Pre-operative Chemotherapy for Rectal Cancer

(RAPIDO Trial)

Recruiting at 55 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

920 Participants Needed

Trial Summary

What is the purpose of this trial?

Currently the 3-year disease free survival of patients with locally advanced rectal cancer is about 50%. Current standard treatment for patients at high risk of failing locally and/or systemically includes pre-operative long course radiotherapy (5 weeks) in combination with chemotherapy (so called neoadjuvant chemoradiotherapy). The neoadjuvant chemoradiotherapy has been demonstrated to improve local control, but had no effect on the overall survival. Different studies in patients with rectal cancer studying the effect of adjuvant post operative chemotherapy did not result in an improved survival. This may be due the fact that rectal cancer surgery (TME) is associated with a high complication rate so substantial proportion of patients cannot receive chemotherapy postoperatively. An alternative approach is to administer the systemic therapy preoperative. To guarantee control of the rectum tumor short-course radiotherapy (5 days) is given, as different studies showed local control of the tumor for a long time. During this waiting period the patient is in a good condition to receive an optimal dose of chemotherapy. The investigators hypothesize that with this proposed protocol both the local tumour and possible micrometastases are effectively treated and that this will result in an increased survival. The investigators will compare this with the standard treatment of neoadjuvant chemoradiation followed by TME surgery and optional adjuvant chemotherapy.

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.

What data supports the effectiveness of the treatment for pre-operative chemotherapy and radiotherapy for rectal cancer?

Research shows that both short-course and long-course radiotherapy, when used before surgery, are effective in controlling rectal cancer locally. Short-course radiotherapy is simpler, while long-course chemoradiotherapy can shrink tumors more, potentially preserving the sphincter. Both approaches have shown similar long-term survival and local control, with short-course radiotherapy having fewer acute side effects when combined with chemotherapy. ^{1 2 3 4 5}

Is pre-operative chemotherapy for rectal cancer safe?

Pre-operative chemotherapy and radiotherapy for rectal cancer are generally safe, with low rates of severe side effects. However, some patients may experience complications like stool incontinence or sexual dysfunction, and there is a small risk of more serious side effects. ^{1 6 7 8 9}

How does pre-operative chemotherapy for rectal cancer differ from other treatments?

Pre-operative chemotherapy for rectal cancer often involves either short-course or long-course radiotherapy. Short-course radiotherapy is simpler and involves immediate surgery, while long-course chemoradiotherapy can shrink tumors more effectively, potentially preserving the sphincter. The choice between these approaches depends on the specific clinical situation and remains a topic of ongoing research. ^{1 2 4 10 11}

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

Eligibility Criteria

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

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

I have a known DPD deficiency.

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

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

References

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

Preoperative Treatment of Locally Advanced Rectal Cancer: Assets and Drawbacks of Short Course and Long Course in Clinical Practice. [2018]

2. Spain pubmed.ncbi.nlm.nih.gov

Response to treatment and interval to surgery after preoperative short-course radiotherapy in rectal cancer. [2017]

3. India 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. [2020]

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

Timing of surgery after long-course neoadjuvant chemoradiotherapy for rectal cancer: a systematic review of the literature. [2021]

5. Germany pubmed.ncbi.nlm.nih.gov

Preoperative short-course radiotherapy in rectal cancer patients: results and prognostic factors. [2022]

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

Downstaging in Advanced Rectal Cancers: A Propensity-Matched Comparison Between Short-Course Radiotherapy Followed by Chemotherapy and Long-Course Chemoradiotherapy. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Retrospective study of acute toxicity following short-course preoperative radiotherapy. [2004]

8. England pubmed.ncbi.nlm.nih.gov

Clinical results and toxicity for short-course preoperative radiotherapy and total mesorectal excision in rectal cancer patients. [2022]

9. England pubmed.ncbi.nlm.nih.gov

A Retrospective Analysis on Two-week Short-course Pre-operative Radiotherapy in Elderly Patients with Resectable Locally Advanced Rectal Cancer. [2022]

10. Czech Republic pubmed.ncbi.nlm.nih.gov

Preoperative radiotherapy of locally advanced rectal cancer: clinical outcome of short-course and long-course treatment with or without concomitant chemotherapy. [2012]

11. France pubmed.ncbi.nlm.nih.gov

[Preoperative radiochemotherapy for rectal cancer: forecasting the next steps through ongoing and forthcoming studies]. [2018]