Chemoimmunotherapy for Colon Cancer

(NICER Trial)

Overseen By Hector Garcia-Chavez, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Baylor College of Medicine

Must not be taking: Antibiotics, Immunosuppressants, Immunostimulants, others

Disqualifiers: Metastatic disease, Autoimmune disease, Cardiovascular disease, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 14

28 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for individuals with a specific type of colon cancer. Researchers aim to determine if combining immunotherapy, which aids the immune system in fighting cancer, with chemotherapy before surgery can improve outcomes. The treatment uses Atezolizumab (Tecentriq, an immunotherapy drug) and CAPOX (a chemotherapy regimen including Capecitabine and Oxaliplatin) to enhance the body's response to surgery. Individuals with non-metastatic colon cancer and certain risk factors, such as high tumor markers or specific imaging results, may be suitable for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in colon cancer treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on certain treatments like systemic immunosuppressive medications or investigational therapies, you may need to stop them before starting the trial. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study showed that combining atezolizumab with standard chemotherapy improved outcomes for colon cancer patients. This combination reduced the risk of cancer recurrence or death by 50% compared to chemotherapy alone. Another study found that side effects matched those expected from similar treatments, with no unexpected side effects. However, some patients experienced immune system-related issues, which are common with this therapy type.

For the CAPOX treatment, which includes capecitabine and oxaliplatin, safety has been thoroughly researched. Reports indicated that about 31% of patients experienced severe side effects, and around 18% required hospital care due to these effects. While these numbers might seem high, they are typical for this kind of cancer treatment.

Overall, both atezolizumab and CAPOX are considered safe based on their known side effects. It's important to discuss with a doctor how these treatments might affect an individual personally. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about this chemoimmunotherapy combination because it harnesses the power of atezolizumab, an immunotherapy drug that helps the immune system attack cancer cells, alongside capecitabine and oxaliplatin, which are traditional chemotherapies. Unlike standard treatments for colon cancer that often involve chemotherapy alone, this approach uses a checkpoint inhibitor (atezolizumab) to potentially enhance the body's natural defenses against cancer. This combination aims to reduce the size of tumors before surgery and may lower the risk of cancer returning, offering a more comprehensive attack on the disease. By integrating immunotherapy with chemotherapy, this treatment strategy hopes to provide a more effective option for patients at high risk of recurrence.

What evidence suggests that this trial's treatments could be effective for colon cancer?

In this trial, participants will receive a combination of atezolizumab, a type of immunotherapy, with chemotherapy as part of the neoadjuvant therapy arm. Research has shown that combining atezolizumab with chemotherapy can significantly reduce the chance of colon cancer returning. Studies have found that adding atezolizumab to standard chemotherapy cuts the risk of cancer recurrence by 50% compared to chemotherapy alone. One study revealed that 86.4% of patients who received both atezolizumab and chemotherapy showed no signs of cancer after three years. The combination of Capecitabine and Oxaliplatin, known as CAPOX, has also proven effective for patients at high risk of cancer recurrence. Overall, this combination treatment shows promise in reducing the likelihood of colon cancer returning. ^{2 6 7 8 9}

Who Is on the Research Team?

Atif Iqbal

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

This trial is for adults over 18 with resectable, non-metastatic colon cancer that's not spread and has specific molecular features (pMMR). They must be able to follow the study plan, have certain high-risk factors like large tumors or signs of spreading to lymph nodes, and be in good physical condition. People can't join if they've had severe lung disease, recent heart issues, major surgery within a month, active infections including TB or hepatitis B/C/HIV, received live vaccines recently, are pregnant/breastfeeding or planning pregnancy soon.

Inclusion Criteria

My tumor is located more than 12 cm from the anal opening, based on tests or surgery.

My tumor is not MSI-high as determined by specific tests.

Signed Informed Consent Form

Exclusion Criteria

I haven't had major heart problems in the last 3 months.

I have not had a severe infection in the last 4 weeks.

