NEOadjuvant Chemotherapy Only Compared With Standard Treatment for Locally Advanced Rectal Cancer

Phase 2

Recruiting

• Conditions: Colorectal Neoplasm; Colorectal Cancer; Rectal Neoplasms; Chemotherapy Effect; Intestinal Disease; Intestinal Neoplasms; Rectal Cancer
• Interventions: Drug: FOLFOX regimen (oxaliplatin/leucovorin/5FU); Drug: Capecitabine; Drug: CAPOX (oxaliplatin/capecitabine)

• Registration Number: NCT03280407
• Lead Sponsor: Zealand University Hospital

Brief Summary

The main clinical hypothesis is that compared to radio-chemotherapy for low and mid rectal tumors or surgery for high rectal tumors neoadjuvant chemotherapy reduces the rate of distant relapse without increasing the rate of local relapse.

The aim of the present study is to compare long term and short term outcomes in rectal cancer patients undergoing standard treatment (radio-chemotherapy/surgery) or experimental neoadjuvant chemotherapy/surgery Furthermore, early surgical and medical complications, the functional outcome, toxicity and quality of life (QoL) may be improved if radiotherapy can be avoided.

Exploratory analyses are planned in order to find potential predictive markers for selecting patients to either radio-chemotherapy/surgery or neoadjuvant combination chemotherapy/surgery.

Detailed Description

The standard treatment of locally advanced but resectable cancer in the middle or lower rectum is preoperative radio-chemotherapy and in the upper part initial surgery. The clinical benefit from radio-chemotherapy is primarily through a reduction in local relapse but the treatment is associated with acute toxicity and long term functional dysfunction. Subsequently, it is important to select patients with high risk of local relapse. Intense systemic combination chemotherapy reduces the risk of distant relapse and increases survival in the postoperative setting. The biological rationale is eradication of micrometastases and hence it may be anticipated that earlier, i.e. neoadjuvant, combination therapy may improve systemic control.

Study Timeline

• Study Start: 2017-03-01
• Status Verified: 2017-09
• Study First Submitted: 2017-09-07
• Study First Submitted QC: 2017-09-08
• Study First Posted: 2017-09-12
• Last Update Submitted: 2017-09-26
• Last Update Posted: 2017-09-28
• Primary Completion: 2018-12-31
• Study Completion: 2024-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 124

Inclusion Criteria

• Adenocarcinoma of the rectum with the lower boarder within 15 cm from the anal verge
• Locally advanced tumor based on imaging
• T3 tumors within 10 cm from the anal verge fulfilling the criteria for preoperative radio-chemotherapy according to Danish Colorectal Cancer Group (DCCG) guidelines
• T3c or T4 tumors 10-15 cm from the anal verge
• Deemed resectable at the multidisciplinary team (MDT) conference
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Age at least 18 years
• Adequate bone marrow, liver and renal function allowing systemic chemotherapy
• Absolute neutrophil count ≥1.5x109/l and thrombocytes ≥ 100x109/l.
• Bilirubin ≤ 1.5 x upper normal value and alanine aminotransferase ≤ 3 x upper normal value
• Calculated or measured renal glomerular filtration rate at least 30 mL/min
• Anticonception for fertile women and for male patients with a fertile partner. Intrauterine device, vasectomy of a female subject's male partner or hormonal contraceptive are acceptable
• Written and orally informed consent

Exclusion Criteria

• Distant metastasis
• Invasive ingrowth into other organs
• Incapacity, frailty, disability and comorbidity to a degree that according to the investigator is not compatible with combination chemotherapy
• Previous radiotherapy to the pelvis
• Previous treatment with 5FU or oxaliplatin
• Surgery within two weeks
• Neuropathy NCI grade > 1
• Other malignant tumor within 5 years except non-melanoma skin cancer or carcinoma in situ cervicis uteri
• Pregnant (positive pregnancy test) or breast feeding women

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
B, FOLFOX or CAPOX	FOLFOX regimen (oxaliplatin/leucovorin/5FU)	Neoadjuvant chemotherapy with CAPOX (oxaliplatin/capecitabine) or FOLFOX regimen (oxaliplatin/leucovorin/5FU), according to institutional practice
B, FOLFOX or CAPOX	CAPOX (oxaliplatin/capecitabine)	Neoadjuvant chemotherapy with CAPOX (oxaliplatin/capecitabine) or FOLFOX regimen (oxaliplatin/leucovorin/5FU), according to institutional practice
A, capecitabine	Capecitabine	Radiochemotherapy with 50.4 Gy in 28 fractions concomitantly with chemotherapy

Primary Outcome Measures

Name	Time	Method
Disease free survival	5 years	All patients will be evaluated with CT and MRI scans and clinically every 6 months for 2 years and annually until the number of events is reached and the trial is stopped (max 5 years)

Secondary Outcome Measures

Name	Time	Method
Early toxicity	5 years	Evaluated using CTCEA (Common Terminology Criteria for Adverse Events) version 4.
Functional outcome	5 years	Measured with LARS questionnaire
Late toxicity	5 years	Evaluated using CTCEA version 4.
Quality of life (QoL)	5 years	Measured with EORTC QoL questionnaire
Local relapse	5 years	Defined to be within the pelvis. Any relapse should be verified by biopsy
Overall survival	5 years	All patients will be evaluated with CT and MRI scans and clinically every 6 months for 2 years and annually for maximum 5 years
Distant relapse	5 years	Defined to be outside the pelvis. Any relapse should be verified by biopsy

Trial Locations

Locations (1)

Vejle Hospital; 🇩🇰 Vejle, Denmark