Chemotherapy + Radiation for Rectal Cancer

Recruiting at 2 trial locations

Overseen By Carrie Donovan, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Virginia Commonwealth University

Disqualifiers: Cardiac disease, Infection, Inflammatory bowel, 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

Compensation: Varies

Number of Visits: 13

54 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of combining chemotherapy (using a drug mix called mFOLFOX) with short-course radiation for treating surgically removable rectal cancer. The goal is to determine if this treatment can shrink tumors, enhancing the effectiveness of surgery. The trial seeks participants diagnosed with rectal cancer that has not spread and who are candidates for surgery. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that mFOLFOX, a combination of three drugs (5-fluorouracil, leucovorin, and oxaliplatin), is generally well-tolerated. The FDA has already approved these drugs for treating colorectal cancer. Studies indicate that adding oxaliplatin improves results without causing severe side effects.

For short-course radiation therapy, research indicates it is safe for rectal cancer patients. Some patients may experience mild side effects, such as diarrhea, but these are usually manageable. Studies also show that this treatment has fewer complications compared to other methods.

Overall, both treatments have good safety records, with side effects that are generally manageable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for rectal cancer involve lengthy courses of chemotherapy followed by radiation, which can take several weeks or even months to complete. However, this new treatment combines mFOLFOX chemotherapy with short-course radiation therapy, potentially speeding up the process significantly. Researchers are excited because the radiation is delivered in just 5 days using intensity-modulated radiation therapy (IMRT), which precisely targets the cancer while sparing healthy tissue. Additionally, the chemotherapy regimen is structured to both precede and follow the radiation, which may enhance its effectiveness and provide a more comprehensive attack on cancer cells. This approach could lead to quicker treatment times and potentially better outcomes for patients.

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

Research shows that mFOLFOX, a mix of chemotherapy drugs, helps rectal cancer patients live longer without disease progression. Studies have found that adding oxaliplatin to fluorouracil and leucovorin doubles the response rate and extends the time before cancer progresses, allowing patients a longer period without worsening cancer.

Short-course radiation therapy (SCRT) has also proven effective for rectal cancer, providing good long-term results with fewer harmful side effects. SCRT matches the effectiveness of longer radiation treatments and is more cost-effective.

In this trial, participants will receive a combination of these treatments, with mFOLFOX chemotherapy administered before and after short-course radiation therapy. Together, these treatments have shown promise in effectively managing rectal cancer and improving patients' chances of recovery. ^{6 7 8 9 10}

Who Is on the Research Team?

Khalid Matin

Principal Investigator

Massey Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with resectable rectal cancer, without distant metastases. Participants must have adequate organ function and no serious recent illnesses or surgeries. They should not be pregnant or breastfeeding and must agree to use birth control during the study.

Inclusion Criteria

I am fully active and can carry on all pre-disease activities without restriction.

My cancer is in an advanced local stage but hasn't spread to distant parts.

I was diagnosed with rectal cancer in the last 3 months.

Exclusion Criteria

My cancer has spread to distant parts of my body.

You have a health, mental, or social condition that may make it more risky for you to participate in the study or make it difficult for you to follow the study's requirements.

I have liver problems causing jaundice or blood clotting issues.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemotherapy

Participants receive 4 cycles of systemic chemotherapy with mFOLFOX6 before CRT starts

8 weeks

4 visits (in-person)

Radiation

Participants undergo short-course pelvic IMRT with concurrent continuous infusion of 5-FU

1 week

5 visits (in-person)

Consolidation Chemotherapy

Participants receive 4 additional cycles of systemic chemotherapy with mFOLFOX6 after CRT ends

8 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

What Are the Treatments Tested in This Trial?

Interventions

• mFOLFOX
• Short-course Radiation Therapy

Trial Overview The trial tests a combination of chemotherapy (mFOLFOX) and short-course radiation therapy as initial treatment before surgery in patients with rectal cancer. It's designed to see if this approach is effective in treating the disease.

How Is the Trial Designed?

