Open-label Phase II Study of Induction Treatment With Folfoxiri Plus Bevacizumab Followed by Preoperative Chemoradiotherapy Plus Bevacizumab in Patients With Locally Advanced, Resectable Rectal Cancer.

Azienda Ospedaliero, Universitaria Pisana4 sites in 1 country49 target enrollmentMarch 2012

ConditionsRectal Cancer

InterventionsFOLFOXIRI plus Bevacizumab Chemoradiotherapy plus Bevacizumab

DrugsFOLFOXIRI plus Bevacizumab

Overview

Phase: Phase 2
Intervention: FOLFOXIRI plus Bevacizumab
Conditions: Rectal Cancer
Sponsor: Azienda Ospedaliero, Universitaria Pisana
Enrollment: 49
Locations: 4
Primary Endpoint: Disease-free survival rate at 2 years
Status: Completed
Last Updated: 8 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This study includes patients affected by advanced and resectable rectal adenocarcinoma. It provides an induction chemotherapy with FOLFOXIRI regimen plus Bevacizumab followed by Chemoradiotherapy plus Bevacizumab. Surgery with total mesorectal incision must be performed within 7-9 weeks after this last treatment. The protocol will be evaluate the disease free survival at two years. Translational analyses will be performed to show the presence of VEGF polymorphism, CD133 surface markers on colorectal CSCs.

Registry

clinicaltrials.gov

Start Date

March 2012

End Date

March 12, 2018

Last Updated

8 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Azienda Ospedaliero, Universitaria Pisana

Responsible Party

Principal Investigator

Alfredo Falcone

Prof.

Azienda Ospedaliero, Universitaria Pisana

Eligibility Criteria

Inclusion Criteria

•Histologically proven diagnosis of rectal adenocarcinoma. Diagnosis obtained by a biopsy technique which leaves the major portion of the tumor intact.
•Locally advanced, resectable disease defined by the presence of at least one of the following features: tumour extending to within 1 mm of or beyond the mesorectal fascia (ie, circumferential radial margin threatened or involved); lower third (≤ 6 cm from the anal verge) cT3 tumours; tumour extending 5 mm or more into perirectal fat; T4 tumour (ie, invading surrounding structures or peritoneum); clinical stage III disease (T1-4, N1-2), with the definition of a clinically positive lymph node being any node ≥ 1.0 cm;
•Distal border of the tumor must be located \< 12 cm from the anal verge.
•No evidence of metastatic disease by CT scan of the chest and abdomen and total body PET-CT scan.
•Tumor must be amenable to curative resection (curative resection can include pelvic exenteration).
•No history of invasive rectal malignancy, regardless of disease-free interval.
•No other rectal cancers (i.e., sarcoma, lymphoma, carcinoid, squamous cell carcinoma, or cloacogenic carcinoma) or synchronous colon cancer.
•No clear indication of involvement of the pelvic side walls by imaging.
•Age between 18 and 75 years.
•ECOG Performance status \< 2 if age \< 70 years and = 0 if age 71-75 years.

Exclusion Criteria

•Previous treatment with oxaliplatin, irinotecan or bevacizumab. Previous 5-fluorouracil or capecitabine treatment is allowed.
•Previous pelvic radiation therapy.
•Hepatic disease that would preclude study treatment or follow-up; uncontrolled coagulopathy; history of viral hepatitis or other chronic liver disease.
•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.
•Lack of upper gastrointestinal tract integrity or malabsorption syndrome; active inflammatory bowel disease (i.e., patients requiring current medical interventions or who are symptomatic).
•Pregnant or lactating women. Fertile patients must use effective contraception (i.e double-barrier contraceptive measures, oral contraception or avoidance of intercourse during the study and for 30 days after surgery).
•Patients with prior malignancies (with the exception of rectal cancer), including invasive colon cancer, are eligible provided they have been disease-free for ≥ 5 years and are deemed by their physician to be at low risk for recurrence.
•Other malignancy within the past 5 years with the exception of effectively treated squamous cell or basal cell skin cancer, melanoma in situ, carcinoma in situ of the cervix, or carcinoma in situ of the colon or rectum.
•Known hypersensitivity to fluorouracil, oxaliplatin or irinotecan or to Chinese hamster ovary cell proteins.
•Clinically significant peripheral neuropathy (i.e., neurosensory or neuromotor toxicity ≥ grade 2).

Arms & Interventions

Single Arm

INDUCTION TREATMENT WITH FOLFOXIRI PLUS BEVACIZUMAB FOLLOWED BY PREOPERATIVE CHEMORADIOTHERAPY PLUS BEVACIZUMAB

Intervention: FOLFOXIRI plus Bevacizumab

Single Arm

INDUCTION TREATMENT WITH FOLFOXIRI PLUS BEVACIZUMAB FOLLOWED BY PREOPERATIVE CHEMORADIOTHERAPY PLUS BEVACIZUMAB

Intervention: Chemoradiotherapy plus Bevacizumab

Outcomes

Primary Outcomes

Disease-free survival rate at 2 years

Time Frame: Up to 2 years

Disease-free survival is defined as time from study entry until progression of disease (according to RECIST 1.1) or death from any cause. Patients who are alive without having progressed at the end of the study will be censored at their last radiological assessment.