Chemotherapy + Atezolizumab for Colon Cancer

Not currently recruiting at 1222 trial locations

Overseen By Shannon B. Keating

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must not be taking: Corticosteroids, Immunosuppressive medications

Disqualifiers: Autoimmune disease, Hepatitis B/C, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 20

Duration: 24-50 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding atezolizumab, an immunotherapy drug, to standard chemotherapy can more effectively treat stage III colon cancer. It compares this combination approach to standard chemotherapy alone to determine which better stops cancer growth. Patients with stage III colon cancer who have a specific genetic feature (deficient DNA mismatch repair) may be suitable candidates. Participants will receive either the combination treatment or just chemotherapy and will undergo regular scans to monitor progress. As a Phase 3 trial, this study represents the final step before FDA approval, providing patients an opportunity to contribute to potentially groundbreaking treatment advancements.

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, you cannot be on systemic daily treatment with corticosteroids or other immunosuppressive medications within 7 days of registration.

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

Research has shown that adding atezolizumab to standard chemotherapy is generally safe. One study found that the side effects of this combination resemble those already known for FOLFOX (a type of chemotherapy) and PD-L1 blockade (a type of immunotherapy). Patients might experience similar side effects, including some immune-related issues, but these are expected and typical for this kind of therapy.

In this setting, atezolizumab has been well-tolerated when used with chemotherapy. Specifically, the combination reduced the risk of cancer recurrence or death by 50% compared to chemotherapy alone. This important finding suggests the treatment is effective while keeping side effects manageable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for colon cancer?

Researchers are excited about the treatment of colon cancer with the combination of chemotherapy and Atezolizumab because it introduces a novel approach by including immunotherapy. Unlike standard treatments that typically involve chemotherapy drugs like Leucovorin Calcium, Fluorouracil, and Oxaliplatin, this regimen adds Atezolizumab, an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells more effectively. This combination has the potential to enhance the body's natural defenses against cancer, potentially leading to better outcomes. Additionally, this treatment could offer a new option for patients whose cancer may not respond well to traditional chemotherapy alone.

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

Research has shown that adding atezolizumab to standard chemotherapy can improve outcomes for patients with a specific type of colon cancer characterized by DNA mismatch repair deficiency. This trial will compare two treatment arms: one where participants receive a combination of chemotherapy and atezolizumab, and another where participants receive chemotherapy alone. Studies have found that this combination treatment reduces the risk of cancer returning or causing death by 50% compared to chemotherapy alone. Specifically, one study showed that 86.4% of patients who received atezolizumab with chemotherapy had no signs of cancer after three years, compared to 76.6% of those who only had chemotherapy. Atezolizumab helps the immune system attack cancer cells, potentially stopping them from growing and spreading. This promising evidence supports the potential effectiveness of combining atezolizumab with chemotherapy for treating this type of colon cancer. ^{2 6 7 8 9}

Who Is on the Research Team?

Frank A Sinicrope

Principal Investigator

Alliance for Clinical Trials in Oncology

Are You a Good Fit for This Trial?

This trial is for patients with stage III colon cancer and deficient DNA mismatch repair. Eligible participants must not have autoimmune diseases, active hepatitis B or C, severe allergies to certain antibodies or components in atezolizumab, nor require daily steroids or immunosuppressants. They should have proper liver and kidney function, no history of severe allergic reactions to specific proteins, and no prior treatments except possibly one cycle of mFOLFOX6.

Inclusion Criteria

My kidney function, based on creatinine levels, is normal for my age and gender.

My platelet count is above the required level for my treatment stage.

I am 12 years old or older.

Exclusion Criteria

Your oxygen levels without extra oxygen are below 85%.

Your oxygen levels are below 88% even with extra oxygen.

I do not have active lung disease causing low oxygen levels.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive combination chemotherapy with or without atezolizumab. Chemotherapy includes oxaliplatin, leucovorin calcium, and fluorouracil. Atezolizumab is administered in Arm I.

24-50 weeks

Every 14 days for up to 25 cycles

Follow-up

Participants are monitored for disease recurrence and survival. Imaging and blood sample collection are conducted.

5 years

Every 6 months for 2 years, then annually for 3 years

Long-term follow-up

Participants are followed up for survival every 6 months for up to 8 years.

8 years

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Leucovorin Calcium, Fluorouracil, Oxaliplatin

Trial Overview

The study compares the effectiveness of combination chemotherapy alone versus with atezolizumab in treating stage III colon cancer. Chemotherapy includes drugs like oxaliplatin, leucovorin calcium, and fluorouracil that kill or stop tumor cells from growing. Atezolizumab is an immunotherapy that may boost the immune system's attack on cancer.

How Is the Trial Designed?

Group I: Arm I (combination chemotherapy, atezolizumab) Experimental Treatment 8 Interventions

Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV as a bolus on day 1, then continuously over 46 hours on days 1-3 of each cycle. Treatment repeats every 14 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive atezolizumab IV over 30-60 minutes on day 1 of each cycle, beginning in cycle 1 or 2. Treatment repeats every 14 days for up to 25 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT or MRI every 6 months for the first 2 years, then for years 3-5 or until evidence of relapse, whichever comes first. Patients may also undergo blood sample collection throughout the trial.

Group II: Arm II (combination chemotherapy) Active Control 7 Interventions

Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV as a bolus on day 1, then continuously over 46 hours on days 1-3 of each cycle. Treatment repeats every 14 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT or MRI every 6 months for the first 2 years, then for years 3-5 or until evidence of relapse, whichever comes first. Patients may also undergo blood sample collection throughout the trial.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 570 patients with stage III colorectal cancer, three different administration types of 5-fluorouracil (5-FU) in FOLFOX treatment showed similar disease-free survival (DFS) and overall survival (OS) rates, indicating comparable efficacy.

While all treatment regimens were manageable in terms of toxicity, the modified FOLFOX-6 group experienced more grade 1-2 adverse events like thrombocytopenia and neuropathy, suggesting that while efficacy is similar, side effects may vary among the different regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The comparison of FOLFOX regimens with different doses of 5-FU for the adjuvant treatment of colorectal cancer: a multicenter study. Akdeniz, N., Kaplan, MA., Uncu, D., et al.[2021]

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 II study involving 46 patients with advanced colorectal cancer resistant to previous treatments, the FOLFOX2 regimen (oxaliplatin, leucovorin, and 5-FU) achieved a high overall response rate of 46%, including one complete response and 20 partial responses.

The treatment was associated with manageable toxicities, primarily neutropenia (39%) and peripheral neuropathy (9%), indicating that while the regimen is effective, careful monitoring for these side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxaliplatin with high-dose leucovorin and 5-fluorouracil 48-hour continuous infusion in pretreated metastatic colorectal cancer. de Gramont, A., Vignoud, J., Tournigand, C., et al.[2019]

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]

In a phase II trial involving 82 patients with advanced colorectal cancer, the combination of cetuximab and FOLFOX6 showed an overall response rate of 44.8%, indicating its efficacy as a first-line treatment.

Patients who developed skin toxicity while on the treatment had significantly longer median survival times (21.7 months) compared to those who did not experience this side effect, suggesting a potential correlation between skin reactions and treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of FOLFOX6 and cetuximab in the first-line treatment of patients with metastatic colorectal cancer. Boccia, RV., Cosgriff, TM., Headley, DL., et al.[2016]

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]

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