EUCTR2015-004467-36-GB进行中（未招募）1 期
A Phase 1/2 Trial of Oral SRA737 (a Chk1 Inhibitor) Given in Combination with Gemcitabine plus Cisplatin or Gemcitabine Alone in Subjects with Advanced Cancer
适应症
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 140
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
- •Dose-Escalation and Cohort Expansion:
- •1) Written, signed, and dated informed consent
- •2) In the Dose Escalation Phase, subjects with a locally advanced or metastatic, histologically or cytologically proven solid tumor, relapsed
- •after or progressing despite conventional treatment for which no conventional therapy is considered appropriate by the investigator or is
- •declined by the subject
- •3) Life expectancy: at least 12 weeks
- •4) World Health Organization performance status: 0-1
- •5) Hematological and biochemical indices within the ranges shown below, measured within 1 week prior to the subject receiving their first
- •dose of SAR737 (or gemcitabine if the SRA737 dose for PK is omitted)
- •Hemoglobin - = 90 g/L
- •Absolute neutrophil count - = 1.5 × 10^9/L
- •Platelet count - = 100 × 10^9/L
- •Bilirubin - = 1.5 × upper limit of normal (ULN) unless due to Gilbert's syndrome in which case up to 3 × ULN is permissible
- •Alanine aminotransferase and aspartate aminotransferase and Alkaline Phosphatase - = 2.5 × ULN unless raised due to tumor in which case up
- •to 5 × ULN is permissible
- •Serum Creatinine - = 1.5 × ULN
- •Electrolytes: magnesium, potassium and calcium - If electrolyte levels are low, it must be demonstrated that they can be normalized and
- •maintained using supplements prior to the subject beginning study treatment. Supplement use should continue while on study as
- •appropriate
- •6) Subjects who are 18 years or older
- •7) Subjects must have archival tumor tissue available for tumor profiling OR accessible tumor and willingness to consent to a biopsy for the
- •collection of tumor tissue
- •Cohort Expansion:
- •8) Subjects in the indication specific cohort expansion must have histologically or cytologically proven advanced malignancy of the types
- •specified in Inclusion Criterion 11
- •9) Have measurable disease according to Response Evaluation Criteria in Solid Tumors, Version 1.1
- •10) Subjects must have predicted sensitivity to Chk1 inhibition
- •a. For subjects with HGSOC, documented somatic or germline BRCA1 and BRCA2 wild-type status will confer eligibility without requirement for
- •prospective genetic profiling. If documented BRCA status is not available, genetic profiling may be performed prospectively to determine
- •eligibility
- •b. Subjects with SCLC are eligible without requirement for prospective genetic profiling on the basis of very high prevalence of cancer related
- •alterations in the tumor suppressor genes (eg, TP53 and RB1) in this population.
- •c. For subjects with STS, and any others for whom genetic profiling is performed prospectively, eligibility will be determined by the sponsor's
- •review of genetic abnormalities detected in genes in the following categories:
- •a) Key tumor suppressor genes regulating G1 cell cycle progression/arrest such as RB1, TP53, etc. For relevant cancers, positive
- •human papilloma virus (HPV) status is also considered for eligibility.
- •b) The DNA damage response pathway including ATM, BRCA1, BRCA2, mismatch repair genetic alterations and/or high microsatellite instability
- •c) Genetic indicators of replicative stress such as gain of function/amplification of Chk1 or ATR or other related gene
- •d) Oncogenic drivers such as MYC, CCNE1, etc.
- •d. For subjects with anogenital cancer, known HPV positive status will confer eligibility without requirement for prospective genetic profiling. If
- •HPV status is not known or not positive, genetic profiling (or HPV testing where appropriate) may be performed
排除标准
- •1. Have received prior or current anticancer therapy within the noted time periods prior to receiving SRA737 or have recovered from toxicity consistent with exclusion criterion 5:
- •a) Radiotherapy (except for symptom control and where the lesions will not be used as measurable disease), chemotherapy, therapy with poly ADP ribose polymerase (PARP) inhibitors, other targeted therapies, or other IMPs within 2 weeks
- •b) Nitrosoureas or Mitomycin C within 6 weeks
- •c) Any prior treatment with a Chk1 inhibitor, or prior treatment with an ATR inhibitor within 6 months.
- •2) No more than 3 previous treatment regimens for advanced disease (not applicable to HGSOC expansion cohort), unless otherwise approved by sponsor. Prior gemcitabine therapy is permitted as previous therapy.
- •3) Other malignancies within the past 2 years with the exception of adequately treated tumors that are associated with an expected 5 year disease-free survival of = 95%.
- •4) If, in the opinion of the investigator, the subject is highly likely to experience clinically significant myelosuppression, based on previous experience with chemotherapy.
- •5) Ongoing toxic manifestations of previous treatments greater than National Cancer Institute – Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade 1. Exceptions to this are alopecia or certain toxicities, which in the opinion of the investigator and the sponsor’s Medical Monitor should not exclude the subject.
- •6) History of allergy to gemcitabine.
- •7) New or progressing brain metastases. Subjects with brain metastases that have been asymptomatic and radiologically stable over an 8-week period and have not been treated with steriods during that time may be included with approval from the sponsor.
- •8) Women of childbearing potential (WOCBP) or women who are already pregnant or lactating. However, those subjects who have a negative serum or urine pregnancy test before enrollment and agree to use 2 forms of contraception or agree to sexual abstinence, effective from the first administration of SRA737, throughout the trial and for 6 months afterwards are considered eligible.
- •9) Male subjects with partners of child bearing potential, unless they agree to take measures not to father children by using a barrier method of contraception defined, effective from the first administration of SRA737 through the trial and for 6 months after their final SRA737 dose. Men with pregnant or lactating partners must be advised to use barrier method contraception (eg, condom plus spermicidal gel) to prevent exposure of the fetus or neonate.
- •10) Major surgery from which the subject has not yet recovered.
- •11) At high medical risk because of nonmalignant systemic disease including active uncontrolled infection.
- •12) Known to be serologically positive for hepatitis B, hepatitis C or human immunodeficiency virus.
- •13) Serious cardiac condition, such as concurrent congestive heart failure, prior history of class III/ IV cardiac disease (New York Heart Association [NYHA]), left ventricular ejection fraction < 45% at baseline, history of cardiac ischemia within the past 6 months, or prior history of cardiac arrhythmia requiring treatment, unless approved by the sponsor.
- •14) Prior bone marrow transplant or have had extensive radiotherapy to greater than 25% of bone marrow within the previous 8 weeks.
- •15) Peanut allergy (unless this restriction is removed by the sponsor).
- •16) QTcF > 450 msec in adult mal
研究者
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