Chemotherapy +/− Bevacizumab for Stage II Colon Cancer

Not currently recruiting at 1049 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Disqualifiers: Inflammatory bowel disease, Hypertension, Heart failure, 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: 27

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding bevacizumab, a monoclonal antibody that may block tumor growth, to a standard chemotherapy regimen is more effective than chemotherapy alone in treating stage II colon cancer after surgery. Participants will receive one of two chemotherapy combinations: one with bevacizumab and one without, or they might be observed without further treatment. Individuals who have undergone surgery for stage II colon cancer and have no history of inflammatory bowel disease or other tumors might be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

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

Research has shown that a combination of chemotherapy drugs—5-fluorouracil, leucovorin, and oxaliplatin—along with bevacizumab is generally well-tolerated by patients with colon cancer. One study found this combination effective and well-tolerated, particularly for patients whose colorectal cancer has spread.

Another study found that adding bevacizumab to chemotherapy worked well for patients with metastatic colorectal cancer, indicating safety in similar treatment situations. Some unwanted side effects were reported, but they were manageable.

Overall, safety data from these studies suggest that this treatment combination can be used safely in patients with colon cancer. Participants should still consult their doctor about possible side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they explore the potential addition of bevacizumab to standard chemotherapy for stage II colon cancer. The standard care typically involves chemotherapy drugs like fluorouracil, leucovorin, and oxaliplatin, which target cancer cells directly. The unique aspect of this study is the use of bevacizumab, a drug that works differently by inhibiting blood vessel growth that tumors need to grow and spread. This approach could potentially improve outcomes by cutting off the tumor's blood supply, making it harder for the cancer to survive and advance.

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

Studies have shown that adding oxaliplatin to the chemotherapy treatment of fluorouracil (5-FU) and leucovorin benefits colon cancer patients. This combination, known as FOLFOX, outperforms using just 5-FU and leucovorin. In this trial, some participants will receive the FOLFOX regimen alone, while others will receive FOLFOX combined with bevacizumab, a monoclonal antibody. Research indicates that bevacizumab can enhance treatment by inhibiting cancer growth and spread. Using bevacizumab with FOLFOX has proven very effective and shows promise in controlling the disease. These findings suggest that using all four drugs together could be more effective than chemotherapy alone in treating colon cancer. ^{3 6 7 8 9}

Who Is on the Research Team?

Al B Benson

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

This trial is for patients who've had surgery for stage II colon cancer. They should have stable blood pressure, no severe neuropathy, and no history of inflammatory bowel disease or significant bleeding unrelated to their tumor. Participants must not have started any other treatments for this cancer, be in good physical condition (ECOG 0-2), and agree to use contraception if applicable. Those with certain heart conditions or a history of serious blood clots can't join.

Inclusion Criteria

Patients must have >= 8 lymph nodes evaluated and reported

I have a tumor sample available for specific genetic testing.

Low-risk patients will be registered to Arm C for observation

Exclusion Criteria

I have had a condition where my lymphocytes multiply unusually.

I haven't had any cancer except for skin cancer in the last 5 years.

I have not had a heart attack or unstable angina in the last year.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive oxaliplatin, leucovorin calcium, and fluorouracil with or without bevacizumab every 2 weeks for 12 courses

24 weeks

12 visits (in-person)

Bevacizumab Extension

Patients in Arm B receive bevacizumab alone for 12 additional courses

24 weeks

12 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

15 years

Every 3 months for 2 years, every 6 months for 3 years, then annually for 10 years

What Are the Treatments Tested in This Trial?

Interventions

• Bevacizumab
• Fluorouracil
• Laboratory Biomarker Analysis
• Leucovorin Calcium
• Oxaliplatin

Trial Overview The study compares two treatment methods after surgery: one group receives chemotherapy drugs oxaliplatin, leucovorin calcium, fluorouracil alone; the other gets these drugs plus bevacizumab, an antibody that may block tumor growth. The goal is to find out which combination is more effective against colon cancer.

How Is the Trial Designed?

Group I: Arm B (5-FU, leucovorin, oxaliplatin, bevacizumab) Experimental Treatment 4 Interventions

Patients receive oxaliplatin, leucovorin, and fluorouracil as in Arm A and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 2 weeks for 12 courses in the absence of disease progression or unacceptable toxicity. Patients then receive bevacizumab alone for 12 additional courses in the absence of disease progression or unacceptable toxicity.

Group II: Arm A (5-FU, leucovorin, oxaliplatin) Active Control 3 Interventions

Patients receive oxaliplatin IV over 2 hours and leucovorin IV over 2 hours on day 1. Patients also receive fluorouracil IV continuously over 46 hours beginning on day 1. Treatment repeats every 2 weeks for 12 courses in the absence of disease progression or unacceptable toxicity.

Group III: Arm C (observation) Active Control 1 Intervention

Patients undergo observation.

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

Approved in United States as 5-Fluorouracil for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer
• Skin cancer

Approved in European Union as 5-Fluorouracil for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer

Approved in Canada as 5-Fluorouracil for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer

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 retrospective analysis of patients with metastatic colorectal cancer, bevacizumab significantly improved progression-free survival (PFS) and overall survival (OS) in patients aged 65 and older, showing similar benefits to younger patients.

