The following clinical trials represent a selection of key studies currently recruiting patients with colorectal cancer for inclusion in investigations of new therapies and new regimens of existing treatments for the disease. Each clinical trial description includes the NLM Identifier to be used as a reference with ClinicalTrials.gov. This information can help oncology practice managers and providers direct eligible patients to one of these clinical trials.
1 Encorafenib plus Cetuximab with or without Chemotherapy in Previously Untreated BRAFV600E Mutation–Positive Metastatic CRC
The purpose of this open-label, multicenter, randomized phase 3 study is to compare the efficacy of encorafenib (Braftovi) plus cetuximab (Erbitux), alone or in combination with chemotherapy, with current standard-of-care therapy in patients with previously untreated BRAFV600E mutation–positive metastatic colorectal cancer (CRC). Patients aged ≥16 years with histologically or cytologically confirmed stage IV CRC with BRAFV600E mutation, who have measurable or evaluable disease, who have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and who have received previous adjuvant or neoadjuvant therapy that resulted in relapse or metastasis <6 months after completion, may be eligible if other criteria are met. A safety lead-in portion of the study will evaluate the tolerability and pharmacokinetics of encorafenib plus cetuximab in combination with modified FOLFOX6 (mFOLFOX6; 5-fluorouracil [5-FU], leucovorin, and oxaliplatin [Eloxatin]) or FOLFIRI (5-FU, leucovorin, and irinotecan [Camptosar]) in separate cohorts to identify the chemotherapy combination to be used in the phase 3 portion. Eligible patients will be randomized to receive either encorafenib 300 mg orally (PO) once daily plus intravenous (IV) cetuximab 500 mg/m2 every 2 weeks alone or in combination with mFOLFOX6 or FOLFIRI, or standard chemotherapy treatment.
The primary outcome measures are incidence of dose-limiting toxicities in the safety lead-in study after 1 completed cycle, and progression-free survival (PFS) in the phase 3 study, from date of randomization to earliest documented disease progression or death due to any cause. Secondary outcome measures in the safety lead-in study are the incidences of adverse events (AEs); abnormal clinical laboratory parameters, vital signs, and electrocardiograms; dose interruptions, modifications, and discontinuations due to AEs; and overall survival (OS), PFS, and duration of response (DOR) by investigator. Secondary outcome measures in the phase 3 study are OS, overall response rate (ORR), DOR, PFS, incidence of AEs, and change from baseline in the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC-QLQ-C30) score. The study plans to enroll 930 participants throughout the United States and worldwide. For more information, contact the Pfizer CT.gov Call Center at 1-800-718-1021 or
2 Fruquintinib plus Best Supportive Care versus Best Supportive Care Alone in Refractory Metastatic CRC
The purpose of this global, randomized, double-blind, placebo-controlled, multicenter, phase 3 clinical trial is to compare the efficacy and safety of fruquintinib (Elunate), a vascular endothelial growth factor receptor inhibitor, in combination with best supportive care (BSC) versus placebo plus BSC in patients with advanced CRC who have disease progression on or intolerance to chemotherapy, biologics, and TAS-102 (trifluridine/tipiracil; Lonsurf) or regorafenib (Stivarga). Patients aged ≥18 years with histologically and/or cytologically documented metastatic CRC, whose disease has progressed on or been intolerant to treatment with either TAS-102 or regorafenib, who have received treatment with immune checkpoint inhibitors if their tumors are microsatellite-high (MSI-H) or mismatch repair deficient (dMMR), who have metastatic disease >6 months after receiving adjuvant oxaliplatin (Eloxatin), and who have measurable disease according to RECIST v1.1 and an ECOG performance status of 0 to 1 may be eligible if other criteria are met. Eligible patients will be randomized to receive fruquintinib plus BSC or placebo plus BSC.
