FOLFOX Regimen for Rectal Cancer

Overseen By Namrata Vijayvergia, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Fox Chase Cancer Center

Must be taking: FOLFOX

Must not be taking: Antiretrovirals, Investigational agents

Disqualifiers: Advanced adenocarcinoma, Prior chemotherapy, 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: 5

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment plan for early-stage rectal cancer using a chemotherapy regimen called FOLFOX, followed by surgery and additional therapy. The goal is to determine if this combination can effectively treat cancer without requiring more invasive procedures later. It suits those diagnosed with early-stage rectal cancer who have not received prior treatment. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in cancer care.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are on certain medications like antiretroviral therapy for HIV, you may not be eligible to participate. It's best to discuss your current medications with the trial team to get a clear answer.

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

Studies have shown that the FOLFOX treatment is generally safe for people with rectal cancer. Research indicates that most people tolerate this treatment well. One study found that a version of FOLFOX used before surgery, called mFOLFOX6, was a safe option for treating rectal cancer, with a low risk of serious side effects. Another study found that patients often had successful surgeries after using FOLFOX, suggesting the treatment did not cause issues that would interfere with surgery. While all treatments can have side effects, evidence so far suggests FOLFOX is a safe choice for rectal cancer patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the FOLFOX regimen for rectal cancer because it offers a promising alternative to traditional radiation therapy and surgical options. FOLFOX combines chemotherapy drugs like 5-fluorouracil, leucovorin, and oxaliplatin, which work together to target cancer cells more effectively. Unlike the standard treatments that often involve radiation, FOLFOX is focused on using chemotherapy to shrink tumors before surgery, which can potentially minimize side effects and improve surgical outcomes. This approach could revolutionize the way rectal cancer is treated by prioritizing less invasive methods with the potential for better patient experiences.

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

Research has shown that the FOLFOX treatment is effective for rectal cancer, especially when administered before surgery. One study found that about 81% of patients who received FOLFOX remained cancer-free five years after treatment, indicating a low recurrence rate during that period. This trial will evaluate FOLFOX as neoadjuvant chemotherapy, exploring its potential effectiveness even without prior radiation. This approach could be promising for those with early-stage rectal cancer, offering a less invasive treatment with favorable outcomes. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with early stage, low rectal adenocarcinoma who haven't had treatment for it before. They must be in good health with normal organ and marrow function and not pregnant or breastfeeding. People with certain high-risk tumors, previous malignancies needing systemic therapy within the last 3 years, HIV on antiretroviral therapy, or other serious illnesses are excluded.

Inclusion Criteria

My cancer is in an early stage and hasn't spread to my lymph nodes.

I have not received any treatment for rectal cancer.

I am fully active or can carry out light work.

Exclusion Criteria

I cannot receive FOLFOX chemotherapy and pelvic radiation due to health reasons.

My T1 tumor is larger than 4 cm, has lymphovascular invasion, or is not well differentiated.

My rectal cancer has spread to my lymph nodes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Neoadjuvant Chemotherapy

Systemic therapy with FOLFOX is administered

12 weeks

Regular visits for chemotherapy administration

Restaging and Local Excision

Restaging of the primary tumor and local excision for responders

6-12 weeks after chemotherapy

1-2 visits for restaging and surgery

Post-operative Chemoradiotherapy

5-FU based chemoradiotherapy administered after local excision

4-12 weeks after local excision

Regular visits for chemoradiotherapy

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Every 3 months for 3 years, then every 2 months for 2 years

What Are the Treatments Tested in This Trial?

Interventions

• FOLFOX regimen

Trial Overview The study tests a neoadjuvant chemotherapy regimen called FOLFOX followed by local excision and post-operative chemoradiotherapy to see if patients can avoid more invasive surgery. The success of this approach will be measured by the number of patients able to undergo successful local excision without disease progression.

How Is the Trial Designed?

Group I: Neoadjuvant chemotherapy Experimental Treatment 1 Intervention

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

Approved in European Union as FOLFOX for:

• Colorectal cancer

Approved in United States as FOLFOX for:

• Colorectal cancer

Approved in Canada as FOLFOX for:

• Colorectal cancer

Approved in Japan as FOLFOX for:

• Colorectal cancer

Who Is Running the Clinical Trial?