While older patients experienced an increase in thromboembolic events when treated with bevacizumab, no other significant age-related increases in severe adverse events were noted, indicating a manageable safety profile for this age group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of bevacizumab in older patients with metastatic colorectal cancer: pooled analysis of four randomized studies. Cassidy, J., Saltz, LB., Giantonio, BJ., et al.[2022]

Postoperative adjuvant chemotherapy with fluorouracil (5-FU) and leucovorin significantly improves disease-free and overall survival in patients with node-positive (stage III) colorectal cancer, based on clinical trials involving over 5,000 cases.

Current clinical trials are exploring the effectiveness of combining 5-FU/leucovorin with other agents like irinotecan and oxaliplatin, which have shown superior results compared to 5-FU/leucovorin alone in advanced colorectal cancer, aiming to refine the standard of care for resected cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant therapy of colon cancer. Macdonald, JS., Astrow, AB.[2019]

In a study of 107 patients with metastatic colorectal cancer, the combination of irinotecan plus bevacizumab showed similar efficacy to FOLFIRI plus bevacizumab, with median progression-free survival of 6.4 months versus 5.8 months, and overall survival of 16.6 months versus 16.5 months, respectively.

Omitting fluorouracil from the FOLFIRI regimen resulted in fewer adverse events, such as nausea and neutropenia, suggesting that irinotecan plus bevacizumab may be a safer second-line treatment option for patients who are refractory to fluoropyrimidines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of omitting fluorouracil from FOLFIRI plus bevacizumab as second-line chemotherapy for patients with metastatic colorectal cancer. Matsubara, Y., Masuishi, T., Ogata, T., et al.[2023]

Oral fluoropyrimidines, such as capecitabine and UFT/LV, offer a more convenient and less toxic alternative to traditional intravenous 5-fluorouracil (5-FU) for treating advanced colorectal cancer (CRC).

Oxaliplatin, with a different mechanism of action than 5-FU, significantly improves response rates and time to disease progression when used in combination with 5-FU and leucovorin in first-line treatment, and is effective even in patients whose cancer has progressed after 5-FU treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel chemotherapy agents for colorectal cancer: oral fluoropyrimidines, oxaliplatin, and raltitrexed. Royce, ME., Hoff, PM., Padzur, R.[2019]

Bevacizumab, a monoclonal antibody that targets VEGF, significantly improves response rates, time to tumor progression, and overall survival in patients with advanced colorectal cancer when added to fluorouracil-based chemotherapy regimens, based on two clinical trials.

While bevacizumab shows efficacy in treating advanced colorectal cancer, it is associated with serious safety concerns, including thromboembolic events, hypertension, hemorrhage, and gastrointestinal perforation, highlighting the need for careful monitoring and further studies comparing its effectiveness with other chemotherapy options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab for advanced colorectal cancer. Hadj Tahar, A.[2013]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3259429/

Effectiveness of Adjuvant Chemotherapy with 5-FU ... This study aimed to identify the effects of 5-FU/LV adjuvant chemotherapy without oxaliplatin in patients with pathologically proven stage II colon cancer.

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa032709

Oxaliplatin, Fluorouracil, and Leucovorin as Adjuvant ... Adding oxaliplatin to a regimen of fluorouracil and leucovorin improves the adjuvant treatment of colon cancer. Colorectal cancer is the second leading cause of ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3394600/

Role of oxaliplatin combined with 5-fluorouracil and folinic ... Evidence on first-line treatment found infusional 5-fu/fa/oxaliplatin (folfox) to be superior to bolus 5-fu/fa/irinotecan (ifl) for rates of median survival ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1533002814001285

A Review of the Evolution of Systemic Chemotherapy in ... As first-line therapy, FOLFIRI achieved an RR of 56% and PFS of 8.5 months, and for FOLFOX the RR was 54% (P = NS) and the PFS was 8.0 months (P = NS). The ...

5. ar.iiarjournals.org ar.iiarjournals.org/content/33/3/1053

Comparative Effectiveness of 5-Fluorouracil with and ... Conclusion: Our findings suggested no survival benefit with the addition of oxaliplatin to 5-FU modalities in treating CRC in practice. This raises questions as ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC1894803/

Front-line Bevacizumab in combination with Oxaliplatin ... The combination of FOLFOX4/bevacizumab appears to be highly effective, well tolerated and merits further evaluation in patients with mCRC.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT01640405

NCT01640405 | Study of 5-Fluorouracil/Leucovorin ... The purpose of the study is to evaluate FOLFOX + bevacizumab versus FOLFOXIRI + bevacizumab as first line treatment of patients with metastatic colorectal ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9588906/

A phase I/II study of arfolitixorin and 5-fluorouracil in ... The phase III AGENT study (NCT03750786) is exploring the efficacy of arfolitixorin versus leucovorin in combination with 5-FU, oxaliplatin, and ...

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0959804912009811

Efficacy and safety of bevacizumab-based combination ... The combination of bevacizumab and bolus 5-fluorouracil, leucovorin and irinotecan is highly effective in patients with metastatic colorectal cancer (mCRC).