The primary outcome measure is to evaluate the OS of fruquintinib plus BSC compared with placebo plus BSC in patients with refractory metastatic CRC for up to 10 years. The study plans to enroll 687 participants throughout the United States and worldwide. For more information, contact Alberto Fernandez at 1-973-567-3891 or
3 Nivolumab Alone or in Combination with Ipilimumab versus Chemotherapy in Treatment of dMMR/MSI-H Metastatic CRC
The purpose of this randomized, phase 3 study is to compare the clinical benefit of nivolumab (Opdivo) monotherapy, nivolumab plus ipilimumab (Yervoy), or chemotherapy in patients with dMMR/MSI-H metastatic CRC. Patients aged ≥18 years with histologically confirmed recurrent or metastatic CRC irrespective of previous treatment history, or no previous treatment history, with chemotherapy and/or targeted agents not amenable to surgery, who have known tumor dMMR or MSI-H status per local standard practice, and who have an ECOG performance status ≤1 may be eligible if other criteria are met. Eligible patients will be randomized to receive either nivolumab monotherapy, nivolumab plus ipilimumab, or investigator’s choice chemotherapy (with the option to receive nivolumab plus ipilimumab treatment if disease progresses).
The primary outcome measure is PFS by blinded independent central review (BICR), up to 5 years. Secondary outcome measures are ORR, OS, and PFS by investigator and BICR, respectively, as comparison in all arms, for up to 5 years. The study plans to enroll 748 participants throughout the United States and worldwide. For more information, contact the recruiting sites directly with the first line of the e-mail including the NCT number and site number. If there is no contact information for the recruiting site, e-mail
4 Adagrasib plus Cetuximab versus Chemotherapy as Second-Line Treatment in Advanced CRC with KRASG12C Mutation
The purpose of this open-label, randomized phase 3 study is to evaluate the efficacy of adagrasib (MRTX849) plus cetuximab (Erbitux) versus chemotherapy as second-line treatment in patients with advanced CRC and KRASG12C mutation whose disease progressed on or after standard first-line therapy. Patients aged ≥18 years with histologically confirmed diagnosis of colorectal carcinoma with KRASG12C mutation in tumor tissue, and who had previously received first-line treatment for advanced CRC with fluoropyrimidine-based chemotherapy regimen containing either oxaliplatin (Eloxatin) or irinotecan (Camptosar) and have radiographically documented progression of disease on or after treatment may be eligible if other criteria are met. Eligible patients will be randomized to receive either adagrasib plus cetuximab in 28-day cycles or chemotherapy (FOLFIRI or mFOLFOX6 regimens).
The primary outcome measures are OS and PFS, defined as date of randomization to date of death due to any cause and time from randomization until disease progression or death from any cause, whichever comes first, respectively. Secondary outcome measures include the number of patients with treatment-emergent AEs, objective response rate, DOR, patient-reported outcomes as assessed by EORTC-QLQ-C30, and quality-of-life assessment as assessed by EuroQol Quality of Life 5-Dimensional Questionnaire. The study plans to enroll 420 participants throughout the United States and Puerto Rico. For more information, contact Mirati Therapeutics Study Locator Services at 1-844-893-5530 or
5 Trifluridine-Tipiracil plus Bevacizumab versus Trifluridine-Tipiracil Monotherapy in Refractory Metastatic CRC
The purpose of this international, open-label, 2-arm, controlled, randomized phase 3 study is to evaluate the efficacy and safety of trifluridine-tipiracil (Lonsurf) in combination with bevacizumab (Avastin) versus trifluridine-tipiracil monotherapy in patients with refractory metastatic CRC. Patients aged ≥18 years with histologically confirmed unresectable adenocarcinoma of the colon or rectum, with previously determined RAS mutation–positive or wild-type, who have received ≥2 previous chemotherapy regimens and had disease progression or intolerance to their last regimen, and who have an ECOG performance status of 0 or 1 may be eligible if other criteria are met. Eligible patients will be randomized to receive either trifluridine-tipiracil PO twice daily on a 5-day-on and 2-day-off schedule for 2 weeks, followed by a 14-day rest plus bevacizumab every 2 weeks on days 1 and 15, or trifluridine-tipiracil alone.
