Clinical Trials for Colorectal Cancer: How to Find Studies

Colorectal cancer is the third most commonly diagnosed cancer in the United States and remains a major area of clinical research, particularly for metastatic disease and emerging targeted-therapy approaches. The American Cancer Society estimates roughly 158,850 new colon and rectal cancer diagnoses in the U.S. in 2026, and the field continues to evolve — immunotherapy in microsatellite instability-high (MSI-H) tumors, KRAS G12C inhibitors, HER2-targeted therapies, and combinations aimed at previously untargetable mutations. For patients with colorectal cancer, clinical trials for colorectal cancer can provide access to advanced therapies for treatment-resistant disease and to emerging approaches in earlier stages. This guide covers what a trial actually is, how to find colorectal cancer trials, the active research areas in 2026, eligibility considerations, your rights as a participant, and why screening still matters.

What a clinical trial is — and the four phases

A clinical trial is a carefully designed research study that tests whether a new treatment, combination, or strategy is safe and works better than what is already available. Trials follow a general sequence of phases, and knowing the phase helps set realistic expectations:

• Phase 1: First testing in a small group, focused mainly on safety, dosing, and side effects. Some phase 1 cancer trials are for people who have exhausted standard options.
• Phase 2: A larger group receives the treatment to see how well it works for a specific cancer and to gather more safety data.
• Phase 3: The treatment is compared with the current standard of care, often in a randomized design across many centers, to confirm benefit.
• Phase 4: After approval, ongoing studies track long-term safety and effectiveness in wider use.

Deciding to join a trial is a personal choice, and there is no “right” answer. Participation is voluntary and free of stigma — people join trials at every stage of illness, from newly diagnosed to heavily pretreated, and choosing not to enroll is equally valid.

Categories of colorectal cancer trials

Active colorectal cancer trials in 2026 include:

KRAS G12C inhibitors: Sotorasib and adagrasib have established activity in colorectal cancer (less effective than in lung cancer but meaningful), with newer KRAS inhibitors and combination approaches in development.

Immunotherapy combinations: Beyond MSI-H tumors where checkpoint inhibitors are effective, trials test immunotherapy combinations in microsatellite stable (MSS) tumors using novel mechanisms — TIM-3, LAG-3, TIGIT, and combinations with other agents.

HER2-targeted therapy: About 3-5% of colorectal cancers have HER2 amplification or overexpression, with trials testing trastuzumab deruxtecan (Enhertu), tucatinib combinations, and other HER2 approaches.

BRAF V600E-mutant disease: The combination of encorafenib plus cetuximab established activity; trials test next-line options and combinations with immunotherapy.

Adjuvant therapy in early-stage disease: Studies testing whether intensified or de-escalated chemotherapy regimens improve outcomes in stage II-III colon cancer.

Circulating tumor DNA (ctDNA)-guided treatment: Trials using ctDNA detection to guide adjuvant-therapy decisions, potentially identifying which patients benefit from chemotherapy after surgery.

Rectal cancer: Total neoadjuvant therapy approaches and watch-and-wait protocols for patients with a complete clinical response.

Where to find colorectal cancer trials

Resources for colorectal cancer trial searches:

• ClinicalTrials.gov — the U.S. government registry of studies worldwide
• National Cancer Institute (NCI) clinical trials search
• Colorectal Cancer Alliance — patient resources and trial matching
• Fight Colorectal Cancer — advocacy and trial information
• NCI-Designated Cancer Centers
• Major academic medical centers with GI oncology programs (MSKCC, MD Anderson, Dana-Farber, Mayo, and others)

Comprehensive molecular testing of the tumor is essential for matching with appropriate targeted-therapy and immunotherapy trials.

How to search ClinicalTrials.gov step by step

ClinicalTrials.gov can look overwhelming, but a few filters make it manageable:

• Condition: enter “colorectal cancer” (or “colon cancer” / “rectal cancer”) in the condition field.
• Other terms: add a molecular marker or drug class if you know it (for example “KRAS G12C” or “HER2”).
• Recruitment status: filter to “Recruiting” and “Not yet recruiting” to find open studies.
• Location: add your city, state, or a travel radius to find nearby sites.
• Study phase and eligibility: check the phase and the detailed inclusion/exclusion criteria before contacting a site.

Each listing includes a contact for the study team. The NCI search is often friendlier for patients and lets a nurse navigator help you interpret results. Whatever you find, bring the study numbers to your oncologist — a listing is a starting point, not a substitute for a conversation with your care team.

Molecular testing for trial matching

Key molecular features that affect colorectal cancer trial eligibility:

• Microsatellite status: MSI-H or MMR-deficient tumors (~5% of metastatic colorectal cancer) are eligible for immunotherapy approaches; MSS tumors require different strategies
• RAS mutation status: KRAS, NRAS mutations affect EGFR-targeted therapy eligibility and qualify for KRAS G12C inhibitors specifically
• BRAF V600E: About 8-10% of metastatic colorectal cancer; eligible for targeted combinations
• HER2 status: 3-5% of metastatic disease; eligible for HER2-targeted approaches
• NTRK fusion: Rare (
• Tumor mutational burden (TMB): High TMB may predict immunotherapy response

Most patients with metastatic colorectal cancer should have comprehensive genomic profiling at diagnosis or progression. Major academic centers offer this testing as standard care.

Typical eligibility for colorectal cancer trials

Common inclusion criteria:

• Confirmed colorectal cancer diagnosis (colon or rectal)
• Stage matching the trial’s target population
• Specific molecular profile (for targeted-therapy trials)
• Performance status (ECOG 0-2 typically)
• Adequate organ function
• Measurable disease (for response-based trials in metastatic disease)
• Specific prior therapy history

Common exclusion criteria:

• Other active cancers
• Recent major bowel obstruction or perforation
• Active uncontrolled inflammatory bowel disease
• Pregnancy
• Significant cardiac disease
• Active autoimmune disease (for immunotherapy trials)

Your rights: informed consent and the right to withdraw

Before you join any trial, the study team must take you through informed consent: a plain-language explanation of the study’s purpose, what procedures and treatments are involved, the potential benefits, the known and possible risks, and the alternatives — including standard treatment outside the trial. You should have time to read the consent form, ask questions, and take it home to discuss with family before signing. Signing is not a contract that locks you in.

Participation is voluntary, and you have the right to withdraw at any time, for any reason, without penalty and without losing the care you are otherwise entitled to. (Data already collected before you withdraw generally remains part of the study record, but no new study procedures continue.) Trials are also overseen by an Institutional Review Board (IRB) that reviews the study to protect participants’ safety and rights.

A trial is research, not guaranteed treatment

It is important to keep expectations realistic. A clinical trial is designed to answer a question, and the experimental treatment may turn out to work better, the same, or worse than standard care — that is precisely what the study is testing. Some trials are randomized, meaning a computer assigns you to one group or another, and some include a control arm. Joining a trial does not guarantee you will receive the new treatment or that it will help you. What trials do offer is careful monitoring and access to approaches that are not yet widely available. Discuss the specific design of any study — its phase, randomization, and what happens if the treatment does not work — with your oncologist.

Don’t stop your current treatment to enroll

If you are already on a cancer treatment, never stop it or delay it to chase a trial without your oncologist’s guidance. Timing, “washout” periods between treatments, and prior-therapy requirements are part of a trial’s eligibility rules, and your care team can coordinate any transition safely. Making changes on your own can jeopardize both your current treatment and your eligibility for the study.

Trials in metastatic disease

Patients with metastatic colorectal cancer often have multiple trial options:

First-line trials: Test new combinations or sequencing strategies vs. current standards such as FOLFOX/FOLFIRI plus targeted therapy.

Second- and third-line trials: Test novel mechanisms after standard chemotherapy — KRAS G12C inhibitors, BRAF-targeted combinations, immunotherapy combinations in MSS disease.

Refractory disease trials: Test salvage approaches in patients who have exhausted standard options, often phase 1 or early phase 2 with novel mechanisms.

For metastatic colorectal cancer, comprehensive molecular profiling and access to NCI-Designated Cancer Centers can expand trial options substantially.

Adjuvant therapy trials

Trials in stage II-III colon cancer test whether modifications to standard adjuvant chemotherapy improve cure rates:

• Duration of adjuvant chemotherapy (3 vs. 6 months — the IDEA collaboration established 3 months as adequate for many lower-risk stage III patients)
• ctDNA-guided adjuvant therapy (DYNAMIC, COBRA, and other trials testing whether ctDNA detection guides treatment intensity)
• Adjuvant immunotherapy in MSI-H disease
• De-escalation in low-risk disease

Patients with stage II-III colorectal cancer should discuss adjuvant trial options with their oncologist after surgery.

