Totally Neoadjuvant FOLFOXIRI + Short-course Radiation + XELOX in Patients With Locally Advanced Rectal Cancer

Totally Neoadjuvant FOLFOXIRI Chemotherapy Followed by Short-course Radiation and XELOX Chemotherapy in Patients With Locally Advanced Rectal Cancer：an Open-label, Single-arm, Multicenter Phase II Study.

To evaluate the efficacy and safety of totally neoadjuvant FOLFOXIRI chemotherapy (irinotecan, oxaliplatin and fluorouracil) followed by short-course radiation therapy and XELOX chemotherapy in the patients with locally advanced rectal cancer.

Study Overview

• Status: Recruiting
• Conditions: Rectal Neoplasms; Drug Therapy; Radiation
• Intervention / Treatment: Drug: FOLFOXIRI; Radiation: Short-Course Radiation Therapy(5Gy*5); Drug: XELOX

Detailed Description

Neoadjuvant chemoradiation therapy with double cytotoxic agents is the standard treatment for the patients with locally advanced rectal cancer. Conventional treatment reduced the local recurrence but did not prolong the long-term survival. Furthermore, the patients with pathological complete response (pCR) did not benefit from double cytotoxic chemotherapy. Therefore, we chose triple cytotoxic agents FOLFOXIRI as the neoadjuvant chemotherapy. We will evaluate the efficacy and safety of totally neoadjuvant FOLFOXIRI chemotherapy (irinotecan, oxaliplatin and fluorouracil) followed by short-course radiation and XELOX chemotherapy in the patients with locally advanced rectal cancer to achieve more pCR and longer survival.

In this prospective study, 30 patients with locally advanced rectal cancer will be recruited. Firstly, 4 cycles of neoadjuvant FOLFOXIRI chemotherapy were administered. Subsequently, a short-course radiation therapy (5Gy*5) will be performed. After that, 4 cycles of XELOX chemotherapy will be administered followed by TME surgery. PET-CT examination will be performed before and after the 4 cycles of neoadjuvant FOLFOXIRI chemotherapy to assess the SUVmax changes. In addition, the dynamic changes of ctDNA in peripheral blood will be monitored at the PET-CT examination. In the course of treatment, safety evaluation will be carried out according to the standard of adverse reaction classification (CTCAE) 4.0.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yuanhe Wang, PhD; Phone Number: 18900918794; Email: zhangjd0228@hotmail.com

Study Locations

• China
  • Shenyang, China
    • Recruiting
    • China Medical University
    • Contact: Yuanhe Wang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age: 18-75 years old
• Primary and pathological diagnosis of rectal adenocarcinoma
• Radiographic evaluation of initial resectable rectal cancer
• T staging was determined by MRI as T3N+ or T4Nx
• Distal border of the tumor must be located < 12 cm from the anal verge
• ECOG status: 0～1
• Adequate bone marrow, hepatic and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment:

Neutrophil count≥1.5×10^9/L Platelet count≥90×10^9/L Hemoglobin≥90g/L Total bilirubin (TBI) ≤ 1.5 * ULN Alanine aminotransferase (ALT)≤2.5 * ULN Aspartate aminotransferase (AST)≤2.5 * ULN Alkaline phosphatase (ALP)≤2.5 * ULN

- Signed informed consent; able to comply with study and/or follow- up procedures

Exclusion Criteria:

• Previous treatment with oxaliplatin, irinotecan or fluorouracil
• Hypersensitivity to fluorouracil, oxaliplatin or irinotecan.
• Clear indication of involvement of the pelvic side walls by imaging
• With distant metastasis
• A history of malignant rectal cancer (i. e. sarcoma, lymphoma, carcinoid, squamous cell carcinoma) or synchronous colon cancer
• Cardiovascular disease that would preclude study treatment or follow-up; New York Heart Association class III or IV heart disease; active ischemic heart disease; myocardial infarction within the past 6 months; symptomatic arrhythmia uncontrolled hypertension. Unexplained syncope occurred within 3 months
• Digestive system diseases that would preclude study treatment or follow-up within the past 6 months
• Gastric ulcers or duodenal ulcers for the treatment of resistance;
• 3 or 4 grade gastrointestinal bleeding / bleeding;
• Gastrointestinal perforation / fistula;
• Abdominal abscess;
• Infectious or inflammatory bowel disease
• HIV infection and/or active hepatitis B virus infection
• Pregnant or lactating women. Fertile patients must use effective contraception
• Any serious acute or chronic disease that can not be involved in the study or to influence the interpretation of the results of the study
• Other intervention clinical trials were combined at the same time.
• Nerve or mental abnormality affecting cognitive ability
• Other malignancy except effectively treated squamous cell or basal cell skin cancer,
• Other situations that the researchers think should be excluded

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: FOLFOXIRI+short-course radiation+XELOX; Firstly, 4 cycles of neoadjuvant FOLFOXIRI chemotherapy were administered. Subsequently, a short-course radiation therapy (5Gy*5) will be performed. After that, 4 cycles of XELOX chemotherapy will be administered followed by surgery.

Drug: FOLFOXIRI; IRINOTECAN 150 mg/m^2 IV over 1-h, day 1 + OXALIPLATIN 85 mg/m^2 IV over 2-h, day 1 + L-LEUCOVORIN 200 mg/m^2 IV over 2-h, day 1 + 5-FLUOROURACIL 2800 mg/m^2 IV 48-h continuous infusion, starting on day 1 administered every two weeks for 4 cycles (2 months).; Other Names: Irinotecan; 5-Fluorouracil; Oxaliplatin; Radiation: Short-Course Radiation Therapy(5Gy*5); Patients received a short-course radiation therapy(5Gy*5) after 4 cycles of FOLFOXIRI.; Drug: XELOX; OXALIPLATIN 130 mg/m^2 IV over 2-h, day 1 Capecitabine 1000 mg/m^2 twice daily days 1-14 every 3 weeks for 4 cycles.; Other Names: Capecitabine; Oxaliplatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The ratio of tumor downstaging to stage 0 and stage I	Tumor downstaging from stage II or III to pathologic complete response (stage 0) and stage I	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor regression grade (TRG)	The level of tumor regression under pathological examination	2 years
Disease free survival	Estimated from the date of surgery to the date of recurrence.	3 years
Overall survival time	Estimated from the date of enrollment to death from any cause.	3 years
Quality of life (QLQ C30)	Scores according to EORTC QLQ-C30 scoring manual	Every 2 weeks after the first treatment until 3 years
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	The grade of toxicity will be assessed using the NCI-CTCAE version 4.0.	3 years
ctDNA change	The relationship between ctDNA and survival will be evaluated.	3 years
SUVmax changes	Tumor metabolic response through FDG-PET examination before and after 4 cycles of neoadjuvant FOLFOXIRI chemotherapy	At the beginning of Cycle 1 and the end of Cycle 4 (each cycle is 14 days)

Collaborators and Investigators

• Sponsor: China Medical University, China

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2018
• Primary Completion (Anticipated): October 1, 2021
• Study Completion (Anticipated): April 1, 2022

Study Registration Dates

• First Submitted: March 23, 2018
• First Submitted That Met QC Criteria: March 29, 2018
• First Posted (Actual): March 30, 2018

Study Record Updates

• Last Update Posted (Actual): April 14, 2021
• Last Update Submitted That Met QC Criteria: April 13, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• 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; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Fluorouracil; Capecitabine; Oxaliplatin; Irinotecan
• Other Study ID Numbers: LGIOG-2017-02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No