A Randomized Study Evaluating Tailoring of Advanced/Metastatic Colorectal Cancer (CRC) Therapy Using Circulating Cell-Free Tumor DNA (ctDNA) (TACT-D)
概览
- 阶段
- 2 期
- 干预措施
- Laboratory Procedure
- 疾病 / 适应症
- Refractory Colorectal Carcinoma
- 发起方
- M.D. Anderson Cancer Center
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Early change in circulating tumor-derived deoxyribonucleic acid (DNA) (ctDNA) as a predictor of radiographic progression (Arm II-SOC)
- 状态
- 进行中（未招募）
- 最后更新
- 3个月前
概览
简要总结
This phase II trial studies circulating cell-free tumor DNA testing to guide treatment with regorafenib or TAS-102 in patients with colorectal cancer that has spread to other areas of the body. Studying samples of blood from patients with colorectal cancer may help doctors understand how well patients respond to treatment. Regorafenib and TAS-102 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known how well ctDNA testing works in guiding treatment with regorafenib and TAS-102 for patients with advanced or metastatic colorectal cancer.
详细描述
PRIMARY OBJECTIVES: I. To evaluate the ability of early change in circulating tumor-derived deoxyribonucleic acid (ctDNA) (ctDNA-early dynamic changes \[EDC\] or A ctDNA) during systemic therapy in metastatic colorectal cancer (mCRC) to predict radiographic progression (only standard of care \[SOC\] arm). II. To evaluate differences in clinically significant treatment-related adverse events (TRAEs) of interest (grade 3/4 toxicity per National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, intolerable grade 2 toxicity or any toxicity requiring dose reduction) between SOC and ctDNA arm. SECONDARY OBJECTIVES: I. To evaluate differences in patient-reported outcomes (PROs) between SOC and ctDNA arm. II. To compare Response Evaluation Criteria in Solid Tumors (RECIST) duration of complete response (DCR) (partial response \[PR\] and stable disease \[SD\]) between SOC and ctDNA arm. III. To evaluate differences in overall survival (OS) between SOC and ctDNA arm. IV. To evaluate differences between SOC and ctDNA arm with regards to emergency severity indices (ESIs): Hospitalizations/emergency room visits. V. To evaluate differences between SOC and ctDNA arm with regards to ESIs: Need for medical interventions (blood transfusions and intravenous \[IV\] hydration). VI. To evaluate cost-effectiveness associated with both strategies, i.e. SOC strategy and ctDNA strategy in treatment of mCRC. VII. To compare time to deterioration of Eastern Cooperative Oncology Group (ECOG) performance status (PS) between SOC and ctDNA arms. VIII. To compare time to deterioration of PROs between SOC and ctDNA arms. IX. To evaluate differences in proportion of patients referred to clinical trial after completion of therapy between SOC and ctDNA arms. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients undergo ctDNA testing and depending on the results receive either regorafenib orally (PO) on days 1-21, trifluridine and tipiracil hydrochloride (TAS-102) PO twice daily (BID) on days 1-5 and 8-12, or regorafenib PO on days 1-21 and TAS-102 PO BID on days 1-5 and 8-12. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive regorafenib or TAS-102 per standard of care. Treatment continues in the event of disease stability or regression as per discretion of treating physician or absence of disease progression. After completion of study treatment, patients are followed up at 2 weeks and then monthly for up to 18 months.
研究者
入排标准
入选标准
- •Patients must have histologically or cytologically confirmed colorectal cancer.
- •Patients must have advanced or metastatic disease with no curative options.
- •Patients must have radiographically evaluable disease.
- •Patients must have had at least 2 prior therapies for mCRC (including fluorouracil \[5-FU\], oxaliplatin, irinotecan, bevacizumab; cetuximab/panitumumab \[for RAS wild type (WT) patients\]) and have either progressed on or intolerant to these agents or use of these agents is contraindicated.
- •Patients must be clinically eligible for either regorafenib or TAS-102 as per their treating physician.
- •Patients must have a negative serum pregnancy test done less than are equal to 14 days prior to randomization for women of childbearing potential only. Women of child bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry for the duration of study participation.
- •Patients must have ability to complete questionnaire(s) by themselves or with assistance.
- •Patients must have ability to provide informed written consent.
- •Patients must be willing to return to enrolling institution for follow-up as per study schedule.
- •Patients must be willing to provide blood samples for correlative studies.
排除标准
- •Patient who have received prior TAS-102 are eligible to enroll on the study if they can receive regorafenib and vice-versa. Otherwise these patients will be excluded from the study.
- •Congestive heart failure \> New York Heart Association (NYHA) class 2, unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months) or myocardial infarction less than 3 months prior to randomization.
- •Ongoing infection \> grade 2 CTCAE version 4.
- •Symptomatic metastatic brain or meningeal tumors unless the patient is \> 3 months from definitive therapy, has a negative imaging study within 4 weeks of randomization and is clinically stable with respect to brain lesions at the time of randomization (Note: patient must not be undergoing acute steroid therapy or taper \[chronic steroid therapy is acceptable provided that the dose is stable for one month prior to and following screening radiographic studies\]).
- •Renal failure requiring hematological or peritoneal dialysis.
- •Patients unable to swallow oral medications.
