A Single Arm Phase 2 Trial With a Safety Lead in Evaluating the Addition of OK-1 to Weekly Paclitaxel in Patients With Recurrent Endometrial Cancer
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 66
- 试验地点
- 1
- 主要终点
- Number and Proportion of Patients Who Safely Tolerate The Combination of OK-1 and Paclitaxel
研究概览
简要总结
The purpose of this study is to evaluate whether treatment with the investigational drug OK-1 in combination with paclitaxel can reduce tumor burden in patients with advanced or recurrent endometrial cancer (A/R-EC).
详细描述
Participants will receive OK-1 capsules by mouth twice daily in continuous 21-day treatment cycles. Paclitaxel will be administered by intravenous (IV) infusion once weekly during each 21-day cycle. A combined total of 66 patients will participate in this study, with the initial safety lead-in cohort involving 30 patients, followed by 36 new patients enrolled in the phase 2 arm.
Treatment cycles will continue until the participant, the treating physician, or the study team determines that continued participation is no longer appropriate due to disease progression, unacceptable side effects, withdrawal of consent, or another clinical reason. Throughout the study, participants will undergo regular laboratory testing and clinical examinations to monitor their health and treatment response. Participation in the study is expected to last for up to one year.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •At least 18 years-of-age at the time of signature of the informed consent form (ICF).
- •Histologically documented carcinoma of the endometrium, including endometrioid, serous, mixed adenocarcinoma, clear-cell carcinoma, or carcinosarcoma. Evidence that the endometrial cancer is advanced, recurrent, or persistent and has relapsed, or is refractory to curative therapy or established treatments.
- •Must have pre-treatment archival tissue.
- •Measurable disease by RECIST v1.1 is required for the phase 2 portion of the study. Patients with accessible disease are eligible for the safety lead in cohorts. Patients with biochemical recurrent disease only (ie Ca125 elevation or ctDNA elevation in absence of visible disease on CT scan are NOT eligible)
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
- •Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
- •Adequate organ function, defined in study protocol.
- •Prior therapy: Patients must have received ≥1 platinum-based therapy in the recurrent/metastatic setting and not more than 5 prior lines of therapies.
- •Adjuvant therapy given for early stage, high risk endometrial cancer does NOT count as the line of qualifying platinum based chemotherapy unless disease recurrence is documented < 12 months from completion. If >12 months has elapsed, patients should receive another line of platinum based chemotherapy.
- •Maintenance therapy (e.g., bevacizumab, poly adenosine diphosphate-ribose polymerase [PARP] inhibitor, endocrine therapy or immune checkpoint inhibitor will be considered part of the preceding line of therapy.
- •Therapy changed due to toxicity in the absence of progression will be considered part of the same line (i.e., not counted independently)
- •Hormonal therapy will not be counted as a separate line of therapy.
- •Patients should have received an immune checkpoint inhibitor as part of a prior line of therapy unless contraindicated to participate in this trial.
- •If the Patient has a tumor that is HER2 3+, trastuzumab deruxtecan should have been used unless ineligible.
- •During the course of this clinical trial, if an antibody drug conjugate becomes available therapy for recurrent endometrial cancer, patients should be treated with that therapy unless ineligible
- •The patient must provide study-specific informed consent prior to study entry and, for patients treated in the U.S., authorization permitting release of personal health information.
- •QTcF < 470 msec
排除标准
- •Patients who have received prior weekly paclitaxel for recurrent endometrial cancer.
- •Major surgical procedure within 28 days prior to registration, or anticipation of need for major surgical procedure during the study. Note: Placement of a vascular access device, thoracentesis, and/or paracentesis will not be considered major surgery.
- •Women who are pregnant or are unwilling to discontinue nursing.
- •Evidence of bleeding diathesis or clinically significant coagulopathy within the past 3 months. Patients are not excluded for past or current use of anticoagulation.
- •There is no prespecified washout from prior therapies.
- •Patients with adverse events related to prior therapies must have resolution to < grade
- •Patients with ≤ Grade 2 neuropathy or ≤ Grade 2 alopecia are an exception to this criterion and may qualify for the study. Note: Grade 2 neuropathy is neuropathy on one medication so patients may be eligible following discussions with the medical monitor.
- •Additional exceptions include immune-related AEs such as adrenal insufficiency, hypothyroidism (controlled), endocrine-related toxicities due to checkpoint inhibitor treatment (can be corrected through hormone replacement therapy) and Grade 2 laboratory abnormalities that meet the eligibility requirements.
- •Patients currently taking and unwilling/unable to discontinue the use of drugs that are known to be strong/moderate inhibitors or inducers of CYP3A4, CYP2C8, CYP2C19, and CYP2C
- •(Refer to Appendix III)
- •Comorbid Conditions: No active infection requiring parental antibiotics except for urinary tract infection.
- •No evidence of intra-abdominal abscess, abdominal/pelvic fistula, gastrointestinal perforation, or GI obstruction requiring gastrostomy tube. NOTE: required interval since last bowel obstruction: 30-day minimum for incomplete obstruction, resolved with conservative means; 6 months for fistula. Patients with a history of a large bowel obstruction that has been successfully diverted and do not meet the criteria for small bowel obstruction are eligible.
- •Patients with risk factors for torsade de pointes (TdP) such as clinically significant heart failure (defined as a known ejection fraction < 50%), uncorrected grade 2 or greater hypokalemia, family history of long QT syndrome )
结局指标
主要结局
Number and Proportion of Patients Who Safely Tolerate The Combination of OK-1 and Paclitaxel
时间窗: 12 Months
Quantitative assessment of patients who experienced \>gr.3 AEs during OK-1 in combination with a weekly paclitaxel regimen using CTCAE v6
Proportion of Patients Who Successfully Completed The Safety Lead-In Phase and Tolerated OK-1 In Combination With Paclitaxel.
时间窗: 1 Year
Completion of safety lead-in with an established phase 2 dose for OK-1 combination with weekly intravenous paclitaxel
Proportion of Participants Overrall Response Rate To OK-1 In Comination With Paclitaxel
时间窗: 2 Years
To quantitatively evaluate the overall response rate (ORR) in the Phase 2 cohort by determining the proportion of participants who achieve a complete response (CR) or partial response (PR) to treatment.
次要结局
- Participants Duration of Response To OK-1 In Combination With Paclitaxel(2 years)
- Assess Progression Free Survival In Participants Who Tolerated OK-1 In Combination With Paclitaxel(2 years)
- Overall Survival at 12 Months(2 Years)