Clinical trial NCT03280407: NEOadjuvant Chemotherapy Only Compared With Standard Treatment for Locally Advanced Rectal Cancer
Official title: NEOadjuvant Chemotherapy Only Compared With Standard Treatment for Locally Advanced Rectal Cancer: a Randomized Phase II Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Colorectal Neoplasm
Colorectal Cancer
Rectal Neoplasms
Chemotherapy Effect
Intestinal Disease
Intestinal Neoplasms
Rectal Cancer
Keywords: Neoadjuvant chemotherapy,
locally advanced rectal cancer,
chemotherapy
CAPOX (oxaliplatin/capecitabine)
FOLFOX (oxaliplatin/leucovorin/5FU)
Lead sponsor: Zealand University Hospital
Sponsor class: OTHER
First posted: 2017-09-12
Enrollment: 124
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is an open label, randomized phase II screening trial allocating eligible patients to either standard treatment for rectal cancer or experimental preoperative combination chemotherapy.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Disease free survival
timeFrame: 5 years
Secondary outcomes:
measure: Overall survival
timeFrame: 5 years
measure: Local relapse
timeFrame: 5 years
measure: Distant relapse
timeFrame: 5 years
measure: Early toxicity
timeFrame: 5 years
measure: Late toxicity
timeFrame: 5 years
measure: Functional outcome
timeFrame: 5 years
measure: Quality of life (QoL)
timeFrame: 5 years
Other outcomes:
Locations:
city: Vejle
country: Denmark
facility: Vejle Hospital
Study officials:
affiliation: Department of Surgery, ZUH
name: Ismail Gögenur, MD
role: STUDY_CHAIR
affiliation: Vejle Hospital
name: Lars Henrik Jensen, MD
role: PRINCIPAL_INVESTIGATOR
References: