Folfoxiri Plus Bevacizumab Followed by Chemoradiotherapy Plus Bevacizumab in Patients With Resectable Rectal Cancer

NCT03085992 | Completed Phase 2 DMC

• 2 other identifiers: TRUST2011-003340-45
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 4

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.

Conditions

Rectal Cancer

Keywords

rectal cancer; FOLFOXIRI; bevacizumab; trust

Outcome Measures

Primary Outcomes (1)

• Disease-free survival rate at 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.

  Up to 2 years

Secondary Outcomes (4)

• Response rate

  Up to 2 years

• Toxicity Rate

  Up to 2 years

• Overall survival

  Up to 2 years

• Pathological complete response rate

  Up to 2 years

Study Arms (1)

Single Arm

EXPERIMENTAL

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

Drug: FOLFOXIRI plus Bevacizumab; Other: Chemoradiotherapy plus Bevacizumab

Interventions

FOLFOXIRI plus Bevacizumab DRUG

* BEVACIZUMAB 5 mg/kg over 30 minutes, day 1 * IRINOTECAN 165 mg/sqm IV over 1-h, day 1 * OXALIPLATIN 85 mg/sqm IV over 2-h, day 1 * L-LEUCOVORIN 200 mg/sqm IV over 2-h, day 1 * 5-FLUOROURACIL 3200 mg/sqm IV 48-h continuous infusion, starting on day 1 administered every two weeks for 6 cycles (3 months).

Single Arm

Chemoradiotherapy plus Bevacizumab OTHER

* FLUOROURACIL 225 mg/sqm/day by protracted IV continuous infusion or -CAPECITABINE 825 mg/sqm/bid p.o. continuously without interruption for all the duration of radiation treatment; * EXTERNAL-BEAM IRRADIATION 50.4 GY in 28 daily fractions over 5.5 weeks; * BEVACIZUMAB 5 mg/kg over 30 minutes, starting on day 1 of radiation treatment day 1 and then every two weeks (for 3 cycles).

Single Arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Life expectancy of at least 5 years (excluding diagnosis of cancer).
• Hematopoietic: absolute neutrophil count ≥ 1,000/mm3; platelet count ≥ 100,000/mm3; haemoglobin level ≥ 10 g/dL.
• Hepatic: total bilirubin ≤ 1.5 times upper limit of normal (ULN); alkaline phosphatase ≤ 2 times ULN; AST ≤ 2 times ULN. \[Note: \*If AST\>ULN, serologic testing for Hepatitis B and C must be negative\].
• Renal: creatinine clearance \> 50 mL/min; no renal disease that would preclude study treatment or follow-up.
• Written informed consent to experimental treatment and pharmacogenomic analyses.

You may not qualify if:

• 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).
• Psychiatric or addictive disorders, or other conditions that, in the opinion of the investigator, would preclude study participation

Sponsors & Collaborators

• Azienda Ospedaliero, Universitaria Pisana: lead

Study Sites (4)

Irccs Istituto Oncologico Veneto

Padua, 35128, Italy

Location

Polo Oncologico Area Vasta Nord Ovest

Pisa, 56100, Italy

Location

ausl5 di Pisa

Pontedera, 56100, Italy

Location

Dipartimento Oncologico AUSL 7

Siena, 53100, Italy

Location

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Bevacizumab; Chemoradiotherapy

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Combined Modality Therapy; Therapeutics; Drug Therapy; Radiotherapy

Study Officials

• Alfredo Falcone, MD

  Polo Oncologico Area Vasta Nord Ovest

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Study Record Dates

• First Submitted: June 8, 2016
• First Posted: March 22, 2017
• Study Start: March 1, 2012
• Primary Completion: July 1, 2017
• Study Completion: March 12, 2018
• Last Updated: March 14, 2018

Record last verified: 2018-03

Locations

IT (4)