Chemoradiation and Surgery vs Non-Operative Management for Rectal Cancer

Not currently recruiting at 28 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Experimental therapies

Disqualifiers: Recurrent cancer, Unresectable cancer, Thrombotic events, 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: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether different treatment combinations can improve outcomes for people with locally advanced rectal cancer. Participants will receive treatments including chemotherapy (such as Capecitabine, also known as Xeloda, and Oxaliplatin), radiation (such as Intensity Modulated Radiotherapy, or IMRT), or a combination of both. Some groups will undergo surgery, while others will not. The goal is to determine which approach helps patients live longer without cancer returning. Those diagnosed with rectal cancer that hasn’t spread and who have not had prior pelvic radiation or chemotherapy might be a good match for this trial. As a Phase 2 trial, this research focuses on measuring how well the treatment works in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications. However, you cannot take any other experimental cancer therapies while participating. If you are on stable doses of anticoagulant therapy, you may continue those medications.

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

Research has shown that the FOLFOX treatment, which includes oxaliplatin, fluorouracil (5-FU), and leucovorin, is usually well-tolerated but can cause some side effects. Common issues include a low white blood cell count and nerve damage that causes tingling or numbness. Despite these side effects, the FDA has approved these drugs for colorectal cancer, indicating general safety.

The CapeOX treatment, combining capecitabine and oxaliplatin, shows similar safety results. The most common side effects are nerve damage and blood-related issues like anemia (a low red blood cell count). Some patients find it difficult to complete the full treatment due to these side effects.

For 5-fluorouracil (5-FU) alone, studies have shown it does not significantly increase the risk of major heart problems, suggesting safety for heart health.

Additionally, intensity-modulated radiotherapy (IMRT), a type of radiation treatment, causes fewer bowel side effects compared to older methods, making it a safer option for many patients receiving radiation for rectal cancer.

In summary, while all these treatments can cause side effects, they are generally considered safe and have been used successfully to treat colorectal cancer. Patients should consult their doctors to understand the potential risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for rectal cancer, which typically involve a sequential approach of surgery followed by chemoradiation, this trial explores the sequence of chemoradiation and chemotherapy with or without surgery. Researchers are excited about these treatments because they aim to optimize the timing and combination of chemotherapy and radiation. The induction neoadjuvant chemotherapy arm (INCT) starts with chemotherapy to shrink tumors before radiation, possibly minimizing surgical needs. Meanwhile, the consolidation neoadjuvant chemotherapy arm (CNCT) begins with chemoradiation, potentially making subsequent chemotherapy more effective. Both strategies explore the possibility of avoiding surgery, which can be invasive and challenging for patients, potentially leading to improved outcomes and quality of life.

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

Research has shown that the FOLFOX treatment, a combination of oxaliplatin, fluorouracil, and leucovorin, helps patients with locally advanced rectal cancer live longer without recurrence. One study found that 71.6% of patients treated with FOLFOX were disease-free after three years, compared to 62.9% of those who received a different chemotherapy. In this trial, participants in the INCT arm will receive FOLFOX as part of their treatment regimen. The CapeOX treatment, which includes capecitabine and oxaliplatin, also offers significant benefits and is part of the regimen for participants in both the INCT and CNCT arms. While CapeOX is effective, some patients may not complete all treatment cycles. Both FOLFOX and CapeOX are promising options for treating rectal cancer, with research supporting their ability to improve patient outcomes. ^{6 7 8 9 10}

Who Is on the Research Team?

Julio Garcia Aguilar, MD, PhD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with locally advanced rectal cancer who haven't had previous treatments like chemotherapy, surgery, or pelvic radiation. They should be generally healthy without active infections and no history of certain cancers in the past 5 years. Women must not be pregnant and agree to use contraception.

Inclusion Criteria

Patients must read, agree to, and sign a statement of Informed Consent prior to participation in this study. Patients who do not read or understand English are eligible and may be consented according to institutional and federal regulations.

ANC > 1.5 cells/mm3, HGB > 8.0 gm/dl, PLT > 150,000/mm3 total bilirubin ≤ 1.5 x ULN (except in patients with Gilbert's Syndrome who must have total bilirubin ≤ 3.0 x ULN), AST≤ 3 x ULN, ALT ≤ 3 x ULN.

My cancer is at Stage II or III according to MRI results.

Exclusion Criteria

I have had a heart attack, stroke, or severe chest pain in the last 6 months.

I am not currently on any other cancer treatments or experimental drugs.

Creatinine level greater than 1.5 times the upper limit of normal.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Neoadjuvant Chemotherapy

Participants receive 8 cycles of FOLFOX or 5 cycles of CapeOX over approximately 15-16 weeks

15-16 weeks

Endoscopic exam 2-4 weeks after chemotherapy

Chemoradiation

Participants receive chemoradiation therapy with either 5-FU or capecitabine for 6 weeks

6 weeks

Endoscopic exam 2-4 weeks after chemoradiation

Consolidation Neoadjuvant Chemotherapy

Participants receive 8 cycles of FOLFOX or 6 cycles of CapeOX following chemoradiation

Duration not specified

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

What Are the Treatments Tested in This Trial?

