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 Nivolumab Monotherapy versus Nivolumab plus Ipilimumab Combination versus Chemotherapy in dMMR/MSI-H Metastatic CRC
The purpose of this randomized, parallel, phase 3 clinical trial is to compare the clinical benefit of nivolumab (Opdivo) monotherapy versus nivolumab plus ipilimumab (Yervoy) versus chemotherapy for the treatment of patients with microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) metastatic colorectal cancer (CRC). Patients aged ≥18 years with recurrent or metastatic CRC not amenable to surgery, who have known tumor MSI-H or dMMR status and an Eastern Cooperative Oncology Group (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 combination, or investigator’s choice of chemotherapy, with the ability to receive the combination treatment if their disease progresses.
The primary outcome measures include progression-free survival (PFS) by Blinded Independent Central Review (BICR) in the nivolumab plus ipilimumab combination arm versus the nivolumab monotherapy arm, and PFS by BICR in the nivolumab plus ipilimumab combination arm versus the chemotherapy only arm. Secondary outcome measures include overall response rate (ORR) among all treatment arms, overall survival (OS) among all treatment arms, and PFS by BICR among all randomized participants. The study plans to enroll 748 participants throughout the United States and worldwide. For more information, contact the recruiting sites directly and include the NCT # and Site # in the first line of the e-mail. If there is no contact information, e-mail
2 High-Dose Vitamin D3 Added to Chemotherapy plus Bevacizumab in Previously Untreated Advanced or Metastatic CRC
The purpose of this randomized, double-blind, phase 3 clinical trial is to assess the efficacy of adding high-dose vitamin D3 to standard chemotherapy plus bevacizumab (Avastin) for the treatment of patients with previously untreated advanced or metastatic CRC. Patients aged ≥18 years with advanced or metastatic colorectal adenocarcinoma for which no metastasectomy is planned, who have not received previous systemic treatment for metastatic disease or who have received previous radiation therapy ≥4 weeks prior to registration or previous adjuvant therapy >12 months prior to recurrence, and who have an ECOG status of 0-1 may be eligible if other criteria are met. Eligible patients will be randomized to receive either high-dose vitamin D3 orally plus bevacizumab intravenously (IV) and chemotherapy for 14-day cycles for 5 years or standard-dose vitamin D3 orally plus bevacizumab IV and chemotherapy for 14-day cycles for 5 years in the absence of disease progression or unacceptable toxicity.
The primary outcome measure is PFS per RECIST version 1.1 in the comparison of both treatment arms with use of stratified analysis. Secondary outcome measures include ORR, OS, incidence of adverse events (AEs), comparison of physical activity and PFS in high-dose vitamin D3 versus standard-dose, incidence of vitamin D3 deficiency, and the prognostic effect of highest achieved serum 25-hydroxyvitamin D levels. This study plans to enroll 400 patients throughout the United States and worldwide. For more information, contact Kimmie Ng, MD, MPH, at 1-617-632-4150 or
3 Duloxetine Hydrochloride for the Prevention of Oxaliplatin-Induced Peripheral Neuropathy in Stage II-III CRC
The purpose of this randomized, double-blind, placebo-controlled, phase 2/3 clinical trial is to assess the efficacy of different doses of duloxetine hydrochloride (Cymbalta) to prevent peripheral neuropathy caused by oxaliplatin (Eloxatin) treatment in patients with stage II to III CRC. Patients aged ≥25 years with stage II-III CRC scheduled to receive oxaliplatin, who have not received previous neurotoxic chemotherapy or who do not have previously existing clinical or preclinical peripheral neuropathy from any cause, and who have an ECOG performance status of 0-2 may be eligible if other criteria are met. Eligible patients in phase 2 of the trial will be randomized to receive either duloxetine hydrochloride 30 mg orally once daily in week 1 and twice daily in week 2, plus placebo in weeks 2 to 16 followed by duloxetine hydrochloride 30 mg once daily in week 17; duloxetine hydrochloride 30 mg orally once daily in week 1, duloxetine hydrochloride 60 mg twice daily in weeks 2 to 16, and 30 mg once daily in week 17; or placebo for 17 weeks in the absence of unacceptable toxicity. Eligible patients in phase 3 will be randomized to receive the most promising dose of duloxetine hydrochloride or placebo.
