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

Colorectal Cancer Clinical Trial

— NEOLAR  

Official title:

NEOadjuvant Chemotherapy Only Compared With Standard Treatment for Locally Advanced Rectal Cancer: a Randomized Phase II Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03280407
• Other study ID #: S-20160158
• Status: Recruiting
• Phase: Phase 2
• First received: September 7, 2017
• Last updated: September 26, 2017
• Start date: March 1, 2017
• Est. completion date: December 31, 2024

Study information

• Verified date: September 2017
• Source: Zealand University Hospital
• Contact: Ismail Gögenur, MD
• Phone: +45 26336426
• Email: igo[@]regionsjaelland.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 124
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chemotherapy Effect
• Colorectal Cancer
• Colorectal Neoplasm
• Colorectal Neoplasms
• Intestinal Disease
• Intestinal Diseases
• Intestinal Neoplasms
• Neoplasms
• Rectal Cancer
• Rectal Neoplasms

Intervention

Drug:
• Capecitabine
Radio-chemotherapy with 50.4 Gy in 28 fractions to tumor and regional lymph nodes concomitantly with capecitabine 825 mg/m2 b.i.d
• FOLFOX regimen (oxaliplatin/leucovorin/5FU)
Six cycles: Oxaliplatin 85 mg/m2 day 1, leucovorin 400 mg/m2 day 1, 5FU 400 mg/m2 bolus day 1 and 5FU 2400 mg/ m2 over 46-48 hours day 1-3, repeated every two weeks.
• CAPOX (oxaliplatin/capecitabine)
Four cycles: Oxaliplatin 130 mg/m2 day 1 and capecitabine 1000 mg/m2 b.i.d. days 1-14, repeated every 3 weeks.

Locations

Country	Name	City	State
Denmark	Vejle Hospital	Vejle

Sponsors (1)

Lead Sponsor	Collaborator
Zealand University Hospital

Country where clinical trial is conducted

Denmark, 

Outcome

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