Group I: Concurrent Chemotherapy/ Radiation Therapy Experimental Treatment 2 Interventions

5-Fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) four 14-day cycles will be given before CRT starts. Pelvic Intensity-modulated radiation therapy (IMRT): 25 Gy in 5 fractions over 5 days + Continuous infusion 5-fluorouracil (5-FU) for 4 days (96 hours) followed by four 14-day cycles of (mFOLFOX6) to be given after CRT ends.

Who Is Running the Clinical Trial?

Virginia Commonwealth University

Lead Sponsor

Trials

732

Recruited

22,900,000+

Published Research Related to This Trial

Short-course radiation followed by early surgery provides similar oncologic outcomes as long-course chemoradiation for patients with locally advanced rectal cancer, making it a viable treatment option.

Delaying surgery after short-course radiation can reduce post-operative complications and allows for the administration of neoadjuvant systemic therapy, which may enhance tumor response and lower the risk of distant relapses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant Short-Course Radiation Therapy for Rectal Cancer: Trends and Controversies. Narang, AK., Meyer, J.[2019]

In a study of 36 patients with oligometastatic rectal cancer, 17% achieved a clinical complete response (cCR) after treatment with short-course radiation therapy combined with chemotherapy (SCRT-CTX), indicating potential efficacy of this nonoperative approach.

The overall survival rate was 83% at 12 months and 57% at 24 months, with longer chemotherapy duration and definitive treatment of metastatic sites associated with improved survival outcomes, while hospitalization rates for complications were relatively low.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oligometastatic Rectal Adenocarcinoma Treated With Short-Course Radiation Therapy and Chemotherapy With Nonoperative Intent of the Primary for Locoregional Complete Responders. Schiff, JP., Chin, RI., Roy, A., et al.[2022]

In a study of 32 patients with locally advanced rectal cancer and liver-only metastases, the combination of mFOLFOX6 chemotherapy followed by short-course radiotherapy (SCRT) was effective, achieving a complete surgical resection (R0) in 63% of patients.

The treatment regimen was safe, with only one patient discontinuing due to toxicity and no treatment-related deaths, while the median overall survival was 38 months and progression-free survival was 9 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of preoperative mFOLFOX6 with short-course radiotherapy in patients with locally advanced rectal cancer and liver-only metastasis. Kim, KH., Shin, SJ., Cho, MS., et al.[2022]

In a study of 63 patients with locally advanced rectal cancer, short course neoadjuvant radiation (25 Gy in five fractions) resulted in a high R0 resection rate of 97% and a low local recurrence rate of only 5%.

The treatment demonstrated acceptable toxicity, with 18% of patients experiencing postoperative complications, while achieving 5-year overall and relapse-free survival rates of 71% and 69%, respectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-course preoperative radiation therapy for operable rectal cancer. Tankel, K., Hay, J., Ma, R., et al.[2019]

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]

The study demonstrated that hypofractionated, conformal radiation therapy (RT) at a dose of 50 Gy in 10 fractions is feasible and safe for treating patients with liver metastases, with no dose-limiting toxicities observed across all dose levels in a cohort of 26 patients.

While some patients experienced grade 3 toxicities, such as enteritis and lymphopenia, these were manageable and reversible, indicating that higher doses of radiation can be administered safely in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NRG Oncology/RTOG 0438: A Phase 1 Trial of Highly Conformal Radiation Therapy for Liver Metastases. Dawson, LA., Winter, KA., Katz, AW., et al.[2020]

In a phase II study involving 36 prostate cancer patients, a short course of hypofractionated radiotherapy (56 Gy in 16 fractions over 4 weeks) resulted in no severe (grade 3-4) side effects, indicating a favorable safety profile.

