Clinical trial NCT02860234: Tailored Operative or Non-operative Management for Low-risk Rectal Cancer After Intensive Neoadjuvant Treatment
Official title: Tailored Operative or Non-operative Management for MRI Defined Low-risk Rectal Cancer Following Neoadjuvant Intensity Modulated Radiotherapy With Concurrent Capecitabine Plus Consolidation CapeOX.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Rectal Cancer
Keywords: Rectal cancer
neoadjuvant
radiotherapy
chemotherapy
organ preservation
Lead sponsor: Peking University Cancer Hospital & Institute
Sponsor class: OTHER
First posted: 2016-08-09
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Rectal cancer patient who receives primary care in Beijing Cancer Hospital will be selected as the candidate for this study.

Brief summary: This study is designed to test the efficacy of tailored operative or non-operative management (NOM) for MRI defined low-risk rectal cancer following neoadjuvant intensity modulated radiotherapy with concurrent capecitabine plus consolidation CapeOX. The main purpose of this study is to increase organ-preservation rate for low-risk rectal cancer patients.

Detailed description: Neoadjuvant chemoradiotherapy (nCRT), total mesorectal excision and adjuvant chemotherapy comprise the standard treatment for locally advanced rectal cancer, following which 15-30% patients achieved pathological complete response need to receive the removal of rectum without residual tumor and suffer significant functional impairment even after sphincter preservation. Adjuvant chemotherapy is also questioned for its benefit for prolonged survival through the data from various studies. More evidence demonstrated that organ-preservation (e.g. non-operative management or local excision) for patients with clinical complete response (cCR) or near-cCR following nCRT had similar survival when compared with those received standard care.

This study is designed to investigate the efficacy of neoadjuvant intensity modulated nCRT with concurrent capecitabine plus consolidation CapeOX for T2/DWI/Enhanced MRI defined cT2-T3b mid-low rectal cancer without threatening mesorectal fascia or extramural vascular invasion (EMVI) or mrN2 disease.

According to the response to treatment evaluated by multi-modal assessment including digital exam, T2/DWI/Enhanced MRI, endoscopy and serum CEA test, patients will receive tailored operative management like local excision or total mesorectal excision, or non-operative management. Intention to treatment was also allowed in this study.

Firstly, the investigators will observe the organ preservation rate at 2 years. Endpoints for organ-preservation like non-regrowth DFS, stoma-free survival and other conventional survival outcomes (DFS, OS) would be further collected. The short-term and long-term QoL will be measured in all patients.

. Our baseline data showed the 48% of locally advanced rectal cancers could be downstaged to stage ypT0-2N0 following IMRT with concurrent capecitabine. We hypothesize that at least 24% of rectal cancers could be candidates for LE or NOM after IMRT and the rectum preservation rate will increase to 40% in low-risk rectal cancers by LE or NOM following IMRT plus consolidation CapeOX at 2 years. As a superiority design, this study need to recruit 64 patients to test this hypothesis, with 85% power (exact binomial test for proportions, alpha = 5 %, one-sided), If the number of responses is 22 or more, the hypothesis that P \<= 0.240 is rejected. We anticipate about 10 % loss to follow-up, so we will recruit an additional 8 patients and the study will recruit 72 patients in all.

Eligibility criteria: Inclusion Criteria:

* Age ≥18 years and ≤85 years
* ECOG Performance status 0-1
* Histologically confirmed diagnosis of adenocarcinoma of the rectum, with tumor differentiation Grade 1-3
* The distance from down verge of tumor to anal-rectal junction (ARJ) ≤8cm based on MRI, or ≤12cm based on sigmoidoscopy;
* Clinical Stage T2 or T3a or T3b and EMVI (-) and MRF (-) and extra-mesorectal metastatic lymph node (-) based on MRI
* No evidence of distant metastases
* No prior pelvic radiation therapy
* No prior chemotherapy or surgery for rectal cancer
* No active infections requiring systemic antibiotic treatment
* ANC \> 1.5 cells/mm3, HGB \> 10.0 g/dL, PLT \> 100,000/mm3, total bilirubin ≤ 1.5 x ULN, AST≤ 3 x ULN, ALT ≤ 3 x ULN.
* Patients must read, agree to, and sign a statement of Informed Consent prior to participation in this study.

Exclusion Criteria:

* Recurrent rectal cancer
* Primary unresectable rectal cancer. A tumor is considered unresectable when invading adjacent organs and an en-bloc resection will not achieve negative margins.
* Creatinine level greater than 1.5 times the upper limit of normal.
* Patients who have received prior pelvic radiotherapy.
* Patients who are unable to undergo an MRI.
* Patients with a history of a prior malignancy within the past 5 years, except for well treated basal cell cancer, squamous cell skin cancer, breast cancer, thyroid cancer or small renal cancer, and with DFS \>5 years.
* Patients with a history of any arterial thrombotic event within the past 6 months. This includes angina (stable or unstable), MI, TIA, or CVA.
* Other Anticancer or Experimental Therapy.
* Women who are pregnant or breast-feeding.
* Patients with any other concurrent medical or psychiatric condition or disease which would make them inappropriate candidates for entry into this study.

Primary outcomes:
measure: Organ preservation rate
timeFrame: 3 years
Secondary outcomes:
measure: Rate of non-regrowth disease-free survival (NR-DFS)
timeFrame: 3 years
measure: Stoma-free survival
timeFrame: 3 years
measure: Major adverse events
timeFrame: 3 years
measure: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30)
timeFrame: Time0: before neoadjuvant treatment; Time1: at 4 months after the completion of neoadjuvant radiation; Time2: 12 months after Time1; Time3: 24 months after Time1; Time4: 36 months after Time1
measure: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Colorectal Cancer Module 29 (EORTC QLQ-CR29)
timeFrame: Time0: before neoadjuvant treatment; Time1: at 4 months after the completion of neoadjuvant radiation; Time2: 12 months after Time1; Time3: 24 months after Time1; Time4: 36 months after Time1
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
Study officials:
References: