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

NCT ID: NCT03484221

Last Updated: 2021-04-14

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-04-01
• Study Completion Date: 2022-04-01

Brief Summary

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.

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.

Conditions

Rectal Neoplasms; Drug Therapy; Radiation

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

FOLFOXIRI

Intervention Type: DRUG

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).

Short-Course Radiation Therapy(5Gy*5)

Intervention Type: RADIATION

Patients received a short-course radiation therapy(5Gy\*5) after 4 cycles of FOLFOXIRI.

XELOX

Intervention Type: DRUG

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.

Interventions

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).

Intervention Type: DRUG

Short-Course Radiation Therapy(5Gy*5)

Patients received a short-course radiation therapy(5Gy\*5) after 4 cycles of FOLFOXIRI.

Intervention Type: RADIATION

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.

Intervention Type: DRUG

Other Intervention Names

Irinotecan; Oxaliplatin; 5-Fluorouracil; Capecitabine; Oxaliplatin

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

China Medical University, China

OTHER

Sponsor Role: lead

Responsible Party

Jingdong Zhang

Director

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jingdong Zhang

Role: PRINCIPAL_INVESTIGATOR

China Medical University, China

Locations

China Medical University

Shenyang, , China

Site Status: RECRUITING

Countries

China

Central Contacts

Yuanhe Wang, PhD

Role: CONTACT

zhangjd0228@hotmail.com

18900918794

Facility Contacts

Yuanhe Wang

Role: primary

Other Identifiers

LGIOG-2017-02

Identifier Type: -

Identifier Source: org_study_id