Phase IIA Trial of Delayed Initiation of Olaparib Maintenance Therapy in Platinum Sensitive Recurrent Ovarian Cancer
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- Time to Next Therapy
研究概览
简要总结
The purpose of this study is to test if delaying the start of the olaparib until there is a rise in a tumor marker called CA-125 will result in a longer time until the next or different treatment for the patient's cancer. The study will also evaluate how delaying the start of maintenance therapy will affect symptoms; physical functioning; quality of life; and impact on finances.
详细描述
This is a Phase II trial will investigate if waiting until the time of chemical recurrence, denoted by rising CA125, to start a PARP inhibitor will lead to an improved time to next therapy with improved quality of life and at a lower financial toxicity.
PARP-I have shown efficacy as both monotherapy and as maintenance therapy. This trial will explore whether patients with recurrent ovarian cancer could derive the same efficacy benefit from a delayed start of a PARP-I compared to immediate maintenance therapy. Delayed start would have the benefit of sparing the physical, psychological, and financial toxicity associated with prolonged treatment. This approach would be particularly relevant in a population of platinum-sensitive patients who can have prolonged treatment-free intervals.
With widespread use of PARP-I, regardless of timing, understanding, and overcoming PARP-I resistance is becoming a major clinical need.
Enrollment will start within 8 weeks of completion of platinum-based treatment. Monitored with CA 125 levels every 28 days. Olaparib will be started when CA 125 rises by two-fold of their nadir value. Olaparib will be dosed at 300 mg orally twice a day, 28 days of treatment will be a cycle. Follow-up will consist of CA125 drawn every 28 days and CT scans obtained at doubling of CA- 125 and then every 12 weeks* to assess for recurrence or progression. Clinician- and patient-reported adverse events recorded every 28 days. Cancer-related worry and distress assessed every 28 days. Measures of quality of life and physical function, and financial toxicity assessed every 12 weeks.
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
- •Patient has platinum-sensitive, recurrent ovarian, fallopian-tube or peritoneal cancer. Platinum sensitivity is defined as complete clinical remission after frontline chemotherapy lasting greater than 6 months
- •Patient has completed at least 2 courses of platinum-based chemotherapy with a PR or CR as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.139 or a CA-125 response, according to Gynecological Cancer InterGroup (GCIG) criteria40
- •BRCA testing required (results not needed for registration)
- •ECOG performance status score of 0, 1, or 2 (See Appendix A)
- •Life expectancy greater than 6 months
- •Normal organ and marrow function as defined: Absolute neutrophil count (ANC) ≥ 1.5 x 109/L; Platelets ≥ 100 x 109/L; Hemoglobin (Hgb) ≥ 8 g/dL (blood transfusions to reach this amount are allowed); Serum creatinine ≤ 1.5 mg/dL; Total serum bilirubin ≤ 1.5 x ULN; AST and ALT ≤ 2.5 x ULN
- •Able to take oral medication
- •Not pregnant and not breastfeeding
- •Able to understand and willingness to sign a written informed consent document
- •Patients must be enrolled within 8 weeks of completing last cycle of chemotherapy
排除标准
- •Patient has had a prior invasive malignancy diagnosed within the last five years (except [1] non-melanoma skin cancer or [2] prior in situ carcinoma of the cervix or breast [3] has been without evidence of invasive disease for greater than 3 years)
- •Patients receiving any other investigational agents
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to olaparib
- •Uncontrolled intercurrent illness that could affect their participation in the study including, but not limited to, ongoing or active infection; symptomatic congestive heart failure; unstable angina pectoris; cardiac arrhythmia; known inadequately controlled hypertension; significant pulmonary disease including dyspnea at rest, patients requiring supplemental oxygen, or poor pulmonary reserve; or psychiatric illness/social situations that would limit compliance with study requirements
- •Impairment of gastrointestinal function or disease that may significantly alter the absorption of olaparib
- •Patients who have received prior treatment with a PARP inhibitor
- •History of noncompliance to medical regimens
研究组 & 干预措施
Olaparib
Olaparib dosed at 300mg orally twice daily, started when CA125 rises by two-fold of nadir value.
干预措施: Olaparib (Drug)
结局指标
主要结局
Time to Next Therapy
时间窗: Up to 35 months
The time to next therapy from completion of platinum-based therapy for treatment of recurrence until initiation of post-olaparib treatment.
次要结局
- The Functional Assessment of Cancer Therapy + Ovarian-specific Scale (FACT-O)(Up to 37 months)
- Progression-free Survival (PFS)(Up to 35 months)
- Overall Survival (OS)(Up to 35 months)
- Overall Response Rate (ORR)(Up to 35 months)
- PROMIS Physical Function-20a(Up to 35 months)
- Modified Collection of Indirect and Non-medical Direct Costs (COIN)(Up to 35 months)
- Adverse Events Possibly, Probably or Definitely Related to Treatment(Up to 35 months)
- Assessment of Survivor Concerns (ASC) Worry Subscale and Impact of Event Scale (IES-R)(Up to 35 months)
研究者
Sarah E Taylor
Assistant Professor of Medicine
University of Pittsburgh