The primary outcome measures include the prevention of sensory oxaliplatin-induced peripheral neuropathy response in phase 2 and phase 3 of the trial and chronic neuropathic pain response in phase 3. Secondary outcome measures include the incidence of AEs, including duloxetine side effects in phase 2 and 3 of the trial per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0; and serially measured total sensory neuropathy scores and patient-reported average pain scores as per the Quality of Life (QOL) Questionnaire – Chemotherapy-Induced Peripheral Neuropathy 20 in phase 3. The study plans to enroll 327 patients throughout the United States and Guam. For more information, contact Ellen M. Lavoie Smith, PhD, at 1-734-936-1267 or
4 Olaparib Alone or in Combination with Bevacizumab versus Bevacizumab plus 5-FU in Unresectable CRC
The purpose of this randomized, open-label, phase 3 clinical trial is to assess the efficacy and safety of olaparib (Lynparza) alone or in combination with bevacizumab versus bevacizumab plus 5-fluorouracil (5-FU) for the treatment of patients with unresectable or metastatic CRC whose disease has not progressed after first-line induction of folinic acid, fluorouracil, and oxaliplatin (FOLFOX) plus bevacizumab. Patients aged ≥18 years with metastatic or unresectable colorectal adenocarcinoma whose disease has not progressed after first-line induction treatment with FOLFOX plus bevacizumab, who have had unacceptable toxicity associated with oxaliplatin that required discontinuation, and who have an ECOG performance status of 0-1 within 10 days prior to randomization may be eligible if other criteria are met. Eligible patients will be randomized to receive either oral olaparib 300 mg twice daily plus bevacizumab 5 mg/kg IV once every 2 weeks until progressive disease or end of study; oral olaparib 300 mg twice daily until progressive disease or end of study; or bevacizumab 5 mg/kg IV every 2 weeks plus 5-FU 2400 mg/m2 IV over 46 to 48 hours every 2 weeks until progressive disease or end of study.
The primary outcome measure is PFS using RECIST version 1.1 as assessed by BICR from the time of randomization to the first documented progressive disease or death due to any cause, whichever occurs first. Secondary outcome measures include OS, ORR, duration of response, the number of participants with ≥1 AEs, and the number of participants discontinuing study intervention due to AEs. The study plans to enroll 525 patients throughout the United States and worldwide. For more information, contact Merck Sharp & Dohme Corp at 1-888-577-8839 or
5 Eflornithine plus Sulindac to Reduce 3-Year Rate of Adenomas and Secondary Primary CRC in Previously Treated CRC
The purpose of this randomized, double-blind, placebo-controlled, phase 3 clinical trial is to assess the efficacy of eflornithine (α-difluoromethylornithine) plus sulindac (Clinoril) in the prevention of high-risk dysplasias, adenomas, and secondary primary CRC recurrence in patients with previously treated stage 0-III CRC. Patients aged ≥18 years with a history of stage 0-III colon or rectal cancer with primary resection 1 year previously with postoperative colonoscopy and computed tomography scans of the chest, abdomen, and pelvis showing no evidence of disease, who have a Zubrod/ECOG performance status of 0-1, and who are not receiving or planning to receive concomitant IV corticosteroids on a regular basis may be eligible if other criteria are met. Eligible patients will be randomized to receive either 2 placebo tablets orally once daily for 3 years; 2 eflornithine 250-mg tablets orally daily plus 1 placebo tablet once daily for 3 years; 1 sulindac 150-mg tablet orally daily plus 2 placebo tablets orally daily for 3 years; or 2 eflornithine 250-mg tablets orally daily plus 1 sulindac 150-mg tablet once daily for 3 years.
