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.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03844620.
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):
IVa. Hospitalizations/emergency room visits.
IVb. Need for medical interventions (blood transfusions and intravenous [IV] hydration).
V. To evaluate cost-effectiveness associated with both strategies, i.e. SOC strategy and ctDNA strategy in treatment of mCRC.
VI. To compare time to deterioration of Eastern Cooperative Oncology Group (ECOG) performance status (PS) between SOC and ctDNA arms.
VII. To compare time to deterioration of PROs between SOC and ctDNA arms.
VIII. 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.
Lead OrganizationM D Anderson Cancer Center
Principal InvestigatorKanwal Pratap Singh Raghav
