Neoadjuvant Chemotherapy, Excision And Observation vs Chemoradiotherapy For Rectal Cancer

Rectal Cancer Clinical Trial

— NEO-RT  

Official title:

A Phase 3 Randomized Trial Of Neoadjuvant Chemotherapy, Excision And Observation Versus Chemoradiotherapy For Early Rectal Cancer

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06205485
• Other study ID #: CCTG-CO32
• Secondary ID: CCTG-CO32NCI-202
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: July 31, 2024
• Est. completion date: June 30, 2030

Study information

• Verified date: June 2024
• Source: Canadian Cancer Trials Group
• Contact: Chris O'Callaghan
• Phone: 613-533-6430
• Email: cocallaghan[@]ctg.queensu.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is being done to answer the following questions: Is the chance of rectal cancer responding the same if chemotherapy alone is given before limited surgery compared to chemotherapy and radiation therapy given together before limited surgery? If radiation therapy is not given, is quality of life better?

Description:

This study is being done to find out if this approach is better or worse than the usual approach for early rectal cancer. The usual approach is defined as care most people get for early rectal cancer.

The usual approach for patients who are not in a study is surgery to remove the rectum or treatment with chemotherapy and radiation therapy, followed by surgery. There are several chemotherapy drugs approved by Health Canada that are commonly used with radiation therapy. For patients who get the usual approach for this cancer, about 90 out of 100 are free of cancer after 5 years.

If a patient decides to take part in this study, they will either get a combination of chemotherapy drugs called FOLFOX or CAPOX for up to 12 weeks or will get chemotherapy with radiation therapy for up to 6 weeks.

After finishing treatment, and even if treatment is stopped early, the study doctor will watch for side effects and determine which type of surgery would be best. After surgery, patients will be asked to come in every 4 months for 2 years, then every 6 months for an additional year. Then will be checked every year for 2 years. This means seeing the study doctor for up to 5 years after surgery. Patients may be seen more often if your study doctor thinks it is necessary.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 250
• Est. completion date: June 30, 2030
• Est. primary completion date: January 30, 2030
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically confirmed invasive, well-moderately differentiated rectal adenocarcinoma, mismatch repair proficient.

• MRI stage cT1 not eligible for transanal surgery or cT2.

• cN0 stage based on pelvic MRI - including absence of radiographic evidence of mesorectal nodal metastasis, tumour deposits or extramural venous invasion (EMVI).

• M0 stage based on no evidence of metastatic disease by CT imaging of chest, abdomen and pelvis.

• Mid to low-lying tumour eligible for transanal excision in the opinion of the treating surgeon.

• Medically fit to undergo radical TME surgery as per treating surgeon's decision.

• Participant is able (i.e. sufficiently fluent) and willing to complete the quality of life questionnaires in either English or French or Spanish.

• Age of at least 18 years.

• No contraindications to protocol chemotherapy.

• Adequate normal organ and marrow function: ANC = x 10^9/L; platelet count = 100 x 10^9/L; bilirubin < 1.5 UNL, excluding Gilbert's syndrome; Estimated creatinine clearance of = 50ml/min

• Patient must have an ECOG performance of <2 (or Karnofsty = 60%).

• Must be accessible for treatment and follow-up

• Women/men of childbearing potential must have agreed to use a highly effective contraceptive method during and for 6 months after completion of chemotherapy.

• HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.

Exclusion Criteria:

• Pathologic high-risk factors on diagnostic biopsy: high histologic grade (poorly differentiated), mucinous or signet ring histology, lymphatic/vascular or perineural invasion.

• Patients with visible pelvic sidewall nodes on MRI.

• Patients with unequivocal determination of nodal disease that, in the opinion of the investigator, would prohibit protocol therapy administration.

• Previous pelvic radiation for any reason, including brachytherapy alone.

• Patients who have had primary lesion excised prior to enrollment.

• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.

• Prior treatment for rectal cancer.

• Patients with known dihydropyrimidine dehydrogenase deficiency (DYPD).

• Potential trial participants should have recovered from clinically significant adverse events of their most recent therapy/intervention prior to enrollment.

• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better.

• Any contra-indications to undergo MRI imaging.

• Presence of anterior lesions above or near peritoneal reflection rendering the patient ineligible for a transanal tumour excision.

Related Conditions & MeSH terms

• Rectal Cancer
• Rectal Neoplasms

Intervention

Drug:
• Leucovorin
400 mg/m2
• Oxaliplatin
85 mg/m2 or 130 mg/m2 on day 1
• Fluoruracil
bolus fluoruracil (optional) 400 mg, infusional fluorouracil 2,400 mg/m2
• Capecitabine
1,000 mg/m2 twice daily for 14 days

Radiation:
• Radiation
54 Gy (27-30 fractions)

Locations

Country	Name	City	State
United States	Miami Valley Hospital South	Centerville	Ohio
United States	Northwestern University	Chicago	Illinois
United States	Carle at The Riverfront	Danville	Illinois
United States	Miami Valley Hospital	Dayton	Ohio
United States	Miami Valley Hospital North	Dayton	Ohio
United States	Premier Blood and Cancer Center	Dayton	Ohio
United States	Carle Physician Group-Effingham	Effingham	Illinois
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	Miami Valley Cancer Care and Infusion	Greenville	Ohio
United States	Legacy Mount Hood Medical Center	Gresham	Oregon
United States	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois
United States	Providence Newberg Medical Center	Newberg	Oregon
United States	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California
United States	Providence Willamette Falls Medical Center	Oregon City	Oregon
United States	Legacy Good Samaritan Hospital and Medical Center	Portland	Oregon
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Upper Valley Medical Center	Troy	Ohio
United States	Legacy Meridian Park Hospital	Tualatin	Oregon
United States	Carle Cancer Center	Urbana	Illinois
United States	Legacy Cancer Institute Medical Oncology and Day Treatment	Vancouver	Washington
United States	Legacy Salmon Creek Hospital	Vancouver	Washington

Sponsors (5)

Lead Sponsor	Collaborator
Canadian Cancer Trials Group	Alliance for Clinical Trials in Oncology, ECOG-ACRIN Cancer Research Group, NRG Oncology, SWOG Cancer Research Network

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical response rate upon re-staging		6 years
Primary	Quality of Life defined using the LARS score		6 years
Secondary	Total Mesorectal Excision (TME) Free Survival	Defined as time from randomization to the time of TME attempt or performance, local recurrence after complete clinical response (cCR), or death from any cause	6 years
Secondary	Disease Free Survival	Defined as time from randomization to local recurrence/regrowth after cCR that cannot be salvaged with an R0 TM, M1 recurrence, or death	6 years
Secondary	Rate of downstaging to ypTO/1N0/X		6 years
Secondary	Bowel function assessed by Low Anterior Resection Syndrome (LARS) Score		6 years
Secondary	Bladder function assessed by EORTC QLQ-CR29 urinary frequency and urinary incontinence subscales		6 years
Secondary	Sexual function assessed by EORTC QLQ-CR29 sexual interest (men), and sexual interest (women) subscales		6 years
Secondary	Other QoL functions assessed by subscales of FIQL		6 years
Secondary	Other QoL functions assessed by subscales of EORTC QLQ-C30		6 years
Secondary	Other QoL functions assessed by subscales of subscales of EORTC QLQ-CR29		6 years
Secondary	Number and severity of adverse events utilizing CTCAE v5.0		6 years
Secondary	Validate the magnetic resonance tumour regression grade (MR-TRG) in patients with T1 and T2 rectal cancer		6 years