I have not had major surgery in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Neoadjuvant Therapy

Participants receive 4 cycles of neoadjuvant immunochemotherapy with Atezolizumab and CAPOX over 12 weeks before surgery

12 weeks

4 visits (in-person)

Surgery

Surgical removal of the tumor is performed per standard-of-care practices

1 day

1 visit (in-person)

Efficacy Follow-up

Participants are monitored for efficacy and safety during the first 6 months post-surgery

6 months

3 visits (in-person)

Adjuvant Chemotherapy

High-risk patients receive adjuvant chemotherapy based on the discretion of the treating oncologist

Variable

Long-term Follow-up

Participants are followed for survival and recurrence every 6 months from month 12 to month 36

24 months

5 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Capecitabine, Oxaliplatin

Trial Overview The trial tests neoadjuvant CAPEOX chemotherapy combined with Atezolizumab (an immunotherapy drug) before surgery followed by more chemo if needed. It aims to see if this treatment shrinks tumors better and improves immune response. Patients get four cycles of both drugs every three weeks pre-surgery; high-risk patients may receive additional chemo post-surgery based on guidelines.

How Is the Trial Designed?

Group I: Neoadjuvant Therapy Arm Experimental Treatment 3 Interventions

Subjects will receive 4 cycles of neoadjuvant atezolizumab in combination with 4 cycles of CAPOX before standard of care surgical resection. After surgery, patients who are still considered high risk for recurrence (per the treating medical oncologist) will be offered adjuvant therapy.

Atezolizumab is already approved in United States, European Union for the following indications:

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Published Research Related to This Trial

Oxaliplatin-based regimens, such as FOLFOX or FLOX, are currently the standard adjuvant chemotherapy for high-risk stage II and stage III colon cancer after complete resection, improving overall survival rates.

Alternatives like capecitabine or continuous infusion of 5FU/LV are recommended for patients who cannot tolerate oxaliplatin, while the effectiveness of monoclonal antibodies like cetuximab and bevacizumab in combination with standard therapies is still being explored in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant chemotherapy for stages II, III and IV of colon cancer. Grávalos, C., García-Escobar, I., García-Alfonso, P., et al.[2021]

In patients with colorectal cancer (CRC), adjuvant therapy has shown a modest survival benefit, with the introduction of oxaliplatin reducing the risk of relapse by 23% compared to 5-fluorouracil alone, highlighting its efficacy in improving outcomes for stage II and III disease.

Targeted agents like bevacizumab and cetuximab are being investigated for their potential to enhance survival rates in the adjuvant therapy setting, with bevacizumab already demonstrating improved efficacy in advanced-stage CRC when combined with other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted agents for adjuvant therapy of colon cancer. Saif, MW.[2018]

The phase II study involving 23 patients tested the combination of capecitabine, oxaliplatin, and cetuximab with or without bevacizumab for metastatic colorectal cancer, revealing that both treatment arms were well tolerated but had different outcomes.

The results indicated that combining VEGF and EGFR inhibitors (arm A) led to a lower overall response rate (36.4%) and shorter median survival (18.0 months) compared to the treatment without bevacizumab (arm B), which had a response rate of 72.7% and a median survival of 42.5 months, suggesting that dual inhibition may be detrimental.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of capecitabine, oxaliplatin, and cetuximab with or without bevacizumab as frontline therapy for metastatic colorectal cancer. A Fox Chase extramural research study. Dotan, E., Meropol, NJ., Burtness, B., et al.[2022]

In a study of 89 patients with advanced colorectal cancer, a higher dose of capecitabine combined with oxaliplatin (arm B) resulted in a better response rate (54.5% vs. 42.2%) and significantly longer progression-free survival (10.5 months vs. 6.0 months) compared to a lower dose regimen (arm A).

Despite the increased dose intensity of capecitabine in arm B, there was no significant difference in hematologic toxicity or nonhematologic adverse events between the two treatment arms, indicating that the higher dose was well-tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized multicenter phase II trial of two different schedules of capecitabine plus oxaliplatin as first-line treatment in advanced colorectal cancer. Scheithauer, W., Kornek, GV., Raderer, M., et al.[2022]

In a study involving 8734 patients with stage III colon cancer, there was no significant difference in disease-free survival, relapse-free survival, or overall survival between patients treated with capecitabine and those treated with leucovorin and fluorouracil, regardless of whether oxaliplatin was included.

Combination therapy with oxaliplatin, whether paired with capecitabine or leucovorin and fluorouracil, consistently improved treatment outcomes without negatively impacting post-relapse survival, supporting its use as the standard of care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of adjuvant capecitabine or fluorouracil, with or without oxaliplatin, on survival outcomes in stage III colon cancer and the effect of oxaliplatin on post-relapse survival: a pooled analysis of individual patient data from four randomised controlled trials. Schmoll, HJ., Twelves, C., Sun, W., et al.[2022]

Atezolizumab, a monoclonal antibody targeting PD-L1, shows promising efficacy in treating metastatic colorectal cancer (mCRC), particularly in patients with deficient mismatch repair (dMMR), indicating a potential new treatment avenue for this subgroup.

Ongoing clinical trials suggest that atezolizumab may be even more effective when combined with chemotherapy or targeted therapies, such as the MEK inhibitor cobimetinib, paving the way for its inclusion in future treatment protocols for mCRC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for the treatment of colorectal cancer: the latest evidence and clinical potential. Tapia Rico, G., Price, TJ.[2022]

Atezolizumab significantly improves overall survival in patients with metastatic non-small cell lung cancer (mNSCLC), with median survival times of 13.8 months in the atezolizumab group compared to 9.6 months in the docetaxel group in the OAK trial.

The treatment has an acceptable safety profile, with common side effects including fatigue and decreased appetite, and serious immune-related adverse events occurring in a small percentage of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

U.S. Food and Drug Administration Approval Summary: Atezolizumab for Metastatic Non-Small Cell Lung Cancer. Weinstock, C., Khozin, S., Suzman, D., et al.[2022]

Capecitabine is an effective oral prodrug for treating metastatic breast cancer and stage III or IV colorectal cancer, showing preferential conversion to its active form, 5-fluorouracil, in tumor tissues, which enhances its efficacy and specificity.

The drug is generally well tolerated, with low rates of severe side effects like myelosuppression and alopecia, making it a favorable option for combination therapies with other anticancer agents, particularly taxanes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacology and therapeutic efficacy of capecitabine: focus on breast and colorectal cancer. Aprile, G., Mazzer, M., Moroso, S., et al.[2015]

Adjuvant therapy for colorectal cancer primarily involves combinations of 5-fluorouracil/leucovorin (5-FU/LV) with oxaliplatin or capecitabine, which are standard treatments aimed at improving patient outcomes after surgery.

The addition of targeted therapies like bevacizumab and cetuximab to these regimens is currently being tested in multiple clinical trials, indicating a potential for enhanced efficacy in treating advanced colon cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted agents for adjuvant therapy of colon cancer. de Gramont, A., Tournigand, C., André, T., et al.[2006]

In a study of 50 patients with nonmetastatic colorectal cancer, adverse reactions were more frequent with the XELOX regimen (capecitabine combined with oxaliplatin), particularly neurotoxicity, thrombocytopenia, and neutropenia, compared to capecitabine monotherapy.

The type of capecitabine formulation (innovative vs. generic) did not significantly affect the safety profile; instead, the chemotherapy scheme used was the main factor influencing the occurrence of adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine safety profile, innovative and generic adjuvant formulation of nonmetastatic colorectal cancer. Sánchez-Gundín, J., Torres-Suárez, AI., Fernández-Carballido, AM., et al.[2020]

In a phase III trial involving 1,886 patients with stage III colon cancer, the combination of capecitabine and oxaliplatin (XELOX) demonstrated a manageable safety profile, with treatment-related adverse events occurring at similar rates to the standard treatment of fluorouracil/leucovorin (FU/LV).

Patients receiving XELOX experienced less diarrhea and alopecia but had higher rates of neurosensory toxicity and hand-foot syndrome compared to those on FU/LV, indicating that while XELOX is generally well-tolerated, it may have specific side effects that need monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III trial of capecitabine plus oxaliplatin as adjuvant therapy for stage III colon cancer: a planned safety analysis in 1,864 patients. Schmoll, HJ., Cartwright, T., Tabernero, J., et al.[2022]

In a phase-III trial involving 306 patients with metastatic colorectal cancer, XELOX (capecitabine plus oxaliplatin) was found to be non-inferior to FOLFOX-6 (5-fluorouracil/leucovorin plus oxaliplatin) in terms of efficacy, indicating it is a viable first-line treatment option.

Patients receiving XELOX reported greater convenience and satisfaction, spending fewer days on hospital visits and losing less time from work or daily activities compared to those on FOLFOX-6, while maintaining similar quality of life scores.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality-of-life findings from a randomised phase-III study of XELOX vs FOLFOX-6 in metastatic colorectal cancer. Conroy, T., Hebbar, M., Bennouna, J., et al.[2021]

The combination of oxaliplatin with oral fluoropyrimidines like capecitabine (XELOX) has shown over 50% response rates in first-line treatment for advanced colorectal cancer, indicating its efficacy.

Ongoing studies are exploring various combinations of oxaliplatin with biological therapies, such as cetuximab and bevacizumab, which target different cancer pathways, potentially leading to improved treatment outcomes for patients with advanced disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New oxaliplatin-based combinations in the treatment of colorectal cancer. Cassidy, J., Hochster, H.[2019]

Atezolizumab is a monoclonal antibody that targets PD-L1, which is being developed for treating various blood cancers and solid tumors, showing promise in cancer immunotherapy.

It has already been approved in the US as a second-line treatment for urothelial carcinoma and is pending approval for non-small cell lung cancer, highlighting its potential efficacy in these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. Markham, A.[2019]

In a study of 30 patients with advanced colorectal cancer, the combination of capecitabine, oxaliplatin, bevacizumab, and cetuximab resulted in an overall response rate of 43%, with a median overall survival of 18.8 months.

Despite the promising response rate, the addition of cetuximab did not enhance the efficacy of the three-drug regimen and was associated with significant toxicities, including skin rash and sensory neuropathy, leading to frequent dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of capecitabine, oxaliplatin, bevacizumab and cetuximab in the treatment of metastatic colorectal cancer. Wong, NS., Fernando, NH., Nixon, AB., et al.[2021]

Citations

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ATOMIC). | Journal of Clinical Oncology Conclusion: The addition of atezolizumab to mFOLFOX6 significantly improved DFS and should be considered the new adjuvant standard of care for ...

2. targetedonc.com targetedonc.com/view/atezolizumab-chemo-reduces-risk-of-recurrence-or-death-by-50-in-dmmr-colon-cancer

Atezolizumab/Chemo Reduces Risk of Recurrence or ... The combination of atezolizumab (Tecentriq) and standard chemotherapy reduced the risk of recurrence or death by 50% vs chemotherapy alone in patients with ...

3. asco.org asco.org/practice-patients/patient-resources/breaking-cancer-news-patients/asco-annual-meeting/atomic

Atezolizumab plus chemotherapy leads to 50% lower risk ... For patients with stage III dMMR colon cancer, treatment with atezolizumab and mFOLFOX6 chemotherapy leads to a 50% lower risk of cancer recurrence and ...

4. ecancer.org ecancer.org/en/news/26552-asco-2025-atezolizumab-chemo-combo-leads-to-improved-survival-in-deficient-mismatch-repair-colon-cancer

ASCO 2025: Atezolizumab chemo combo leads to ... In the atezolizumab plus FOLFOX group, 86.4% of patients did not have any evidence of cancer after 3 years. In the FOLOFX alone group, 76.6% of ...

5. uclahealth.org uclahealth.org/news/release/combination-immunotherapy-and-targeted-therapy-improves

Combination of immunotherapy and targeted therapy ... Outcomes for metastatic colorectal cancer remain poor, with only about 15% of patients surviving five years. Patients whose cancer no longer ...

6. dana-farber.org dana-farber.org/newsroom/news-releases/2025/adding-immune-checkpoint-inhibitor-to-standard-chemotherapy-regimen-improves-outcomes-in-stage-3-colon-cancer-study-finds

Adding Immune Checkpoint Inhibitor to Standard ... Results from the ATOMIC trial reveal that the three-year disease-free survival was 86.4% (95% confidence interval, 81.8 to 89.9) in the ...

7. dailynews.ascopubs.org dailynews.ascopubs.org/do/atomic-atezolizumab-folfox-significantly-improves-dfs-reduces-recurrence-risk-stage-iii

ATOMIC: Atezolizumab + FOLFOX Significantly Improves ... The addition of atezolizumab to standard chemotherapy significantly improves DFS in patients with stage III dMMR colon cancer and yields a 50% reduction in the ...

8. onclive.com onclive.com/view/dr-sinicrope-on-the-efficacy-and-safety-of-mfolfox6-plus-atezolizumab-in-stage-iii-dmmr-crc

Dr Sinicrope on the Efficacy and Safety of mFOLFOX6 Plus ... "The combination of mFOLFOX6 and atezolizumab resulted in a 50% reduction in recurrence or death in patients [with dMMR CRC] compared with ...

9. allianceforclinicaltrialsinoncology.org allianceforclinicaltrialsinoncology.org/main/public/standard.xhtml?path=/Public/News-ATOMIC-Jun2025

Alliance Presents Results from Phase III ATOMIC Trial ... The safety profile of the combination regimen was consistent with known toxicities of FOLFOX and PD-L1 blockade. Immune-related adverse events ( ...