FOLFOX Chemotherapy for Rectal Cancer

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

12 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the FOLFOX treatment for rectal cancer?

Research shows that adding oxaliplatin to the FOLFOX regimen improves disease-free survival in colorectal cancer, and postoperative FOLFOX chemotherapy combined with radiation can improve survival and local tumor control in rectal cancer. ^{1 2 3 4 5}

Is FOLFOX chemotherapy generally safe for humans?

FOLFOX chemotherapy, used for colorectal cancer, has been studied for safety in various patient groups. It can cause side effects like blood-related issues (low blood cell counts) and digestive problems (nausea, diarrhea), especially in elderly patients or those with poor health. However, it is generally considered safe when monitored by healthcare professionals. ^{6 7 8 9 10}

How is the FOLFOX drug unique for treating rectal cancer?

FOLFOX is a combination chemotherapy regimen that includes folinic acid, fluorouracil, and oxaliplatin, and is used to treat rectal cancer by enhancing response rates and patient survival. It is unique because it can be used preoperatively to improve long-term outcomes and has shown effectiveness even in advanced cases, although it may cause side effects like peripheral neuropathy and interstitial pneumonia. ^{3 11 12 13 14}

What is the purpose of this trial?

The purpose of this study is to evaluate the treatment of patients with locally advanced rectal cancer for complete response to neoadjuvant chemotherapy without the use of radiation and surgery.

Research Team

Richard Dunne, MD

Principal Investigator

University of Rochester

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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 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]

References

1. France pubmed.ncbi.nlm.nih.gov

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

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

Current status of adjuvant therapy for colorectal cancer. [2015]

3. France pubmed.ncbi.nlm.nih.gov

Chemotherapy of metastatic colorectal cancer. [2013]

4. Thailand pubmed.ncbi.nlm.nih.gov

Serum miR-19a predicts resistance to FOLFOX chemotherapy in advanced colorectal cancer cases. [2019]

5. Italy pubmed.ncbi.nlm.nih.gov

A randomized phase II study to compare oxaliplatin plus 5-fluorouracil and leucovorin (FOLFOX4) versus oxaliplatin plus raltitrexed (TOMOX) as first-line chemotherapy for advanced colorectal cancer. [2021]

6. Switzerland 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. [2022]

7. Canada 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. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Multicenter safety study of mFOLFOX6 for unresectable advanced/recurrent colorectal cancer in elderly patients. [2021]

9. Japan pubmed.ncbi.nlm.nih.gov

[Safety and efficacy analysis of FOLFOX4 regimen in elderly compared to younger colorectal cancer patients]. [2013]

10. England 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? [2014]

11. England pubmed.ncbi.nlm.nih.gov

Prognosis and treatment of FOLFOX therapy related interstitial pneumonia: a plea for multimodal immune modulating therapy in the respiratory insufficient patient. [2022]

12. Japan pubmed.ncbi.nlm.nih.gov

The survival impact of preoperative FOLFOX for resectable locally advanced rectal cancer: the R-NAC-01 study. [2022]

13. England pubmed.ncbi.nlm.nih.gov

FOLFOX4 versus sequential dose-dense FOLFOX7 followed by FOLFIRI in patients with resectable metastatic colorectal cancer (MIROX): a pragmatic approach to chemotherapy timing with perioperative or postoperative chemotherapy from an open-label, randomized phase III trial. [2022]

14. Japan pubmed.ncbi.nlm.nih.gov

[A CR case of colorectal cancer given 39 courses of FOLFOX]. [2015]