Radiation + Chemotherapy for Rectal Cancer

(NOM-ERA Trial)

Recruiting at 3 trial locations

Overseen By Hyun Kim

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Washington University School of Medicine

Must not be taking: Oxaliplatin, Capecitabine, Investigational agents

Disqualifiers: Prior radiation, Other malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 13

63 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a combination of radiation therapy and chemotherapy for patients with rectal cancer that hasn't spread. The goal is to see if this treatment can effectively shrink and eliminate the cancer without surgery. This approach has shown potential benefits in treatment compliance and outcomes.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on investigational agents or have had prior use of certain cancer drugs like oxaliplatin or capecitabine, you may not be eligible to participate.

What data supports the effectiveness of the treatment Radiation + Chemotherapy for Rectal Cancer?

Research shows that using a combination of mFOLFOX6 chemotherapy and radiotherapy can lead to a higher rate of complete tumor response in patients with locally advanced rectal cancer compared to using fluorouracil and radiotherapy alone. ^{1 2 3 4 5}

Is the combination of radiation and chemotherapy safe for rectal cancer treatment?

The mFOLFOX6 chemotherapy regimen, often used for colorectal cancer, has been studied for safety. Common side effects include low white blood cell counts, anemia, nausea, and fatigue, but it is generally considered tolerable in clinical practice. Adjustments like omitting certain drug doses can help reduce some side effects. ^{1 6 7 8 9}

How is the treatment of radiation plus FOLFOX chemotherapy unique for rectal cancer?

This treatment combines radiation therapy with the FOLFOX chemotherapy regimen, which includes drugs like 5-fluorouracil, oxaliplatin, and leucovorin, to enhance the effectiveness of preoperative treatment for rectal cancer. It has shown promising results in improving the complete response rate and quality of life for patients compared to other regimens. ^{1 2 3 10 11}

Research Team

Hyun Kim

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

This trial is for adults with stage I-IIIB non-metastatic rectal adenocarcinoma, confirmed by biopsy and MRI. Participants must have an ECOG performance status of 0-2, adequate blood cell counts, a detectable tumor not more than 12 cm from the anal verge, and agree to use contraception if applicable. Exclusions include prior treatments for rectal cancer, other recent malignancies (except certain skin cancers), uncontrolled illnesses like heart failure or infection, HIV with low CD4+ count or recent opportunistic infections.

Inclusion Criteria

Platelets >100,000 cells/mm3

I am able to care for myself and perform daily activities.

Able to understand and willing to sign an Institutional Review Board (IRB)-approved written informed consent document.

Exclusion Criteria

I have not had radiation therapy to my pelvic area.

I do not have any serious illnesses like heart failure or uncontrolled infections.

I have been treated with oxaliplatin or capecitabine for cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive short course radiation therapy (SCRT) with pelvic radiotherapy and optional integrated boost

1 week

5 visits (in-person)

Chemotherapy

Participants receive FOLFOX or CAPOX chemotherapy following radiation

15-16 weeks

8 visits (in-person) for FOLFOX or 5 visits (in-person) for CAPOX

Follow-up

Participants are monitored for safety and effectiveness after treatment

10-14 months

Treatment Details

Interventions

• Blood for ctDNA
• FOLFOX regimen
• Radiation therapy
• Rectal biopsy samples

Trial Overview The study tests short course radiation therapy followed by FOLFOX chemotherapy in patients with rectal cancer who are not undergoing surgery. The goal is to validate the complete clinical response rate observed in earlier research. Patients' responses will be monitored using biopsies, blood tests for circulating tumor DNA (ctDNA), and quality-of-life assessments through the FACT-C questionnaire.