The primary outcome measure is event rate, defined as the rate of high-risk adenoma or second primary CRC, for 3 years after registration. Secondary outcome measures include total advanced colorectal event rate, colon cancer recurrence, time to first clinically apparent high-risk adenoma or second primary CRC, toxicity as per CTCAE AEs, pharmacokinetic analysis, and biomarker identification based on the Integrated Comprehensive Droplet Digital Detection technology. This study plans to enroll 1340 participants throughout the United States. For more information, contact Patricia N. O’Kane, BS, at 1-210-614-8808 extension 1101 or
6 Chemotherapy plus Bevacizumab and/or Atezolizumab versus Atezolizumab Alone in Advanced or Metastatic CRC
The purpose of this randomized, parallel, phase 3 clinical trial is to assess the efficacy of modified combination chemotherapy (mFOLFOX6) plus bevacizumab with or without atezolizumab versus atezolizumab alone for the first-line treatment of patients with dMMR/MSI-H stage IV or metastatic CRC. Patients aged ≥18 years with dMMR/MSI-H metastatic adenocarcinoma of the colon or rectum who have not received previous chemotherapy or any other systemic therapy, who have an ECOG performance status of 0-2 and are not in immediate need for surgical intervention of the primary tumor or palliative diversion/bypass, may be eligible if other criteria are met. Eligible patients will be randomized to receive either bevacizumab IV on day 1 plus mFOLFOX6 on days 1 and 2 every 2 weeks until disease progression or unacceptable toxicity; atezolizumab IV on day 1 every 2 weeks for up to 48 cycles in the absence of disease progression or unacceptable toxicity; or atezolizumab IV on day 1 every 2 weeks for 48 cycles plus bevacizumab IV and mFOLFOX6 on day 1 every 2 weeks until disease progression or unacceptable toxicity.
The primary outcome measure is PFS from time of randomization until first confirmed progression or death from any cause, assessed up to 5 years. Secondary outcome measures include OS, ORR, incidence of AEs, disease control rate (complete response plus partial response plus stable disease), and duration of overall response and stable disease. Other outcome measures include severity of fatigue as measured by the Patient Reported Outcomes Measurement Information System Fatigue questionnaire, physical functioning measured by the European Organisation for Research and Treatment of Cancer QLQ-C30 scale, severity and frequency of QOL and patient-reported outcomes, change in quantification and the development of progression or relapse due to cell-free DNA mutations, and the efficacy in tumors with somatic mutations and tumors with MLH1 silencing. This study plans to enroll 231 patients throughout the United States. For more information, contact the sites directly. The NLM identifier is NCT02997228.
7 Myelopreservation and Antitumor Efficacy of Trilaciclib Prior to FOLFOXIRI plus Bevacizumab in Metastatic CRC
The purpose of this randomized, double-blind, placebo-controlled, global, multicenter, phase 3 clinical trial is to assess the effect of trilaciclib (Cosela) when added to folinic acid, fluorouracil, and irinotecan plus oxaliplatin (FOLFOXIRI) and bevacizumab regarding myelopreservation and antitumor efficacy in patients with metastatic CRC who have not received systemic therapy. Patients aged ≥18 years with proficient mismatch repair/microsatellite stable adenocarcinoma of the colon or rectum who have unresectable and measurable or evaluable disease per RECIST version 1.1, an ECOG performance status of 0-1, and adequate organ function may be eligible if other criteria are met. Eligible patients will be randomized 1:1 to receive either placebo or trilaciclib IV on days 1 and 2 prior to FOLFOXIRI plus bevacizumab in 14-day cycles for up to 12 cycles (Induction). Following completion of induction, patients will continue in maintenance, where they will receive trilaciclib or placebo per randomization allocation at study entry. Trilaciclib/placebo will be administered prior to infusional 5-FU/leucovorin/bevacizumab at the same dose and schedule used during induction. Patients may continue to receive treatment until disease progression, unacceptable toxicity, withdrawal of consent, discontinuation by investigator, or the end of the trial, whichever occurs first.
The primary outcome measure is myelopreservation as measured by duration of severe neutropenia in cycle 1 and occurrence of severe neutropenia during induction. Secondary outcome measures include QOL and effects on chemotherapy-induced fatigue and antitumor efficacy (PFS and OS) from the date of randomization until date of documented radiologic disease progression per RECIST version 1.1 or death due to any cause, whichever comes first. The study plans to enroll 296 participants throughout the United States and Spain. For more information, contact G1 Therapeutics Clinical Contact at 1-919-213-9835 or