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

Rectal Neoplasms Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03484221
• Other study ID #: LGIOG-2017-02
• Status: Recruiting
• Phase: Phase 2
• Start date: April 1, 2018
• Est. completion date: April 1, 2022

Study information

• Verified date: April 2021
• Source: China Medical University, China
• Contact: Yuanhe Wang, PhD
• Phone: 18900918794
• Email: zhangjd0228[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: April 1, 2022
• Est. primary completion date: October 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Drug Therapy
• Radiation
• Rectal Neoplasms

Intervention

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).

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.

Locations

Country	Name	City	State
China	China Medical University	Shenyang

Sponsors (1)

Lead Sponsor	Collaborator
China Medical University, China

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Tumor regression grade (TRG)	The level of tumor regression under pathological examination	2 years
Secondary	Disease free survival	Estimated from the date of surgery to the date of recurrence.	3 years
Secondary	Overall survival time	Estimated from the date of enrollment to death from any cause.	3 years
Secondary	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
Secondary	ctDNA change	The relationship between ctDNA and survival will be evaluated.	3 years
Secondary	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)
Secondary	Quality of life (QLQ C30)	Scores according to EORTC QLQ-C30 scoring manual	Every 2 weeks after the first treatment until 3 years