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Educational tool only. Does not confirm eligibility or provide medical advice. Always consult your physician before pursuing any trial.

OncologyICD-10: C18

Find Recruiting Clinical Trials for Colorectal Cancer

Search MSI-H, KRAS/BRAF-mutant, metastatic, and early-stage colorectal cancer trials matched to your biomarkers and treatment history.

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About Colorectal Cancer

Colorectal cancer (CRC) is the second leading cause of cancer death in the United States, affecting the colon (colon cancer) or rectum (rectal cancer). The majority of cases arise from adenomatous polyps, and staging (I–IV) reflects depth of invasion and spread to lymph nodes or distant organs. Molecular profiling has fundamentally transformed CRC treatment and trial eligibility: key biomarkers include microsatellite instability status (MSI-H/dMMR vs. MSS/pMMR), RAS mutation status (KRAS and NRAS — wildtype vs. mutant), BRAF V600E mutation, HER2 amplification, and NTRK fusion. Standard treatment for metastatic CRC (mCRC) includes FOLFOX or FOLFIRI chemotherapy backbones combined with bevacizumab (all RAS) or cetuximab/panitumumab (RAS and BRAF wildtype, left-sided tumors). MSI-H/dMMR CRC (approximately 4–5% of metastatic cases) responds dramatically to checkpoint immunotherapy and is now treated with pembrolizumab as first-line therapy. Comprehensive genomic profiling (NGS panel) is now standard of care for metastatic CRC.

What Types of Colorectal Cancer Clinical Trials Exist?

CRC trial eligibility is almost entirely driven by molecular biomarker status and prior treatment history. MSI-H/dMMR CRC trials test novel immunotherapy combinations (LAG-3, TIGIT, TIM-3 inhibitors combined with PD-1/PD-L1 blockade) and neoadjuvant immunotherapy strategies. MSS/pMMR CRC trials — the majority of metastatic cases — test chemotherapy combinations, VEGF/VEGFR-targeted therapies, and novel mechanisms to overcome immunotherapy resistance. KRAS G12C-specific inhibitors (adagrasib, sotorasib in combinations) require confirmed KRAS G12C mutation. BRAF V600E trials test encorafenib combinations. RAS/BRAF-wildtype trials test EGFR inhibitor intensification and combinations. HER2-amplified CRC (2–3% of cases) has emerging targeted options. Right-sided tumors are less responsive to EGFR inhibitors regardless of RAS status. Prior lines of therapy (first-line, second-line, refractory) determine which trials are accessible.

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Data from ClinicalTrials.gov · Updated in real time · Educational use only

Frequently Asked Questions

What clinical trials are available for colorectal cancer?▾
Colorectal cancer has a robust and biomarker-stratified trial landscape. By molecular subtype: MSI-H/dMMR CRC (approximately 15% of all CRC, 4–5% of metastatic) trials test checkpoint immunotherapy combinations, neoadjuvant total neoadjuvant therapy (TNT) strategies (especially for rectal cancer), and maintenance immunotherapy approaches. MSS/pMMR metastatic CRC trials — the largest group — test novel chemotherapy doublets, VEGF pathway agents, TGF-beta inhibitors, and strategies to sensitize tumors to immunotherapy. KRAS G12C-mutant trials test adagrasib and sotorasib combinations. BRAF V600E trials (approximately 8–10% of mCRC) test encorafenib-based triplet regimens. HER2-amplified trials test trastuzumab deruxtecan and pertuzumab combinations. Early-stage CRC trials focus on adjuvant chemotherapy optimization and circulating tumor DNA (ctDNA) to guide treatment de-escalation. Comprehensive genomic profiling is essential before trial searching.
What does MSI-H mean and how does it affect colorectal cancer trial eligibility?▾
MSI-H stands for microsatellite instability-high, and dMMR stands for deficient mismatch repair — these two terms describe the same molecular feature and are used interchangeably. Mismatch repair (MMR) proteins correct DNA replication errors; when these proteins are deficient (due to germline mutations in Lynch syndrome or somatic silencing), errors accumulate at short repetitive DNA sequences called microsatellites, resulting in MSI-H status. MSI-H/dMMR CRC tumors have a very high mutational burden, making them exceptionally responsive to immune checkpoint inhibitors (anti-PD-1/PD-L1 antibodies like pembrolizumab and nivolumab). MSI-H status is now tested in all newly diagnosed CRC patients via immunohistochemistry (IHC) for MMR proteins or PCR/NGS for microsatellite markers. For metastatic MSI-H CRC, pembrolizumab is approved as first-line therapy. In clinical trials, MSI-H status opens eligibility for novel immunotherapy combinations and neoadjuvant strategies — and MSI-H patients are generally excluded from standard chemotherapy-based trials that would be offered to MSS patients.
Does KRAS mutation status affect colorectal cancer trial eligibility?▾
Yes — KRAS mutation status is one of the most critical eligibility determinants in colorectal cancer. KRAS mutations occur in approximately 40–45% of CRC cases. Any KRAS or NRAS mutation (collectively called RAS mutations) disqualifies patients from anti-EGFR antibody trials (cetuximab, panitumumab and their combinations), as these agents are ineffective in RAS-mutant tumors. However, a specific mutation — KRAS G12C — present in approximately 3–4% of CRC cases, opens eligibility for KRAS G12C-targeted inhibitor trials testing adagrasib (Krazati) and sotorasib (Lumakras) combinations, which have shown promising activity. BRAF V600E mutations (approximately 8–10% of CRC, largely mutually exclusive with RAS mutations) also require specific targeted therapies (encorafenib + cetuximab). The practical implication: patients with metastatic CRC should have comprehensive genomic profiling (NGS panel testing tumor tissue or liquid biopsy) before trial searching, as mutation status determines which trials are relevant.
How does colorectal cancer stage affect which clinical trials I can join?▾
Stage fundamentally determines the trial landscape. Stage I–II (localized, no lymph node involvement): trials focus on surgical technique optimization, adjuvant chemotherapy de-escalation guided by ctDNA (circulating tumor DNA), and surveillance strategies. Many patients with stage I–II CRC do not require systemic therapy and may not be eligible for drug trials. Stage III (lymph node positive, no distant metastases): adjuvant FOLFOX trials test duration optimization, CAPOX variations, and ctDNA-guided approaches to avoid over-treatment. Stage IV (distant metastases): the most active trial category; eligibility is primarily driven by biomarker status (MSI-H, KRAS, BRAF, HER2), tumor sidedness (right vs. left colon), and prior lines of therapy. Liver-limited metastatic CRC may access conversion therapy trials aimed at making resectable disease initially unresectable. Rectal cancer specifically has active total neoadjuvant therapy (TNT) and organ preservation trials that may be applicable before surgery.

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Data source: All clinical trial information is sourced from ClinicalTrials.gov, the official U.S. registry maintained by the National Library of Medicine. Tidera Health is an independent educational platform and is not affiliated with ClinicalTrials.gov or the National Library of Medicine. Always verify trial details directly with the research coordinator or your physician.