Interventions

• 5-Fluorouracil (5-FU)
• Capecitabine
• DRE-Endoscopy
• Intensity Modulated Radiotherapy (IMRT)
• Leucovorin
• Oxaliplatin

Trial Overview The study tests if a complete treatment before surgery (TNT) followed by either total mesorectal excision (TME) or non-operative management (NOM) improves disease-free survival over standard chemoradiation therapy plus TME and additional chemotherapy.

How Is the Trial Designed?

Group I: INCT Experimental Treatment 7 Interventions

Arm 1 will receive chemotherapy before chemoradiation. This is called induction neoadjuvant chemotherapy arm (INCT). The neoadjuvant chemotherapy regimen is prescribed specifically as 8 cycles of FOLFOX or 5 cycles of CapeOX over a period of approximately 15-16 weeks. Endoscopic exam (2-4 wks) after chemotherapy. If stable or response then pt will have radiation with either 5-FU or capecitabine.

Group II: CNCT Experimental Treatment 7 Interventions

Arm 2 will receive chemoradiation before chemotherapy This is called the consolidation neoadjuvant chemotherapy arm (CNCT). Pt will have 6 weeks of chemoradiation therapy. Along with the radiation the pt will receive either 5-FU or capecitabine. 2-4 weeks after pt will have endoscopic exam and if stable or response pt will have will have 8 cycles of FOLFOX or 6 cycles of CapeOX.

Capecitabine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in United States as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in Canada as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in Japan as Xeloda for:

• Colorectal cancer
• Breast cancer

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Medstar Health Research Institute

Collaborator

Trials

202

Recruited

187,000+

St. Joseph, Florida

Collaborator

Trials

1

Recruited

360+

University of Vermont

Collaborator

Trials

283

Recruited

3,747,000+

John Muir Health

Collaborator

Trials

3

Recruited

550+

Colon and Rectal Surgery Inc.

Industry Sponsor

Trials

1

Recruited

360+

The Cleveland Clinic

Collaborator

Trials

1,072

Recruited

1,377,000+

University of Chicago

Collaborator

Trials

1,086

Recruited

844,000+

University of South Florida

Collaborator

Trials

433

Recruited

198,000+

University of California, San Francisco

Collaborator

Trials

2,636

Recruited

19,080,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6946745/

Phase II study of capecitabine plus oxaliplatin (CapOX) as ... However, the efficacy and safety of oxaliplatin-based adjuvant chemotherapy for locally advanced rectal cancer remain unclear.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.3_suppl.90

Real-world assessment of capecitabine and oxaliplatin ... Among patients intended to receive 4 cycles of CAPOX, only 57% (37/65) completed all 4 cycles. Female patients were less likely to complete ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39993118/

Evaluation of the effectiveness of using capecitabine ... The purpose of this study was to assess and compare the clinical effectiveness of capecitabine monotherapy and that of capecitabine combined with oxaliplatin.

4. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-024-12972-6

CapeOX as neoadjuvant chemotherapy for locally advanced ... CapeOX NAC presents notable benefits for LARC patients and its clinical significance may be underestimated. The NAR score demonstrates superior prognostic ...

5. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2786689

Postoperative Chemoradiotherapy With Capecitabine and ... This randomized clinical trial examines the efficacy and toxic effects of postoperative capecitabine vs oxaliplatin plus capecitabine with ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11639909/

Long-Term Outcomes of 5-Fluorouracil-Related Early-Onset ... The median overall survival was 2.5 years in those who experienced early-onset toxicity from 5-FU during their first FOLFOX/FOLFIRINOX cycle.

7. cardiooncologyjournal.biomedcentral.com cardiooncologyjournal.biomedcentral.com/articles/10.1186/s40959-024-00294-2

Cardiovascular safety of 5-fluorouracil and capecitabine in ... Fluoropyrimidine use in patients with colorectal carcinoma did not increase the risk of MACE, cardiovascular death, or other specific cardiovascular conditions.

8. nejm.org nejm.org/doi/full/10.1056/NEJMoa2303269

Preoperative Treatment of Locally Advanced Rectal Cancer Five-year disease-free survival was 80.8% (95% CI, 77.9 to 83.7) in the FOLFOX group and 78.6% (95% CI, 75.4 to 81.8) in the chemoradiotherapy ...

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0959804914009125

Association of adverse events and survival in colorectal ... With 5FU based adjuvant therapy overall survival benefit of 7–15% was achieved in stage III patients translating into 22–34% decrease in relative risk of death ...

10. clinicaltrials.gov clinicaltrials.gov/study/NCT07042685

Study Details | NCT07042685 | Trial of 5-Fluorouracil (5FU) ... This is a phase II trial investigating the efficacy and safety of 5-Fluorouracil (5FU)-based therapy in combination with fruquintinib for patients with locally ...