Chemotherapy + Atezolizumab for Colon Cancer

Recruiting at 1183 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

700 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing whether adding atezolizumab to standard chemotherapy works better than chemotherapy alone for patients with stage III colon cancer who have a specific genetic defect. The chemotherapy drugs aim to kill cancer cells, while atezolizumab helps the immune system attack the cancer. Researchers hope this combination will improve survival rates and quality of life for these patients.

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.

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

Research shows that adding oxaliplatin to fluorouracil and leucovorin improves survival in colon cancer patients. This combination, known as FOLFOX, is a standard treatment for certain stages of colon cancer, suggesting its effectiveness in this context. ^{1 2 3 4 5}

Is the combination of chemotherapy drugs and Atezolizumab safe for colon cancer treatment?

The combination of chemotherapy drugs like oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX) has been studied for colon cancer, showing some side effects such as nerve damage, low white blood cell counts, and mouth sores. These side effects are common but manageable, and the treatment is generally considered safe for use in humans. ^{6 7 8 9 10}

How is the drug combination of chemotherapy and Atezolizumab unique for colon cancer treatment?

This treatment combines standard chemotherapy drugs (Leucovorin Calcium, Fluorouracil, Oxaliplatin) with Atezolizumab, an immunotherapy drug that helps the immune system attack cancer cells. This combination is unique because it adds an immune-boosting component to the traditional chemotherapy regimen, potentially enhancing the overall effectiveness against colon cancer. ^{10 11 12 13 14}

Research Team

Frank A Sinicrope

Principal Investigator

Alliance for Clinical Trials in Oncology

Eligibility Criteria

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

I am 12 years old or older.

You need to have a certain number of a type of white blood cell called neutrophils in your blood.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

A phase II trial of FOLFOX6 and cetuximab in the first-line treatment of patients with metastatic colorectal cancer. [2016]

2. England pubmed.ncbi.nlm.nih.gov

New oxaliplatin-based combinations in the treatment of colorectal cancer. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Clinical Outcome From Oxaliplatin Treatment in Stage II/III Colon Cancer According to Intrinsic Subtypes: Secondary Analysis of NSABP C-07/NRG Oncology Randomized Clinical Trial. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

A phase II study of S-1, oxaliplatin, oral leucovorin, and bevacizumab combination therapy (SOLA) in patients with unresectable metastatic colorectal cancer. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Effect of oxaliplatin, fluorouracil, and leucovorin with or without cetuximab on survival among patients with resected stage III colon cancer: a randomized trial. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Safety analysis of FOLFOX4 treatment in colorectal cancer patients: a comparison between two Asian studies and four Western studies. [2021]

7. Germany 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. [2021]

8. United States 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. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Oxaliplatin with high-dose leucovorin and 5-fluorouracil 48-hour continuous infusion in pretreated metastatic colorectal cancer. [2019]

10. England 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. [2022]

11. Italy pubmed.ncbi.nlm.nih.gov

Recommendations and expert opinion on the adjuvant treatment of colon cancer in Spain. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. [2022]

13. New Zealand pubmed.ncbi.nlm.nih.gov

Oxaliplatin: in operable colorectal cancer. [2018]

14. United States pubmed.ncbi.nlm.nih.gov

Adjuvant therapy of colon cancer: current status and future directions. [2018]