A Prospective Phase II Randomized Clinical Trial of Preoperative Chemotherapy Combined With Short-course Radiotherapy Versus Conventional Neo-adjuvant Therapy for Locally Advanced Rectal Cancer Implemented by MDT

The study is designed to analyze the pathological tumor response on locally advanced rectal cancer after preoperative treatment with neo-adjuvant therapy regimen or with chemotherapy combined with short-course radiotherapy in a prospective cohort and to correlate this response with patient's outcome

Study Overview

• Status: Unknown
• Conditions: Rectal Cancer, Radiotherapy
• Intervention / Treatment: Radiation: Short-course radiotherapy; Drug: FOLFOX4 chemotherapy,preoperative; Procedure: Radical rectal cancer resection; Drug: FOLFOX4 chemotherapy,post-operative; Radiation: Radiotherapy of neo-adjuvant therapy; Drug: Concurrent chemotherapy of neo-adjuvant therapy

Detailed Description

This is a phase II , open label, randomized study in patients with confirmed diagnosis of locally advanced rectal cancer. The study is designed to analyze the pathological tumor response on locally advanced rectal cancer after preoperative treatment with neo-adjuvant therapy regimen or with chemotherapy combined with short-course radiotherapy.

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Phase 2

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 1. Consent to this study
• 2. Histological or cytological confirmed diagnostic of rectal carcinoma
• 3. Locally advanced rectal cancer without metastasis, confirmed by pelvic MRI (cT3CRM+、cT4NX or cTxN2M0)(cT3CRM+: margin between the deepest point of tumor and rectal adventitia/serosa surface is less than 1 mm measured in pelvic MRI)
• 4.With no presence of anemia (Hb≤60g/l) induced by tumor bleeding or bowel obstruction
• 5.With no presence of other organ metastasis or extra-regional lymph node involvement
• 6.With no history of chemotherapy
• 7.ECOG score is 0 or 1
• 8.Adequate ability of bone marrow, liver and kidney function
• 9.No pregnancy

Exclusion Criteria:

1. Unable to intake oral medicine
2. Arrhythmia need treatment(besides β-blocker or digoxin); Symptomatic coronary artery disease or history of myocardiac infarction within 6 months ；Congestive Heart Failure NYHA II grade or severe
3. HIV infection or Active chronic HBV or HCV
4. Severe clinical infection at active stage
5. Epileptic seizure need treatment
6. History of organ transplantation
7. Renal failure or intaking renal dialysis
8. Clinical hemorrhagic tendency or Disorders of blood coagulation or intaking anticoagulant or thrombolytics
9. Severe unhealed wound or skin ulcer or bone fraction
10. Measurable massive ascites 11 History of other malignant tumor(except cured cervical tumor in site and cured cutaneous basal cell carcinoma) in last 5 years

12.Chronic inflammatory bowel disease， bowel obstruction，hereditary fructose intolerance 13.Medicine abuse；medical，psychologic or social conditions might disturb patients or results 14.Known or suspected allergy to any drugs in this study 15.Any situation or status that might endanger patient's safety or compliance 16.Pregnant woman or suckling period woman; Fertility without taking sufficient contraception 17.History of pelvic radiotherapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Preoperative chemotherapy with short-course radiotherapy; Preoperative treatment:4 course of FOLFOX4 therapy combined with short-course radiotherapy	Radiation: Short-course radiotherapy; Preoperative Radiation doses: 25 Gy in 5 fractions to the pelvis; Drug: FOLFOX4 chemotherapy,preoperative; FOLFOX4 chemotherapy：5-FU 400 mg/m2 i.v. bolus and Leucovorin 200 mg/m2 i.v. followed by 5-FU 600 mg/m2 i.v. 22 h-infusion day 1 + 2, oxaliplatin 85 mg/m2 day 1. Repeat every 2 weeks; Procedure: Radical rectal cancer resection; Radical rectal cancer resection; Drug: FOLFOX4 chemotherapy,post-operative; FOLFOX4 chemotherapy：5-FU 400 mg/m2 i.v. bolus and Leucovorin 200 mg/m2 i.v. followed by 5-FU 600 mg/m2 i.v. 22 h-infusion day 1 + 2, oxaliplatin 85 mg/m2 day 1. Repeat every 2 weeks
ACTIVE_COMPARATOR: Preoperative neo-adjuvant therapy; Preoperative treatment:neo-adjuvant therapy	Procedure: Radical rectal cancer resection; Radical rectal cancer resection; Drug: FOLFOX4 chemotherapy,post-operative; FOLFOX4 chemotherapy：5-FU 400 mg/m2 i.v. bolus and Leucovorin 200 mg/m2 i.v. followed by 5-FU 600 mg/m2 i.v. 22 h-infusion day 1 + 2, oxaliplatin 85 mg/m2 day 1. Repeat every 2 weeks; Radiation: Radiotherapy of neo-adjuvant therapy; Preoperative Radiation doses: 45 Gy in 25 fractions to the pelvis, 5.4 Gy in 3 fractions to the pelvis; Drug: Concurrent chemotherapy of neo-adjuvant therapy; Capecitabine 825mg/m2 twice daily 5 days/week

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological Response	Treatment effects of interventions. The tumor response should be graded on a scale of 0 (complete response- no viable cancer cells observed) to 3 (poor response - minimal or no tumor kill; extensive residual cancer)	Surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3-year Disease-Free Survival	time from radical resection to recurrence or end of follow-up	3 years
3-year Overall Survival	time from radical resection to cancer caused death or end of follow-up	3 year

Collaborators and Investigators

• Sponsor: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Study record dates

Study Major Dates

• Study Start: December 1, 2016
• Primary Completion (ANTICIPATED): December 1, 2019

Study Registration Dates

• First Submitted: October 20, 2016
• First Submitted That Met QC Criteria: October 20, 2016
• First Posted (ESTIMATE): October 21, 2016

Study Record Updates

• Last Update Posted (ESTIMATE): October 24, 2016
• Last Update Submitted That Met QC Criteria: October 21, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: rectal cancer, radiotherapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Micronutrients; Vitamins; Antidotes; Vitamin B Complex; Fluorouracil; Oxaliplatin; Leucovorin
• Other Study ID Numbers: XHGC-004