Radiation + Chemotherapy for Rectal Cancer

(NOM-ERA Trial)

Not currently recruiting at 4 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of combining radiation and chemotherapy for treating rectal cancer that hasn't spread. Researchers aim to determine if this approach can achieve a high rate of complete clinical response, meaning no signs of cancer remain. Participants will receive one of two treatment plans: radiation with a chemotherapy regimen called FOLFOX, or radiation with a different regimen called CAPOX. Candidates for this trial include those diagnosed with rectal cancer located within 12 cm of the anal verge who haven't undergone prior treatments like radiation or chemotherapy. As an unphased trial, this study provides a unique opportunity to explore innovative treatment combinations for rectal cancer.

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.

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

A previous study found that combining radiation therapy with the drugs capecitabine and oxaliplatin (CAPOX) effectively treated rectal cancer. Most patients tolerated this treatment well, experiencing no severe problems. Another study confirmed that this combination was safe and effective in treating the cancer.

Research on radiation plus FOLFOX also shows promising results. Patients experienced fewer issues like tiredness and nerve pain compared to other treatments. Overall, the FOLFOX combination was manageable for most people.

Both treatment options have been used before, and studies suggest they are safe for people with rectal cancer. While side effects can occur, they are usually not severe for most patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for rectal cancer because they combine radiation with powerful chemotherapy regimens, FOLFOX and CAPOX, to potentially enhance treatment effectiveness. Unlike the traditional approach of sequential therapy, these regimens integrate radiation with chemotherapy, which may improve targeting and destruction of cancer cells more effectively. The CAPOX regimen includes capecitabine, an oral medication that offers convenience over intravenous options, and both regimens allow for an optional radiation boost directly to the primary tumor, which could improve local control of the disease. This innovative combination and timing could lead to better outcomes and reduced recurrence rates for rectal cancer patients.

What evidence suggests that this trial's treatments could be effective for rectal cancer?

This trial will compare two treatment options for rectal cancer: Radiation combined with the CAPOX regimen and Radiation combined with the FOLFOX regimen. Research has shown that combining radiation therapy with chemotherapy, such as the CAPOX regimen, holds promise for treating rectal cancer. Studies have found that using capecitabine and oxaliplatin with radiation can effectively shrink tumors before surgery. This method has proven practical and has shown positive results in reducing the size and spread of cancer.

For the FOLFOX regimen, combining radiation with this chemotherapy has also yielded good results. One study found that 86% of patients had a complete clinical response (cCR), meaning the cancer was not detectable after treatment. This combination has been effective in improving survival rates and controlling the tumor locally. Both treatment options in this trial show promise in effectively managing rectal cancer. ^{2 6 7 8 9}

Who Is on the Research Team?

Michael Waters, M.D., Ph.D.

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Radiation + FOLFOX Experimental Treatment 2 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 * An optional simultaneous integrated boost of 30 Gy in 5 fractions to the primary tumor is permitted

Group II: Radiation + CAPOX Experimental Treatment 2 Interventions

* Pelvic radiotherapy 5GY x 5 fractions once daily * Radiation to extra-mesorectal node 7 Gy x 5 fractions once daily * CAPOX should begin 2-4 weeks after completion of radiotherapy and will consist of CAPOX x 5 cycles (15 weeks). * Capecitabine 1000 mg/m\^2 by mouth twice per day on days 1-14 of every 21 day cycle * Oxaliplatin 130 mg/m\^2 intravenous on day 1 of each 21 day cycle * 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+

Published Research Related to This Trial

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 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 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 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]

Citations

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Capecitabine, Oxaliplatin, and Radiation Therapy in ... This phase II trial is studying how well giving capecitabine and oxaliplatin together with radiation therapy works in treating patients who are undergoing ...

2. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)47809-5/fulltext

Phase II study of preoperative oxaliplatin, capecitabine and ... Conclusions: Combination of preoperative radiotherapy with capecitabine and oxaliplatin is feasible for downstaging rectal cancer. Keywords. capecitabine ...

3. practicalradonc.org practicalradonc.org/article/S1879-8500(24)00304-7/fulltext

Radiation Therapy for Rectal Cancer: An ASTRO Clinical ... With the results of several recently published clinical trials, this guideline focused update provides evidence-based recommendations for the indications ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0923753419478095

Phase II study of preoperative oxaliplatin, capecitabine and ... Conclusions: Combination of preoperative radiotherapy with capecitabine and oxaliplatin is feasible for downstaging rectal cancer. Previous article in issue

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Efficacy Endpoints of Radiation Therapy Group Protocol 0247 Median follow-up for RT with capecitabine/irinotecan arm was 3.77 years and for RT with capecitabine/oxaliplatin arm was 3.97 years. Four-year DFS, OS, LRF, DF, ...

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Phase II study of preoperative oxaliplatin, capecitabine and ... Conclusions: Combination of preoperative radiotherapy with capecitabine and oxaliplatin is feasible for downstaging rectal cancer. Publication types. Clinical ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2405630825001065

Review Article Radiotherapy boost to the primary tumour in ... Although a radiotherapy (RT) boost to the primary tumour may enhance CR rates, clear guidelines are currently lacking. This systematic review and meta-analysis ...

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Bevacizumab, Oxaliplatin, and Capecitabine With ... Conclusions: The combination of bevacizumab, capecitabine, oxaliplatin, and radiation therapy in rectal cancer was tolerable, with encouraging response rates.

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Capecitabine and Timing of Radiotherapy During ... Large randomized trials in metastatic colorectal cancer have shown that capecitabine treatment leads to a superior response rate and safety profile, as well as ...