Pre-operative Chemotherapy for Rectal Cancer

(RAPIDO Trial)

Not currently recruiting at 62 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: University Medical Center Groningen

Disqualifiers: Metastatic disease, Crohn's, Ulcerative colitis, Cardiac disease, 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)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach to treating rectal cancer before surgery. Instead of the usual long course of combined chemotherapy and radiation, it tests whether a shorter radiation course followed by chemotherapy can better prepare patients for surgery and improve survival rates. People with newly diagnosed, advanced rectal cancer that has grown into nearby tissues might be suitable candidates. The trial aims to determine if this method can effectively target the main tumor and any tiny spread of cancer, possibly leading to better outcomes compared to the standard treatment. As a Phase 3 trial, this treatment is in the final step before FDA approval, offering patients a chance to benefit from a potentially groundbreaking therapy.

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 have uncontrolled medical conditions or are taking investigational treatments for rectal cancer, you may not be eligible to participate.

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

Research has shown that a short course of radiotherapy combined with CAPOX (a type of chemotherapy) is generally safe for people with rectal cancer. In past studies, this treatment proved effective and had few side effects. Most patients tolerated the treatment well, and serious problems were uncommon, indicating that the treatment is usually safe. However, as with any treatment, risks remain, so discussing these with the trial team is important. ^{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 offer potentially more effective and quicker options compared to the standard long course chemoradiotherapy. The experimental approach combines a short course of radiotherapy (5x5Gy) followed by chemotherapy with CAPOX, aiming to shrink tumors more efficiently before surgery. This method could reduce treatment time and enhance the effectiveness of tumor reduction, providing patients with a faster path to surgery and potentially better outcomes.

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

This trial will compare two treatment approaches for rectal cancer. One arm involves a short course of radiotherapy combined with CAPOX chemotherapy before surgery. Studies have shown that this method is promising for treating rectal cancer, as it can reduce the risk of local recurrence by half. In some studies, the chance of the cancer returning locally dropped from 27% to as low as 5% with this treatment. Patients generally experienced good results with few side effects. This suggests that using short-course radiotherapy and chemotherapy before surgery might improve survival chances. ^{1 6 7 8 9}

Who Is on the Research Team?

B. van Etten, MD, PhD

Principal Investigator

University Medical Center Groningen, Department of Surgery, Groningen, The Netherlands

B. Glimelius, MD, PhD

Principal Investigator

Akademiska Sjukhuset, Department of Oncology, Uppsala, Sweden

G. A. Hospers, MD, PhD

Principal Investigator

University Medical Center Groningen, Department of Medical Oncology, Groningen, The Netherlands

C. J. van de Velde, MD, PhD

Principal Investigator

Leiden University Medical Center, Department of Surgery, Leiden, The Netherlands

C.A.M. Marijnen, MD, PhD

Principal Investigator

Netherlands Cancer Institute, Amsterdam, the Netherlands

P. Nilsson, MD, PhD

Principal Investigator

Karolinska Universitetssjukhuset, Stockholm, Sweden

Are You a Good Fit for This Trial?

This trial is for adults with newly diagnosed, high-risk rectal cancer that hasn't spread to distant parts of the body. Eligible patients must have certain tumor characteristics on MRI and can't be pregnant or breastfeeding, have uncontrolled medical conditions, significant heart disease, neuropathy symptoms, known malabsorption syndromes, or a history of other cancers within the last 5 years.

Inclusion Criteria

My cancer is advanced, affecting nearby organs or has spread to many lymph nodes.

My rectal cancer is newly diagnosed and confirmed by a biopsy.

Exclusion Criteria

I have a serious heart condition or had a heart attack in the last year.

My cancer has grown into the upper part of my sacrum or nerve roots, making surgery impossible.

I have a known DPD deficiency.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive short course 5x5 Gy radiation scheme

1 week

Chemotherapy

Participants receive six cycles of combination chemotherapy (capecitabine/5FU and oxaliplatin)

12-18 weeks

Surgery

Participants undergo TME surgery or more extensive surgery if required

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

What Are the Treatments Tested in This Trial?

Interventions

• chemotherapy
• long course radiotherapy
• short-course radiotherapy

Trial Overview The RAPIDO Trial is testing a new treatment approach against standard care in rectal cancer. Patients will either receive short-course radiotherapy followed by chemotherapy before surgery (M1 scheme) or the usual long course chemoradiotherapy before surgery. The goal is to improve survival rates by treating both local tumors and potential micro-metastases early.

How Is the Trial Designed?

Group I: B: 5x5Gy -> CAPOX -> surgery Experimental Treatment 1 Intervention

experimental group (arm B) M1 scheme

Group II: A: 5 weeks chemoradiation -> surgery Active Control 1 Intervention

control group (arm A) standard long course chemoradiotherapy

Who Is Running the Clinical Trial?

