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

Trial Summary

What is the purpose of this trial?

This is phase 2 trial of neoadjuvant therapy and short-course radiotherapy in resectable rectal cancer.

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.

What data supports the effectiveness of the treatment mFOLFOX and short-course radiation therapy for rectal cancer?

Research shows that using short-course radiation therapy followed by mFOLFOX chemotherapy can improve local control of rectal cancer and maintain quality of life for patients. This combination has been effective in managing rectal cancer, even in cases with liver-only metastases. ^{1 2 3 4 5}

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

Studies have shown that the combination of mFOLFOX chemotherapy and short-course radiation therapy is generally safe for patients with rectal cancer, with research focusing on both quality of life and safety outcomes. Some studies also report on early side effects, which are important for understanding the treatment's safety profile. ^{1 3 6 7 8}

How is the treatment of mFOLFOX and short-course radiation therapy unique for rectal cancer?

This treatment combines a short-course radiation therapy (5 sessions of 5 Gy each) with mFOLFOX chemotherapy before surgery, which is different from the standard long-course chemoradiotherapy. It aims to reduce treatment time and improve patient tolerance while maintaining effectiveness. ^{1 2 5 9 10}

Research Team

Khalid Matin

Principal Investigator

Massey Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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 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]

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 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]

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]

References

1. 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]

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

Neoadjuvant Short-Course Radiation Therapy for Rectal Cancer: Trends and Controversies. [2019]

3. Ireland 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. [2022]

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

Short-course preoperative radiation therapy for operable rectal cancer. [2019]

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

Nonoperative Rectal Cancer Management With Short-Course Radiation Followed by Chemotherapy: A Nonrandomized Control Trial. [2022]

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

NRG Oncology/RTOG 0438: A Phase 1 Trial of Highly Conformal Radiation Therapy for Liver Metastases. [2020]

7. Ireland pubmed.ncbi.nlm.nih.gov

Phase II study of a four-week hypofractionated external beam radiotherapy regimen for prostate cancer: report on acute toxicity. [2018]

8. Thailand pubmed.ncbi.nlm.nih.gov

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

9. United States 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. [2022]

10. China pubmed.ncbi.nlm.nih.gov

[Radiotherapy standard and progress in locally advanced rectal cancer]. [2018]