Rectal cancer trials

Rectal cancer treatment has evolved significantly. Active research areas:

Total neoadjuvant therapy (TNT): Giving all chemotherapy and radiation before surgery rather than splitting it between pre- and post-surgery. PRODIGE-23, RAPIDO, and others established TNT approaches.

Watch-and-wait protocols: Patients with a complete clinical response after neoadjuvant therapy may avoid surgery, with intensive monitoring for regrowth. The OPRA trial helped establish watch-and-wait as a viable option for selected patients.

Immunotherapy in MSI-H rectal cancer: An influential study of neoadjuvant dostarlimab in mismatch-repair-deficient rectal cancer reported striking complete clinical response rates in its initial cohorts — among the most notable results in recent oncology, though it involves a small, selected group and longer-term, larger studies are ongoing.

What participation involves

Colorectal cancer trials typically involve:

• Comprehensive baseline workup including CT/PET imaging, labs, ECG, and tumor biopsy with molecular profiling
• Treatment with the experimental therapy in cycles, often every 2-4 weeks
• Imaging assessments every 6-12 weeks
• Lab monitoring for toxicities
• Sometimes ctDNA monitoring
• Long-term follow-up

For metastatic disease, treatment typically continues until progression. For adjuvant trials, treatment is time-limited and followed by years of follow-up.

Screening still matters: start at age 45

Trials are for people who already have colorectal cancer, but the single most powerful tool against the disease is catching it early — or preventing it — through screening. The U.S. Preventive Services Task Force (USPSTF) recommends that average-risk adults begin colorectal cancer screening at age 45 and continue through age 75, with screening from 76 to 85 decided individually. Options include colonoscopy and stool-based tests such as FIT (fecal immunochemical test) and stool DNA tests; talk with your clinician about which is right for you. This matters more than ever because colorectal cancer is rising in adults under 50. If you have a family history, symptoms such as rectal bleeding or a change in bowel habits, or other risk factors, you may need to start earlier — ask your doctor.

Frequently Asked Questions

Do I need molecular testing for colorectal cancer trials?

It is strongly recommended for metastatic disease. Microsatellite status, RAS, BRAF, HER2, and tumor mutational burden all affect trial eligibility. Most academic centers perform comprehensive testing as standard care.

Are MSI-H colorectal cancer trials different from MSS trials?

Yes. MSI-H tumors respond to immunotherapy and have specific trials testing immunotherapy combinations and approaches. MSS tumors require different strategies; immunotherapy alone is generally less effective in MSS disease.

What’s the watch-and-wait approach for rectal cancer?

Patients with a complete clinical response after neoadjuvant chemoradiation may be monitored intensively rather than proceeding straight to surgery. This can avoid surgical morbidity but requires close surveillance for regrowth, and it is appropriate only for carefully selected patients guided by an experienced team.

Can I participate in adjuvant trials after colon surgery?

Yes. Adjuvant trials enroll patients after surgery to test modifications to standard chemotherapy. Discuss options with your oncologist before starting standard adjuvant therapy, since timing matters.

Are colorectal cancer screening trials available?

Yes. Trials test new screening modalities (blood-based tests, novel imaging) and approaches to improve screening uptake. The USPSTF screening recommendations are informed in part by ongoing research.

Does joining a trial cost money?

The study sponsor usually covers the cost of the experimental treatment and study-specific tests, while routine care costs are typically billed to insurance. Ask the study team and your insurer exactly what is and isn’t covered, including travel, before you enroll.

The bottom line on colorectal cancer trials

Colorectal cancer trials cover the full spectrum from prevention and screening through adjuvant therapy and metastatic disease. Molecular profiling is essential for matching with mutation-specific and immunotherapy trials. For patients with metastatic disease — particularly those with treatment-resistant cancer or rare molecular subtypes — trials can offer access to advanced therapies, while remaining research rather than guaranteed treatment. Adjuvant trials test ways to improve cure rates after surgery, and rectal cancer trials are exploring less-invasive approaches. Enrollment is always voluntary, protected by informed consent and the right to withdraw. Discuss trial options — and never stop current treatment on your own to pursue one — with your oncologist as part of comprehensive treatment planning, and don’t overlook the power of on-time screening.

Sources

• ClinicalTrials.gov — U.S. registry of clinical studies
• National Cancer Institute — Clinical trials search and patient information
• USPSTF — Colorectal Cancer: Screening recommendation (start at age 45)
• American Cancer Society — Colorectal cancer key statistics, 2026