FOLFOX Chemotherapy for Rectal Cancer

Not currently recruiting at 1 trial location

Overseen By Chris LeFeber

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Rochester

Disqualifiers: Metastatic disease, Unresectable cancer, Cardiovascular, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 10

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a chemotherapy treatment called FOLFOX to determine if it can help people with locally advanced rectal cancer avoid radiation and surgery. The goal is to discover if this approach can completely treat the cancer. The treatment involves receiving medications every two weeks for a total of 10 cycles. The trial seeks participants who have been newly diagnosed with rectal cancer, particularly those whose cancer hasn't spread and who haven't received previous cancer treatments. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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 anticoagulant therapy, you must be on a stable dose to participate.

Is there any evidence suggesting that FOLFOX is likely to be safe for humans?

Research has shown that FOLFOX, a type of chemotherapy, is generally safe for many people with rectal cancer. In one study, patients who received FOLFOX before surgery experienced less diarrhea and had better bowel function compared to some other treatments, indicating that patients usually tolerate FOLFOX well.

Moreover, a safety review of over 3,300 patients from various areas found no major safety issues with FOLFOX. Some patients required dose adjustments, a common practice in chemotherapy to manage side effects.

Overall, FOLFOX is known to be manageable for patients, with side effects that are usually milder than those from some other treatments. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about mFOLFOX for rectal cancer because it offers a modified approach to the existing FOLFOX regimen, which is already a staple in treating colorectal cancers. This regimen combines three drugs: oxaliplatin, leucovorin, and 5-fluorouracil (5-FU), administered in a specific sequence. The modification in mFOLFOX involves a specific dosing schedule and delivery method, where patients receive the treatment every other week over a series of 10 cycles, which could enhance the effectiveness and tolerability of the therapy. This approach may provide a more manageable treatment timeline and potentially improved outcomes compared to traditional regimens.

What evidence suggests that FOLFOX might be an effective treatment for rectal cancer?

Research has shown that FOLFOX chemotherapy effectively treats rectal cancer that hasn't spread far. In one study, 80.8% of patients who received FOLFOX remained cancer-free five years later, which is very encouraging. Patients on FOLFOX also experienced better bowel function and less diarrhea compared to some other treatments. Another study found that using FOLFOX before the main treatment, such as surgery, led to better results than surgery alone. Overall, the evidence supports FOLFOX as a strong option for fighting rectal cancer. Participants in this trial will receive a modified version of FOLFOX, known as mFOLFOX, administered every other week for 10 cycles. ^{1 2 6 7 8}

Who Is on the Research Team?

Richard Dunne, MD

Principal Investigator

University of Rochester

Are You a Good Fit for This Trial?

Adults diagnosed with locally advanced rectal cancer who haven't had previous treatments or radiation, and have no history of other cancers in the last 3 years. They must meet specific blood work criteria, not be pregnant or planning to conceive, and agree to use contraception. Those with certain heart conditions, active infections, or peripheral neuropathy are excluded.

Inclusion Criteria

Platelet count>100,000/mm3

Baseline lab work must meet the following parameters:

I do not have any infections needing IV antibiotics.

Exclusion Criteria

I do not have heart, liver, or kidney diseases that would prevent me from receiving chemotherapy.

My cancer is at a specific stage and size.

I do not have severe numbness or pain in my hands or feet.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemotherapy

Participants receive 10 cycles of FOLFOX chemotherapy, administered every other week, with interval analysis after six cycles

20 weeks

10 visits (in-person)

Surveillance

Participants undergo close surveillance with watchful waiting for local recurrence without immediate surgery

1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• FOLFOX

Trial Overview The trial is testing FOLFOX chemotherapy without radiation and surgery for complete response in treating locally advanced rectal cancer. It aims to see if patients can achieve remission with this approach alone.

How Is the Trial Designed?

Group I: mFOLFOX (5-Fluorouracil Leucovorin Oxaliplatin) Experimental Treatment 1 Intervention

Patients treated on protocol will be treated with modified FOLFOX. Patients will receive 10 cycles of FOLFOX, administered every other week. FOLFOX will be given on day 1 of each cycle. Patients will receive oxaliplatin 85 mg/m² IV over 120 minutes, leucovorin 400 mg/m² IV over 120 minutes, 5-FU 400 mg/m² IVP followed by 5-FU 2400 mg/m² infuse over 46 hours.

FOLFOX is already approved in United States, European Union, Japan, China for the following indications:

Approved in United States as FOLFOX for:

• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction adenocarcinoma

Approved in European Union as FOLFOX for:

• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction adenocarcinoma

Approved in Japan as FOLFOX for:

• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction adenocarcinoma

Approved in China as FOLFOX for:

• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction adenocarcinoma

Who Is Running the Clinical Trial?

University of Rochester

Lead Sponsor

Trials

883

Recruited

555,000+

Published Research Related to This Trial

In a study of 41 patients with lower rectal cancer, four courses of mFOLFOX6 chemotherapy before surgery resulted in a 3-year recurrence-free survival rate of 72.8% and a local recurrence rate of 8.5%, indicating a promising long-term oncological benefit.