The primary outcome measure is OS, defined as the observed time elapsed between the date of randomization and the date of death due to any cause. Secondary outcome measures include PFS, ORR, disease control rate, treatment-emergent AEs as assessed by Common Technology Criteria for Adverse Events v5.0, and EORTC-QLQ-C30 and EuroQol Quality of Life 5-Dimensional Questionnaire. The study plans to enroll 490 participants throughout the United States and worldwide. For more information, contact Karim Benhadji, MD, at 1-609-250-7336 or e-mail
6 Olaparib with or without Bevacizumab versus Bevacizumab plus a Fluoropyrimidine in Unresectable or Metastatic CRC
The purpose of this open-label, parallel, randomized phase 3 study is to evaluate the efficacy and safety of olaparib (Lynparza) alone or in combination with bevacizumab (Mvasi) versus bevacizumab plus a fluoropyrimidine (5-FU or capecitabine [Xeloda]) as treatment in patients with unresectable or metastatic CRC whose disease has not progressed following first-line induction. Patients aged ≥18 years with histologically confirmed metastatic or unresectable stage IV colorectal adenocarcinoma whose disease has not progressed after receiving a first-line induction course of ≥6 cycles of FOLFOX plus bevacizumab or 4 cycles of CAPOX (capecitabine plus oxaliplatin) plus bevacizumab as first-line therapy, who required discontinuation of oxaliplatin due to unacceptable toxicity, and who have an ECOG performance status of 0 to 1 within 10 days before randomization may be eligible if other criteria are met. Eligible patients will be randomized to receive olaparib 300 mg PO twice daily; olaparib plus bevacizumab 5 mg/kg IV once every 2 weeks; bevacizumab plus 5-FU 2400 mg/m2 IV over 46 to 48 hours every 2 weeks; or bevacizumab plus capecitabine 1000 mg/m2 PO twice daily for 14 days, then 7 days off, every 3 weeks. Treatment will continue until progressive disease or end of study.
The primary outcome measure is PFS, defined as time from randomization to first documented progressive disease or death due to any cause, whichever occurs first, per RECIST v1.1 as assessed by BICR for up to 6 years. Secondary outcome measures include OS, ORR, and DOR per RECIST v1.1 as assessed by BICR, the number of participants with ≥1 AEs, and the number of participants discontinuing study intervention due to an AE. The study plans to enroll 525 participants throughout the United States and worldwide. For more information, contact Merck Sharpe & Dohme Corp. at 1-888-577-8839 or
7 Eflornithine plus Sulindac to Prevent Recurrence of Second Primary CRCs in Patients with Previously Treated Stage 0-III Disease
The purpose of this double-blind, placebo-controlled, randomized phase 3 trial is to assess whether the combination of eflornithine and sulindac has efficacy in preventing recurrence of high-risk adenomas and secondary primary CRCs in patients with previously treated stage 0-III colon or rectal cancer. Patients aged ≥18 years with a history of stage 0-III colon or rectal cancer with previous primary resection 1 year before study induction; who have postoperative colonoscopy or computed tomography scans of the chest, abdomen, and pelvis showing no evidence of disease; who have completed adjuvant chemotherapy and radiotherapy at least 30 days before study induction; who are not receiving or planning to receive concomitant IV corticosteroids on a regular basis, or nonsteroidal anti-inflammatory drugs or anticoagulants on a regular, predictable, intermittent basis; and who have an ECOG performance status of 0 to 1 may be eligible if other criteria are met. Eligible patients will be randomized to receive either 2 eflornithine 250-mg tablets PO daily for 3 years plus 1 sulindac 150-mg tablet PO daily for 3 years; eflornithine plus sulindac placebo tablet; sulindac plus eflornithine placebo tablets; or sulindac and eflornithine placebo tablets.
The primary outcome measure is the event rate, defined as the rate of high-risk adenoma or secondary primary CRC, for up to 3 years after study registration. Secondary outcome measures include the total advanced colorectal event rate, defined as the number of participants with ≥1 high-risk adenomas, secondary primary CRC, CRC recurrence, or metastasis; high-grade dysplasia; the number of participants with development of any adenoma >0.3 cm; the time to first clinically apparent high-risk adenoma or secondary primary CRC; thrombotic cardiovascular and ototoxic events collected as Common Technology Criteria for Adverse Events’ AEs; pharmacokinetic analysis; and biomarker identification based on integrated comprehensive droplet digital detection technology. The study plans to enroll 1340 participants throughout the United States and worldwide. For more information, contact Patricia N. O’Kane, BS, at 1-210-614-8808 extension 1011 or