研究组 & 干预措施
Arm I (ctDNA testing, regorafenib, TAS-102)
Patients will receive either regorafenib by mouth on days 1-21 every 28 day cycle or TAS-102 by mouth twice daily on days 1-5 and 8-12 every 28 day cycle. Patients in this arm will get ctDNA testing and will continue treatment beyond 1st cycle depending on ctDNA results. Beyond that patients will continue treatment in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Procedure
Arm I (ctDNA testing, regorafenib, TAS-102)
Patients will receive either regorafenib by mouth on days 1-21 every 28 day cycle or TAS-102 by mouth twice daily on days 1-5 and 8-12 every 28 day cycle. Patients in this arm will get ctDNA testing and will continue treatment beyond 1st cycle depending on ctDNA results. Beyond that patients will continue treatment in the absence of disease progression or unacceptable toxicity.
干预措施: Quality-of-Life Assessment
Arm I (ctDNA testing, regorafenib, TAS-102)
Patients will receive either regorafenib by mouth on days 1-21 every 28 day cycle or TAS-102 by mouth twice daily on days 1-5 and 8-12 every 28 day cycle. Patients in this arm will get ctDNA testing and will continue treatment beyond 1st cycle depending on ctDNA results. Beyond that patients will continue treatment in the absence of disease progression or unacceptable toxicity.
干预措施: Questionnaire Administration
Arm I (ctDNA testing, regorafenib, TAS-102)
Patients will receive either regorafenib by mouth on days 1-21 every 28 day cycle or TAS-102 by mouth twice daily on days 1-5 and 8-12 every 28 day cycle. Patients in this arm will get ctDNA testing and will continue treatment beyond 1st cycle depending on ctDNA results. Beyond that patients will continue treatment in the absence of disease progression or unacceptable toxicity.
干预措施: Regorafenib
Arm I (ctDNA testing, regorafenib, TAS-102)
Patients will receive either regorafenib by mouth on days 1-21 every 28 day cycle or TAS-102 by mouth twice daily on days 1-5 and 8-12 every 28 day cycle. Patients in this arm will get ctDNA testing and will continue treatment beyond 1st cycle depending on ctDNA results. Beyond that patients will continue treatment in the absence of disease progression or unacceptable toxicity.
干预措施: Trifluridine and Tipiracil Hydrochloride
Arm II (SOC)
Patients will receive either regorafenib by mouth on days 1-21 every 28 day cycle or TAS-102 by mouth twice daily on days 1-5 and 8-12 every 28 day cycle as per standard of care. Patients in this arm will continue treatment in the absence of disease progression or unacceptable toxicity.
干预措施: Best Practice
Arm II (SOC)
Patients will receive either regorafenib by mouth on days 1-21 every 28 day cycle or TAS-102 by mouth twice daily on days 1-5 and 8-12 every 28 day cycle as per standard of care. Patients in this arm will continue treatment in the absence of disease progression or unacceptable toxicity.
干预措施: Quality-of-Life Assessment
Arm II (SOC)
Patients will receive either regorafenib by mouth on days 1-21 every 28 day cycle or TAS-102 by mouth twice daily on days 1-5 and 8-12 every 28 day cycle as per standard of care. Patients in this arm will continue treatment in the absence of disease progression or unacceptable toxicity.
干预措施: Questionnaire Administration
Arm II (SOC)
Patients will receive either regorafenib by mouth on days 1-21 every 28 day cycle or TAS-102 by mouth twice daily on days 1-5 and 8-12 every 28 day cycle as per standard of care. Patients in this arm will continue treatment in the absence of disease progression or unacceptable toxicity.
干预措施: Regorafenib
Arm II (SOC)
Patients will receive either regorafenib by mouth on days 1-21 every 28 day cycle or TAS-102 by mouth twice daily on days 1-5 and 8-12 every 28 day cycle as per standard of care. Patients in this arm will continue treatment in the absence of disease progression or unacceptable toxicity.
干预措施: Trifluridine and Tipiracil Hydrochloride
结局指标
主要结局
Early change in circulating tumor-derived deoxyribonucleic acid (DNA) (ctDNA) as a predictor of radiographic progression (Arm II-SOC)
时间窗: First 4 months after treatment initiation
Number of patients with rise in ctDNA level will be compared to Number of patients with progression of disease on scans.
Treatment-related adverse events (TRAEs) of interest (grade 3/4 toxicity, intolerable grade 2 toxicity, or any toxicity requiring dose reduction) between arms
时间窗: First 4 months after treatment initiation
Will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. To compare the proportions of patients who have experienced TRAEs of interest within the first 4 months between the two treatment arms, Fisher's exact test will be used.
次要结局
- Mean patient-reported outcomes (PROs) score as per PRO-CTCAE(Up to 18 months)
- Overall survival (OS)(Up to 18 months)
- Percentage of patients who present with events of special interest (ESIs)(Up to 18 months)
- Cost measured in US dollars(Up to 18 months)
- Median time to performance status deterioration(Up to 18 months)
- Proportion of patients referred to clinical trial(Up to 18 months)
- Mean patient-reported outcomes (PROs) score as per MD Anderson Symptom Inventory (MDASI-GI)(Up to 18 months)
- Percentage of patients with partial response (PR)(Up to 18 months)
- Percentage of patients with stable disease (SD)(Up to 18 months)
- Median time to PRO deterioration(Up to 18 months)