Clinical trial NCT02864849: Total Neoadjuvant Induction and Consolidation CapeOX Plus IMRT With Capecitabine for MRI Defined High-risk Rectal Cancer
Official title: Total Neoadjuvant Induction and Consolidation CapeOX Plus Neoadjuvant Intensity Modulated Radiotherapy With Concurrent Capecitabine for MRI Defined High-risk Rectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rectal Cancer
Keywords: Rectal cancer
neoadjuvant
radiotherapy
chemotherapy
toxicity
Lead sponsor: Peking University Cancer Hospital & Institute
Sponsor class: OTHER
First posted: 2016-08-12
Enrollment: 81
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is designed to test the efficacy and safety of total neoadjuvant induction and consolidation CapeOX plus neoadjuvant intensity modulated radiotherapy with concurrent capecitabine for MRI defined high-risk rectal cancer.

Detailed description: This phase II trial is studying the efficacy and safety of total neoadjuvant treatment for MRI defined high-risk locally advanced rectal cancer.

MRI imaging features as mrT3c/T3d/T4a/T4b, threatening circumferential resection margin, mrN2 disease or extramural vascular invasion are defined as high-risk factor and proved to associated with unfavorable oncological outcome, especially for distant metastasis. Induction and consolidation chemotherapy plus radiation may increase both systemic and local control. Total neoadjuvant treatment schedule also has advantages as improved patient tolerance, early closure of defunctioning ileostomy etc.

In this study, patients with MRI defined high-risk rectal cancer will receive 3 cycles induction CapeOX, intensity modulated radiotherapy with concurrent capecitabine and 2 cycles consolidation CapeOX and Total mesorectal excision.

The induction chemotherapy related G3-4 toxicity occurred in 42% of patients in GCR-3 trial (23% during RT, 19% during induction chemotherapy). It is hypothesized that the neoadjuvant chemotherapy related G3-4 toxicity rate of the present regimen will be lower than 25% (10% during IMRT, 15% during induction/consolidation chemotherapy). A sample size of 67 achieves 80% power to detect a difference (△P =17%, P1=25%, P0=42%) using a one-sided binomial test. (α= 0.05). If the number of G3-4 toxic event is 21 or less, the hypothesis that P1\>= 42% is rejected. About 10 % loss to follow-up was anticipated, so an additional eight patients will be recruited. The study requires 75 subjects in all.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years and ≤75 years.
* ECOG Performance status 0-1.
* Histologically confirmed diagnosis of adenocarcinoma of the rectum.
* The distance from down verge of tumor to anal-rectal junction (ARJ) ≤8cm based on MRI, or ≤12 cm based on sigmoidoscopy.
* Clinical Stage T3c, T3d, T4a or T4b, or EMVI (+) or mrN2 or CRM (+) 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.
* Anticipated unresectable tumor after neoadjuvant treatment.
* 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 adequately treated basal cell or squamous cell skin cancer.
* 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: Major adverse events
timeFrame: 3 years
Secondary outcomes:
measure: Disease-free survival (DFS)
timeFrame: 3 years
measure: Pathological downstaging rate
timeFrame: 1 year
measure: Compliance rate with neoadjuvant treatment schedule
timeFrame: 1 year
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: