28 Participants Needed

Chemoimmunotherapy for Colon Cancer

(NICER Trial)

HG
Overseen ByHector Garcia-Chavez, MD
Stay on Your Current MedsYou can continue your current medications while participating
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

Trial Summary

What is the purpose of this trial?

This is a Phase II open-label trial of neoadjuvant immunochemotherapy with Atezolizumab and CAPOX followed by surgery and potentially adjuvant chemotherapy for patients with localized resectable pMMR adenocarcinoma of the colon with a target accrual of 28 patients. The investigators will explore if appropriately timed neoadjuvant CAPOX with anti-PD-L1 mAb (Atezolizumab) can be administered safely and feasibly, and that this combination will lead to improved clinical response associated with enhanced numbers of immune cells in surgically resected colon tumors. Patients will receive 4 cycles of atezolizumab in combination with 4 cycles of CAPOX (atezolizumab will be administered prior to chemotherapy) before standard of care surgical resection. Following surgery, patients still considered to be at high-risk of recurrence (per SOC guidelines) will receive further adjuvant chemotherapy (mFOLFOX6 or CAPOX), based on the discretion of the treating oncologist/investigator. Circulating tumor DNA (ctDNA) dynamic change status will be analyzed through collection of blood samples throughout different stages of the patient's neoadjuvant treatment regimen (baseline, pre-neoadjuvant therapy, mid-neoadjuvant, post-neoadjuvant therapy, and during postoperative period) as a marker of early read on efficacy. The end of the study for each patient enrolled will be at the 6 month postoperative visit. On Study Protocol: Patients will be followed up for an efficacy follow-up phase during the first 6 months after surgery (week 2 \& months 3, 6 visits). All assessments beyond the 6 month visit will be performed under standard of care surveillance office visits. Off Study Protocol: Thereafter they will enter a survival follow-up phase per standard of care protocols. Patients will be seen every 6 months starting at month 12 until month 36. All collection of research-specific assessments including whole blood, stool collection and quality of life questionnaires will be optional beyond the 6 month postop visit (months 12-36).

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.

What data supports the effectiveness of the drug combination Atezolizumab, Tecentriq, Capecitabine, and Oxaliplatin for colon cancer?

Research shows that the combination of capecitabine and oxaliplatin is effective in treating advanced colorectal cancer, with response rates over 50% in first-line therapy. Additionally, Atezolizumab has been approved for use in other cancers, indicating its potential effectiveness in combination therapies.12345

Is chemoimmunotherapy for colon cancer safe?

The safety of chemoimmunotherapy for colon cancer, involving drugs like capecitabine, oxaliplatin, and atezolizumab, has been studied in various trials. Capecitabine is generally well tolerated, with manageable side effects like hand-foot syndrome and diarrhea. Atezolizumab has an acceptable safety profile, with common side effects including fatigue and nausea, and some serious immune-related reactions like pneumonitis and hepatitis.678910

What makes the drug Atezolizumab, Capecitabine, Oxaliplatin unique for colon cancer treatment?

This treatment combines Atezolizumab, a drug that helps the immune system fight cancer by targeting a specific protein (PD-L1), with chemotherapy drugs Capecitabine and Oxaliplatin. Atezolizumab is unique because it is a type of immunotherapy that has shown promise in treating certain types of colorectal cancer, especially in patients with specific genetic features (dMMR), offering a novel approach compared to traditional chemotherapy alone.1112131415

Research Team

AI

Atif Iqbal

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

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.
Signed Informed Consent Form
I am over 18 years old.
See 6 more

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.
See 23 more

Timeline

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)

Treatment Details

Interventions

  • Atezolizumab
  • Capecitabine, Oxaliplatin
Trial OverviewThe 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.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Neoadjuvant Therapy ArmExperimental Treatment3 Interventions
Subjects will receive 4 cycles of neoadjuvant atezolizumab in combination with 4 cycles of CAPEOX 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

Find a Clinic Near You

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 profile image

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway profile image

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Findings from Research

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.
New oxaliplatin-based combinations in the treatment of colorectal cancer.Cassidy, J., Hochster, H.[2019]
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.
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]
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.
Atezolizumab: First Global Approval.Markham, A.[2019]

References

New oxaliplatin-based combinations in the treatment of colorectal cancer. [2019]
Randomized multicenter phase II trial of two different schedules of capecitabine plus oxaliplatin as first-line treatment in advanced colorectal cancer. [2022]
Atezolizumab: First Global Approval. [2019]
A phase II study of capecitabine, oxaliplatin, bevacizumab and cetuximab in the treatment of metastatic colorectal cancer. [2021]
Quality-of-life findings from a randomised phase-III study of XELOX vs FOLFOX-6 in metastatic colorectal cancer. [2021]
Capecitabine safety profile, innovative and generic adjuvant formulation of nonmetastatic colorectal cancer. [2020]
U.S. Food and Drug Administration Approval Summary: Atezolizumab for Metastatic Non-Small Cell Lung Cancer. [2022]
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. [2022]
Pharmacology and therapeutic efficacy of capecitabine: focus on breast and colorectal cancer. [2015]
10.United Statespubmed.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. [2022]
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. [2022]
Adjuvant chemotherapy for stages II, III and IV of colon cancer. [2021]
13.United Statespubmed.ncbi.nlm.nih.gov
Targeted agents for adjuvant therapy of colon cancer. [2018]
14.United Statespubmed.ncbi.nlm.nih.gov
Targeted agents for adjuvant therapy of colon cancer. [2006]
Atezolizumab for the treatment of colorectal cancer: the latest evidence and clinical potential. [2022]