Participant Groups

Group I: Radiation + FOLFOX Experimental Treatment 5 Interventions

* Pelvic radiotherapy 5GY x 5 fractions once daily * Radiation to extra-mesorectal node 7 Gy x 5 fractions once daily * FOLFOX should begin 2-4 weeks after completion of radiotherapy and will consist of FOLFOX x 8 cycles (16 weeks). * Oxaliplatin day 1 every 14 days * Leucovorin day 1 every 14 days. Levoleucovorin may be substituted if leucovorin is not available. * 5-FU bolus day 1 every 14 days * 5-FU infusion day 1 every 14 days over 46 hours * Alternatively CAPOX (capecitabine and oxaliplatin) may be given for 5 cycles over 15 weeks. * An optional simultaneous integrated boost of 30 Gy in 5 fractions to the primary tumor is permitted

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?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Findings from Research

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 phase 2 trial involving 80 patients with rectal adenocarcinoma, short-course radiation therapy followed by mFOLFOX6 chemotherapy resulted in stable quality of life (QOL) outcomes one year after treatment, indicating that the regimen is well-tolerated by patients.

Patients with an ostomy reported significantly lower functional well-being and colorectal cancer-specific quality of life compared to those without an ostomy, highlighting the impact of surgical outcomes on patient experiences post-treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality of Life Outcomes From a Phase 2 Trial of Short-Course Radiation Therapy Followed by FOLFOX Chemotherapy as Preoperative Treatment for Rectal Cancer. Khwaja, SS., Roy, A., Markovina, S., et al.[2022]

In a study of 106 patients with locally advanced rectal cancer, neoadjuvant modified FOLFOXIRI chemotherapy combined with selective radiotherapy resulted in a 3-year disease-free survival rate of 78.9%, which is significantly better than historical controls receiving chemoradiotherapy.

Patients treated with mFOLFOXIRI experienced a lower incidence of anastomotic fistula (5.5%) compared to those receiving chemoradiotherapy (17.8%), indicating a potential safety advantage of this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant Modified FOLFOXIRI With Selective Radiotherapy in Locally Advanced Rectal Cancer: Long-term Outcomes of Phase II Study and Propensity-Score-Matched Comparison With Chemoradiotherapy. Zhang, J., Li, J., Huang, M., et al.[2023]

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 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]

References

1. Thailand pubmed.ncbi.nlm.nih.gov

Adjuvant modified FOLFOX-4 in patients with stage III rectum adenocarcinoma. [2017]

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

Quality of Life Outcomes From a Phase 2 Trial of Short-Course Radiation Therapy Followed by FOLFOX Chemotherapy as Preoperative Treatment for Rectal Cancer. [2022]

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

Neoadjuvant Modified FOLFOX6 With or Without Radiation Versus Fluorouracil Plus Radiation for Locally Advanced Rectal Cancer: Final Results of the Chinese FOWARC Trial. [2020]

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

Neoadjuvant Modified FOLFOXIRI With Selective Radiotherapy in Locally Advanced Rectal Cancer: Long-term Outcomes of Phase II Study and Propensity-Score-Matched Comparison With Chemoradiotherapy. [2023]

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

Effect of Primary Tumor Side on Survival Outcomes in Untreated Patients With Metastatic Colorectal Cancer When Selective Internal Radiation Therapy Is Added to Chemotherapy: Combined Analysis of Two Randomized Controlled Studies. [2019]

6. England pubmed.ncbi.nlm.nih.gov

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

7. Japan pubmed.ncbi.nlm.nih.gov

[Revision of the informed consent form for patients based on investigation of adverse events of mFOLFOX6 regimen]. [2013]

8. 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]

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

Effects of reduced dose intensity of modified FOLFOX6 in patients with metastatic or recurrent colorectal cancer. [2019]

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

Capecitabine and oxaliplatin in the preoperative multimodality treatment of rectal cancer: surgical end points from National Surgical Adjuvant Breast and Bowel Project trial R-04. [2022]

11. Japan pubmed.ncbi.nlm.nih.gov

[A Case of Effective Chemoradiotherapy Using mFOLFOX6 for Locally Advanced Rectal Cancer]. [2018]