KCT0003466已完成未知
Phase1b/2 study of AZD8186 in combination with paclitaxel in patients with advanced gastric cancer
试验速览
- 阶段
- 未知
- 状态
- 已完成
- 入组人数
- 28
研究概览
简要总结
In phase Ib (n=10), both MTD and RP2D were determined at paclitaxel 80 mg/m2 and AZD8186 120 mg BID. In phase II, 18 patients were enrolled [PTEN loss (n = 18) and PIK3CB mutation (n = 1)]. The 4-month PFS rate was 18.8% (3 of 16 evaluable patients) and further enrollment stopped due to futility. Although the combination of AZD8186 and paclitaxel was well tolerated, limited clinical efficacy was observed.
研究设计
- 研究类型
- Interventional Study
入排标准
- 年龄范围
- 19(Year) 至 o Limit（—）
- 性别
- All
入选标准
- •1. Have the willingness to sign a written informed consent document prior to any study specific procedures
- •2. Age > 19 years of male and female
- •3. At each phase of the trial, subjects who meet the following requirements in the appropriate phase will be enrolled.
- •A. Phase 1b: Subjects with a histologically confirmed metastatic solid tumor that have progressed after treatment with approved therapies or for which there is no standard effective therapy available.
- •B. Phase 2b: Subjects with histologically confirmed locally advanced or metastatic gastric cancer that have progressed after treatment with first-line fluoropyrimidine-based chemotherapy, with PTEN loss by IHC (immunohistochemistry), PTEN gene abnormality (PTEN gene deletion or loss of function mutation) or PIK3CB gene abnormality (amplification or gain of function mutation) identified by local CLIA certified next generation sequencing (NGS). If the subject received adjuvant chemotherapy after curative gastric resection and lymph node dissection, adjuvant chemotherapy is considered to be the first-line palliative chemotherapy if the disease recurred during adjuvant chemotherapy or within 6 months after the completion of adjuvant chemotherapy.
- •4. Patients must have measurable disease based on RECIST 1.1 (Phase 2 part only). Measurable disease will not be required for enrollment in the phase1b part. Patients with evaluable lesion only (without measurable lesion) can be enrolled in the phase 1b part.
- •5. ECOG performance status 0-1
- •6. Patients must have adequate organ and marrow function
- •7. Adequate cardiac function
- •8. Patients must be able to swallow and retain oral medications
- •9. Serum ß-HCG test negative within 14 days before the first administration (women of childbearing potential only).
- •10. Requirement for contraception
排除标准
- •Subjects with any of the following criteria are excluded from this study:
- •1. Active central nervous system (CNS) lesions (i.e., those with radiologically unstable or symptomatic brain lesions). For those who receive radiation or surgical treatment, the subject can be enrolled if the subject is maintained without evidence of CNS disease progression for more than 4 weeks. However, patients with a leptomeningeal metastases are excluded.
- •2. Treatment with any of the following:
- •Nitrosourea or mitomycin C within 6 weeks of the first dose of study treatment
- •Any cytotoxic chemotherapy from a previous treatment regimen within 14 days. If the subject received an investigational drug from another clinical trial, the subject can be enrolled after 2 weeks of last administration and more than 5 x half–life of the investigational drug. If monoclonal antibody therapy was given, the subject can be enrolled after four weeks after the last does.
- •Strong or moderate inducers or inhibitors of CYP3A4 within 2 weeks before the first dose of study treatment
- •Radiotherapy with a wide field of radiation within 4 weeks or radiotherapy with a limited field of radiation for palliation within 2 weeks of the first dose of study treatment. If acute symptoms of radiation have fully resolved, the extent and timing of radiotherapy for eligibility can be discussed between the local investigator and principal investigator.
- •Any previous exposure to a PI3 kinase inhibitor (including selective or pan PI3K inhibitors), AKT, mTOR inhibitors.
- •3. History of allogeneic bone marrow transplantation or organ transplantation
- •4. History of another primary cancer (excluding gastric cancer):
- •Exceptions are:
- •Adequately treated non-melanoma skin cancer (basal cell or squamous cell carcinoma), curatively treated in situ cancer of the cervix, completely resected thyroid cancer without distant metastasis in which all treatment has been completed (Appropriate wound healing is required prior to clinical trial enrollment)
- •Other curatively treated solid tumors except for gastric cancer with no evidence of disease recurrence at least 36 months before participating in this trial
- •5. Clinically significant cardiovascular disease
- •6. Persistent uncontrolled hypertension
- •7. Seropositivity of HIV, or known active hepatitis B and/or active hepatitis C infection.
- •8. Impairment of gastrointestinal function or gastrointestinal disorders (e.g. untreated ulcerative disorders; uncontrolled nausea, vomiting, or diarrhea; absorption disorder syndrome; small bowel resection; ileostomy). Patients with ileostomy will not be allowed to be enrolled, but patients with colostomy can be enrolled to this study.
- •9. As judged by the Investigator, all other symptoms and associated disease for which the investigator determined that participation in this study is contraindicated
- •10. Pregnant or lactating women.
- •11. Medical, psychiatric, cognitive, or other conditions that may interfere with the ability of the subject to understand the subject information, provide the informed consent, follow the protocol process, or complete the clinical trial
- •12. Hypersensitivity to paclitaxel
研究者
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