University Medical Center Groningen

Lead Sponsor

Trials

770

Recruited

1,101,000+

Leiden University Medical Center

Collaborator

Trials

580

Recruited

623,000+

Karolinska University Hospital

Collaborator

Trials

509

Recruited

1,319,000+

Dutch Cancer Society

Collaborator

Trials

118

Recruited

77,500+

Uppsala University Hospital

Collaborator

Trials

188

Recruited

749,000+

Published Research Related to This Trial

In a study of 155 patients with locally advanced rectal cancer, preoperative short-course radiotherapy followed by surgery showed a low complete pathological response rate of only 2.2%, but 28% of patients experienced downstaging, indicating some effectiveness in tumor size reduction.

The research suggests that waiting more than 20 days after radiotherapy before surgery may improve the chances of achieving a free circumferential resection margin, particularly in patients with mesorectal fascia involvement, which is crucial for reducing the risk of cancer recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Response to treatment and interval to surgery after preoperative short-course radiotherapy in rectal cancer. García-Cabezas, S., Rodríguez-Liñán, M., Otero-Romero, AM., et al.[2017]

In a study of 210 rectal cancer patients treated with preoperative short-course radiotherapy followed by surgery, the 5-year overall survival rate was 66.4%, indicating effective long-term outcomes.

The treatment resulted in excellent local control with a locoregional relapse-free survival rate of 91.7%, and the associated treatment-induced toxicity was low, with severe side effects occurring in only 1% of patients early and 7.6% late.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative short-course radiotherapy in rectal cancer patients: results and prognostic factors. Skóra, T., Nowak-Sadzikowska, J., Martynów, D., et al.[2022]

In a study of 177 patients with resectable rectal cancer, short-course preoperative radiotherapy (25 Gy in five fractions) was linked to a 38% complication rate within 3 months, highlighting the need to identify patients who may not benefit from this treatment.

Factors such as an overall treatment time (OTT) exceeding 13 days, older age, and longer radiotherapy fields were associated with a higher risk of postoperative complications, suggesting that optimizing treatment protocols could reduce acute toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective study of acute toxicity following short-course preoperative radiotherapy. Hartley, A., Giridharan, S., Gray, L., et al.[2004]

In a study comparing short-course radiotherapy followed by chemotherapy to conventional chemoradiotherapy in locally advanced rectal cancer, the pathological complete response (pCR) rate was similar between the two groups, with 6.7% in the study arm and 0% in the control arm, indicating comparable efficacy.

The short-course radiotherapy regimen significantly reduced acute toxicities (14.2% vs. 61.5% in the control arm) while maintaining similar rates of R0 resection (92.8% vs. 92.3%), suggesting better patient compliance and safety with the new treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Prospective Observational Study Comparing Long-Course Conventional Neoadjuvant Chemoradiotherapy with Short-Course Radiotherapy Followed by Consolidation Chemotherapy with Delayed Surgery in Locally Advanced Rectal Cancer. Thakur, N., Seam, RK., Gupta, MK., et al.[2020]

Citations

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

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

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0305737219301252

Should we favour the use of 5 × 5 preoperative radiation in ... SCPRT reduced 5-year local recurrence (LR) rate from 27% to 11% in the Swedish [1] from 11% to 5% in the Dutch TME [2], [5], [6] and from 12% to 5% in the ...

3. esmogastro.org esmogastro.org/article/S2949-8198(24)00028-1/fulltext

Efficacy and safety of short-course radiotherapy versus total ... Efficacy and safety of short-course radiotherapy versus total neoadjuvant therapy in older rectal cancer patients: a randomised pragmatic trial (SHAPERS)

4. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-024-12254-1

The efficacy and safety of short-course radiotherapy followed ... The primary endpoint was the CR rate, which was the ratio of the pathological CR rate plus the clinical CR rate. The secondary endpoints ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2012.42.9597

Randomized Trial of Short-Course Radiotherapy Versus ... The Swedish Rectal Cancer Trial demonstrated that short-course preoperative radiotherapy reduced the risk of local recurrence (LR) by half. In ...

6. 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% ...

7. thegreenjournal.com thegreenjournal.com/article/S0167-8140(25)05198-9/fulltext

A multicenter analysis of early outcomes and toxicity Short-course radiotherapy versus long-course chemoradiotherapy in total neoadjuvant therapy of rectal cancer – A multicenter analysis of early outcomes and ...

8. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(25)00286-4/fulltext?rss=yes

Total neoadjuvant treatment with short-course radiotherapy ... Robotic versus laparoscopic surgery for middle and low rectal cancer (REAL): short-term outcomes of a multicentre randomised controlled trial.

9. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.4_suppl.150

Short-course radiotherapy-based total neoadjuvant therapy ... 150. Background: It has been found that radiotherapy possess synergistic anticancer effect with immune checkpoint inhibitors (ICIs).