or Stage III at original staging). Participants who received induction chemotherapy are allowed to be enrolled to this study except if this induction is resulting in complete response (as per tumor evaluation charter).
- •4. Have lower edge of the tumor located in rectum
- •5. Have evaluable disease in MRI
- •6. Have adequate hematological function: hemoglobin = 9 g/dL, neutrophils = 1.5 × 109/L and platelets = 100 × 109/L
- •7. Have adequate renal function: serum creatinine = 1.5 × upper limit of normal (ULN) or creatinine clearance = 50 mL/min
- •8. Have adequate liver function: aspartate aminotransferase, alanine transaminase, alkaline phosphatase = 3 × ULN, and bilirubin = 1.5 × ULN
- •9. Are male or female
- •? Male participants:
- •Agree to the following during the study intervention period and for at least 12 weeks after the last dose of study intervention:
- •o Refrain from donating sperm
- •Plus, either:
- •o Abstain from any activity that allows for exposure to ejaculate.
- •o Use a male condom:
- •? When having sexual intercourse with a WOCBP, who is not currently pregnant, and advise her to use a highly effective contraceptive method with
- •a failure rate of <1% per year, since a condom may break or leak.
- •? When engaging in any activity that allows for exposure to ejaculate.
- •? Female Participants:
- •o Are not pregnant or breastfeeding, and at least one of the following conditions applies:
- •? Not a WOCBP
- •? If a WOCBP, use a highly effective contraceptive method (i.e., with a failure rate of <1% per year), preferably with low user dependency, as
- •described for the following time periods:
- •o Before the first dose of the study intervention(s), if using hormonal contraception:
- •? Has completed at least one 4-week cycle of an oral contraception pill and either had or has begun her menses
- •? Has used a depot contraceptive or extended-cycle oral contraceptive for least 28 days and has a documented negative pregnancy test using a highly
- •sensitive assay.
- •? A barrier method.
- •o During the intervention period
- •o After the study intervention period (i.e., after the last dose of study intervention is administered) for at least 12 weeks, after the last dose of study intervention and agree not to donate eggs (ova, oocytes) for reproduction during this period.
- •The Investigator evaluates the effectiveness of the contraceptive method in relationship to the first dose of study intervention.
- •o Have a negative serum pregnancy test, as required by local regulations, within 4 weeks before the first dose of study intervention. Additional requirements for pregnancy testing during and after study intervention .
- •-The Investigator reviews the medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a female with an early undetected pregnancy.
- •Informed Consent
- •10. Can give signed informed consent, which includes compliance with the requirements and restrictions listed in an informed consent
- •form (ICF) and this protocol.
- •Are the trial subjects under 18? no
- •Number of subjects for this age range:
- •F.1.2 Adults (18-64 years) yes
排除标准
- •Participants are excluded from the study if any of the following criteria apply:
- •Medical Conditions
- •1. History of any other significant medical disease or psychiatric conditions that might in the assessment of the Investigator preclude safe participation in the study
- •2. History of difficulty swallowing, malabsorption, or other chronic gastrointestinal disease or conditions that may hamper compliance and/or absorption of the study intervention
- •3. Unstable cardiovascular function within 6 months prior to enrollment (i.e., ischemia, symptomatic angina, congestive heart failure, Class III to IV New York Heart Association uncontrolled conduction abnormalities including a history of long QTc syndrome [QTcF > 480 ms] and/or pacemaker, or myocardial infarction)
- •4. Hypertension uncontrolled by medication (i.e., systolic blood pressure = 150 mmHg and diastolic blood pressure = 90 mmHg)
- •5. History of other malignant disease within the past 5 years, other than successfully treated basal carcinoma of the skin or carcinoma in situ of the cervix
- •6. Known human immunodeficiency virus positivity, known active viral hepatitis, current alcohol abuse, or cirrhosis.
- •7. Ongoing active infection other than human immunodeficiency virus, hepatitis B virus, or hepatitis C virus, or treatment with a live attenuated vaccine within 4 weeks of dosing
- •Prior/Concomitant Therapy
- •8. Previous radiation therapy to the pelvis
- •9. Concurrent use of other anticancer therapy
- •10. Major surgical intervention within 4 weeks prior to the first dose of study intervention. Biopsy(s) to establish the diagnosis for rectal cancer is permitted. Diverting ostomy is permitted
- •11. Concomitant or prior use of medications or herbal supplements, known to be strong inhibitors of cytochrome P450 (CYP) 3A and/or CYP2C19, unless use can be discontinued 1 week prior to receiving the first dose of study intervention. Concomitant or prior use of medications or herbal supplements, known to be strong inducers of CYP3A and/or CYP2C19, unless use can be discontinued at least 3 weeks prior to receiving study
- •intervention. Concomitant or prior therapy use of medications or herbal supplements mainly metabolized by CYP3A with a narrow therapeutic index must be stopped at least 1 day prior to receiving study intervention
- •12. Concomitant use of H2-blocker or proton pump inhibitors (PPIs) (or unable to stop at least 5 days prior to the first treatment). Note that calcium carbonate is acceptable
- •13. Treatment with sorivudine or its chemically related analogues, such as brivudine
- •Prior/Concurrent Clinical Study Experience
- •14. Participation in any interventional clinical study within 28 days prior to Screening or during participation in this study
- •Diagnostic Assessments
- •15. Contraindications to MRI imaging
- •Other Exclusions
- •16. Pregnant or nursing (lactating) women
- •17. Known dihydropyrimidine dehydrogenase deficiency
- •18. History of severe and unexpected reactions to fluoropyrimidine therapy
- •19. Hypersensitivity to capecitabine or to any of the excipients or fluorouracil.
研究者
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