While early side effects were more common with hypofractionation (75% experienced grade 1-2 gastrointestinal and genitourinary toxicity) compared to conventional treatments, these side effects resolved within two months after treatment, suggesting that the regimen is manageable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of a four-week hypofractionated external beam radiotherapy regimen for prostate cancer: report on acute toxicity. Soete, G., Arcangeli, S., De Meerleer, G., et al.[2018]

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 clinical trial involving 19 patients with nonmetastatic rectal adenocarcinoma, short-course radiation therapy (SCRT) followed by chemotherapy achieved a high clinical complete response (cCR) rate of 68% at one year, indicating its efficacy as a nonoperative treatment option.

Patients who achieved cCR had significantly better 2-year disease-free survival (93% vs 67%) and overall survival (100% vs 67%) compared to those who did not, while maintaining intact anorectal function and experiencing no severe late effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonoperative Rectal Cancer Management With Short-Course Radiation Followed by Chemotherapy: A Nonrandomized Control Trial. Kim, H., Pedersen, K., Olsen, JR., et al.[2022]

Increasing the intensity of neoadjuvant therapy for rectal cancer, such as higher radiation doses or concurrent chemotherapy, may improve the rate of complete pathological responses, but careful patient selection is crucial for maximizing benefits.

Short-course radiotherapy (5 Gy × 5) is recommended for certain patients with T3 or N+ rectal cancer, while long-course chemoradiotherapy remains the standard for locally advanced cases, highlighting the need for individualized treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Radiotherapy standard and progress in locally advanced rectal cancer]. Shen, L., Zhang, Z.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11557790/

Long-term outcomes and prognostic factors of short-course ... SCRT is an effective treatment in patients with rectal cancer and provides good outcomes with very low rates of toxicity profile.

2. eymj.org eymj.org/pdf/10.3349/ymj.2023.0042

Short-Term Outcomes and Cost-Effectiveness between ... In addition, SCRT showed significant reduc- tion in the total cost of care and distinguished cost-effectiveness compared to LCRT. Key Words: ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0936655524004187

Early Outcomes of Preoperative Short Course ... Neoadjuvant short-course radiotherapy with simultaneous integrated boost for rectal cancer provides high pathological complete response rates with no increased ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.4_suppl.146

Short-course radiotherapy in rectal cancer: A single-center ... Results: 44 patients were treated with SCRT, 29 (66%) were male, with a median age of 59 years (46-73). Most of the patients had stage IV ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04370418?term=NCT00479583%20NCT00500292%20NCT00710736%20NCT00941499%20NCT00943137%20NCT00983541%20NCT01046864%20NCT01183663%20NCT01332604%20NCT01633970%20NCT01653470%20NCT01750918%20NCT02024607%20NCT02640365%20NCT02937116%20NCT03082209%20NCT03143153%20NCT03368859%20NCT04370418%20NCT04611724%20NCT05217069%20NCT05229497%20NCT05235542%20NCT05329766%20NCT05332002%20NCT05605509&rank=8

Neo-adjuvant Short Course Chemo-radiation Therapy in ... Two meta-analyses showed that short course is as effective as long course chemo-radiation in the management of locally advanced rectal cancer in the terms of ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10310334/

Short-course radiotherapy for rectal cancer - PubMed Central Surgery can safely be deferred after SCRT, allowing an opportunity to deliver chemotherapy (ChT) preoperatively rather than postoperatively [2, 3]. In cases of ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.3_suppl.92

A single-institution experience of acute toxicities in patients ... Conclusions: We have identified acute toxicities in patients treated with short course hypofractionated radiation, including diarrhea, rectal ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S2949819824000281

Efficacy and safety of short-course radiotherapy versus ... While the sequential order of LC-CRT and systemic chemotherapy did not influence DFS, patients treated with CNCT had higher chances to preserve the rectum (54% ...

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

Radiation Therapy for Rectal Cancer: An ASTRO Clinical ... Nonoperative rectal cancer management with short-course radiation followed by chemotherapy: a nonrandomized control trial. Clin Colorectal Cancer. 2021; 20 ...

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10232996/

Short-Term Outcomes and Cost-Effectiveness between ... SCRT was shown to be the dominant treatment option with fewer recurrences and fewer complications at a lower cost.