Fox Chase Cancer Center

Lead Sponsor

Trials

236

Recruited

39,300+

Published Research Related to This Trial

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]

The modified mFOLFOX-4 regimen combined with radiotherapy showed a 3-year disease-free survival rate of 67.5% and an overall survival rate of 77.3% in 55 patients with stage III rectal adenocarcinoma, indicating its efficacy as an adjuvant treatment.

The treatment was generally well tolerated, with 92.7% of patients completing the planned chemotherapy cycles, although some experienced significant toxicities such as diarrhea (21.8%) and neutropenia (9.1%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant modified FOLFOX-4 in patients with stage III rectum adenocarcinoma. Cihan, Ş., Uncu, D., Babacan, NA., et al.[2017]

In a study of 82 patients with locally advanced rectal cancer, the mFOLFOX6 chemotherapy regimen was found to be safe, with low rates of severe adverse reactions such as Grade 4 neutropenia and catheter-related infections (both 2.4%).

Post-chemotherapy, 86.8% of patients showed a partial response, and significant reductions in tumor stages were observed, indicating that mFOLFOX6 is an effective preoperative treatment strategy that can lead to successful surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of preoperative mFOLFOX6 regimen chemotherapy for locally resectable advanced rectal cancer. Liu, L., Jiang, Z.[2021]

In a study of 40 colorectal cancer patients who underwent potentially curative metastasectomy, those treated with modified FOLFOX6 (mFOLFOX6) showed a trend towards longer relapse-free survival (28.5 months) compared to those treated with oral fluoropyrimidines (14.8 months), although this was not statistically significant (p=0.11).

The overall survival rates were similar between the mFOLFOX6 group (37.9 months) and the fluoropyrimidine group (31.3 months), indicating that while mFOLFOX6 may help delay relapse, it does not significantly improve overall survival compared to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Adjuvant chemotherapy comprising modified FOLFOX6 after curative resection of synchronous or metachronous metastasis from colorectal cancer]. Hatano, S., Ishibashi, K., Amano, K., et al.[2013]

In a study of 124 colorectal cancer patients treated with the mFOLFOX6 regimen, the most common severe adverse events were neutropenia (40%) and leucopenia (16%), indicating that while the treatment can have significant side effects, it is generally tolerable.

The incidence of adverse events in this Japanese cohort was similar or lower than those reported in Western countries, suggesting that the mFOLFOX6 regimen is manageable in clinical practice and that informed consent forms were updated to better inform patients about potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Revision of the informed consent form for patients based on investigation of adverse events of mFOLFOX6 regimen]. Kato, T., Matsunaga, Y., Motokawa, S., et al.[2013]

In a phase II study involving 48 patients with unresectable or metastatic colorectal cancer, an alternating regimen of mFOLFOX6 and FOLFIRI resulted in a promising overall response rate of 58.7% and a median overall survival of 28.4 months.

The treatment was well tolerated, with a low incidence of severe neurotoxicity (0%) and manageable adverse events, indicating a favorable safety profile for this chemotherapy approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of alternating mFOLFOX6 and FOLFIRI regimens in the first-line treatment for unresectable or metastatic colorectal cancer (KSCC0701). Oki, E., Emi, Y., Akagi, Y., et al.[2014]

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. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.3599

A randomized phase II study (OPTICAL2). Results: From July 2023 to August 2024, 123 patients with LACRC were enrolled, with 41 patients in each group, including 22 colon cancer and 101 ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2949819823000043

Individualizing multi-modality therapy for locally advanced ... Outcomes for patients with locally advanced disease have improved considerably with combined modality therapy with 5-year survival upwards of 75%, and distant ...

5. mskcc.org mskcc.org/news/folfox-rectal-cancer-treatment-without-radiation-new-option

Rectal Cancer Treatment Without Radiation: A New Option Preliminary research showed that giving FOLFOX before surgery could also have good results, which Dr. Schrag confirmed in a pilot trial. She ...

6. asco.org asco.org/abstracts-presentations/ABSTRACT127855

Neoadjuvant mFOLFOX6 for stage II/III rectal cancer ... Conclusions: Neoadjuvant therapy using mFOLFOX6 is a safe and efficacious treatment option for rectal cancer, especially locally advanced disease. Clinical ...

7. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-020-07766-5

Randomized phase II study comparing the efficacy and safety ... The surgical completion rate was 98.1% overall, 100% in the SOX arm, and 96.0% in the mFOLFOX6 arm. The incidences of pathological response ...