Patients with clinical Stage III cancer who received adjuvant chemotherapy after the initial mFOLFOX6 treatment had a significantly higher 3-year recurrence-free survival rate (76.6%) compared to those who did not receive adjuvant therapy (40.0%), suggesting the importance of additional treatment for this group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The survival impact of preoperative FOLFOX for resectable locally advanced rectal cancer: the R-NAC-01 study. Ichikawa, N., Homma, S., Funakoshi, T., et al.[2022]

The combination of fluorouracil and folinic acid (LV-5FU2 protocol) is the preferred first-line treatment for metastatic colorectal cancer, showing better efficacy and tolerability compared to other protocols like the Mayo Clinic protocol.

Adding oxaliplatin (FOLFOX protocol) or irinotecan (FOLFIRI protocol) to the fluorouracil + folinic acid regimen improves tumor response rates and survival times, although these combinations also increase the risk of severe side effects such as neuropathy and diarrhea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy of metastatic colorectal cancer: fluorouracil plus folinic acid and irinotecan or oxaliplatin. [2013]

In a study of 1033 colorectal cancer patients treated with 5-fluorouracil (5FU) based adjuvant therapy, certain adverse events like neutropenia, nausea/vomiting, and mucositis were linked to better disease-free survival (DFS) and overall survival (OS).

Patients who experienced any grade of neutropenia had a 19% lower risk of disease progression, while those with nausea/vomiting had a 38% lower risk of death, suggesting that these adverse effects may serve as positive indicators of treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of adverse events and survival in colorectal cancer patients treated with adjuvant 5-fluorouracil and leucovorin: Is efficacy an impact of toxicity? Soveri, LM., Hermunen, K., de Gramont, A., et al.[2014]

In patients with inoperable or metastatic colorectal cancer, initial treatment with single-agent fluorouracil (or capecitabine) is recommended over combination therapies when the disease is unlikely to become operable, as it does not shorten overall survival compared to combination regimens.

The addition of monoclonal antibodies like cetuximab and panitumumab in first-line treatment has not shown a significant improvement in overall survival, suggesting their use should be reconsidered, particularly in patients with KRAS mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy of metastatic colorectal cancer. [2013]

In patients with unresectable RAS wild-type metastatic colorectal cancer, first-line bevacizumab-based chemotherapy significantly reduces the risk of dermatological and renal adverse events, but increases the risk of cardiovascular issues like hypertension and arrhythmia.

Conversely, cetuximab-based chemotherapy is associated with a higher incidence of dermatological and renal adverse events, particularly rashes and electrolyte disorders, highlighting the need for careful selection of targeted therapies based on safety profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability on Serious Adverse Events of First-Line Bevacizumab and Cetuximab for RAS Wild-Type Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis. Han, YN., Choi, YJ., Rhie, SJ.[2022]

In a study of 110 Asian patients with metastatic colorectal cancer, those treated with the mFOLFOX6 regimen including a 5-FU bolus had a significantly lower absolute neutrophil count (ANC) compared to those who did not receive the bolus, indicating a potential risk for neutropenia.

The findings suggest that omitting the 5-FU bolus from the mFOLFOX6 regimen may be necessary for patients at high risk of hematological adverse events, particularly neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Impact of Omitting 5-FU Bolus From mFOLFOX6 Chemotherapy Regimen on Hematological Adverse Events Among Patients With Metastatic Colorectal Cancer. Areepium, N., Sapapsap, B.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5896363/

Comparisons of Efficacy, Safety, and Cost of Chemotherapy ... The objective of this study was to compare outcome measures, adverse effects, and cost of FOLFOX4 and FOLFIRINOX treatments in rectal cancer patients.

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2303269

Preoperative Treatment of Locally Advanced Rectal Cancer Five-year disease-free survival was 80.8% (95% CI, 77.9 to 83.7) in the FOLFOX group and 78.6% (95% CI, 75.4 to 81.8) in the chemoradiotherapy ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10351948/

Patient-Reported Outcomes During and After Treatment for ... In conclusion, during neoadjuvant treatment, patients treated with FOLFOX experienced less diarrhea and better bowel function than those treated with 5FUCRT but ...

4. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-024-12634-7

Combination of neoadjuvant and adjuvant chemotherapy with ... In this study, neoadjuvant chemotherapy (group A) significantly improves outcomes compared to surgery alone (group B) in treating locally ...

5. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.19.00016

Oxaliplatin-Based Adjuvant Chemotherapy for Rectal ... Six-year overall survival rate was 78.1% in the FOLFOX arm versus76.4% in the FL arm (hazard ratio, 0.73; 95% CI, 0.45 to 1.19; P = .21). In the ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.4_suppl.133

Total neoadjuvant therapy with FOLFOX plus bevacizumab ... All patients completed the prescribed TNT cycles, and six (12.8%) of them had dose reduction. The CR was achieved in 18 (38.3%) patients, ...

7. oncnursingnews.com oncnursingnews.com/view/pro-analysis-of-prospect-trial-reveals-distinct-toxicity-profiles-with-folfox-vs-chemoradiation-in-rectal-cancer

PRO Analysis of PROSPECT Trial Reveals Distinct Toxicity ... Overall, patients who received neoadjuvant FOLFOX (n = 493) achieved lower rates of diarrhea and better overall bowel function (P < .05).

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1533002811001253

Safety Analysis of FOLFOX4 Treatment in Colorectal ... The comparison of safety profiles of the FOLFOX4 treatment between 1515 Asian patients and 1844 Western patients demonstrated that there was no evidence that ...