Bevacizumab With Pelvic Radiotherapy And Primary Chemotherapy in Patients With Poor-Risk Rectal Cancer

NCT01481545 | Completed Phase 2 Results

• 2 other identifiers: BRANCH2008-003989-26
• Study Type: interventional
• Target: 62
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to evaluate the use of chemotherapy, radiation therapy and bevacizumab before surgery in patients with locally advanced rectal cancer (LARC).

Conditions

Rectal Cancer

Keywords

locally advanced; high risk; preoperative therapy

Outcome Measures

Primary Outcomes (1)

• Percentage of Patients With Complete Tumor Regression Rate (TRG1)

  Complete tumor regression rate (TRG1) was the ratio of patients with TRG1, graded at surgical resection, and total patients included in the study, expressed in percentage. Tumor regression grade (TRG) was misured according to the Mandard Scale. Briefly,TRG1 was a complete tumor regression (regardless of the presence of acellular mucine lakes), and TRG2 was a nearly complete tumor regression with extensive fibrosis; TRG3 presented with clear evidence of residual cancer cells but with predominant fibrosis;TRG4 was a residual of cancer cells outgrowing fibrosis; TRG5 was the absence of regressive changes.

  In 8 weeks after completion of chemoradiotherapy

Secondary Outcomes (6)

• Number of Participants With Adverse Events

  Up to 8 weeks after surgery

• Number of Patients With Sphincter Preservation

  In 8 weeks after chemoradiation therapy

• Progression Free Survival (PFS)

  10 years

• Overall Survival (OS)

  10 years

• Clinical Response Rate

  7 weeks after chemoradiation therapy up to 11 weeks

Study Arms (1)

preoperative chemoradiotherapy

EXPERIMENTAL

Preoperative radiation therapy and combination chemotherapy plus bevacizumab

Radiation: Radiation therapy; Drug: Oxaliplatin; Drug: Raltitrexed; Drug: levofolinic acid; Drug: 5-fluorouracil; Drug: Bevacizumab

Interventions

Radiation therapy RADIATION

Radiation therapy will be administered at the total dose of 45 Gy, given with five weekly fractions over a period of 5 weeks. The daily fraction dose will be 1.8 Gy

preoperative chemoradiotherapy

Oxaliplatin DRUG

100 mg/m2 on day 1 every 2 weeks for 3 cycles (for patients with resectable organ metastases (M1), an additional 2 cycles of chemotherapy will be given after radiation therapy)

preoperative chemoradiotherapy

Raltitrexed DRUG

2.5 mg/m2 on day 1 every 2 weeks for 3 cycles (for patients with resectable organ metastases (M1) , an additional 2 cycles of chemotherapy will be given after radiation therapy)

preoperative chemoradiotherapy

levofolinic acid DRUG

250 mg/m2 on day 2 every 2 weeks for 3 cycles (for patients with resectable organ metastases (M1), an additional 2 cycles of chemotherapy will be given after radiation therapy)

preoperative chemoradiotherapy

5-fluorouracil DRUG

800 mg/m2 on day 2 every 2 weeks for 3 cycles (for patients with resectable organ metastases (M1), an additional 2 cycles of chemotherapy will be given after radiation therapy)

preoperative chemoradiotherapy

Bevacizumab DRUG

will be given by intravenous infusion at the dose of 5 mg/kg concurrent with chemotherapy and radiotherapy every 2 weeks for 4 cycles from -14 days to start chemo-radiotherapy (classical schedule) or 4 days before the concurrent administration of chemotherapy and radiation therapy for 2 cycles if the number of TRG1 was not reached in the first stage (statistical design) with the classical schedule (for patients with resectable organ metastases (M1), one additional administration of bevacizumab will be given after radiation therapy)

preoperative chemoradiotherapy

Eligibility Criteria

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

You may qualify if:

• Patients with histologically or cytologically confirmed diagnosis of locally advanced rectal cancer (LARC) at high risk of recurrence (T4, N+, T3N0 with tumor located in the lower third of the rectum and/or circumferential resection margin (CRM) £5 mm), or LARC with resectable organ metastasis (M1).
• Age 18 years or older
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
• Life expectancy of at least 12 weeks
• Measurable and/or evaluable (resectable organ metastasis)lesions according to RECIST criteria
• Neutrophils \> 1500 and Platelets \> 100,000 /L
• Total bilirubin \< or = 1.5 time the upper-normal limits (UNL) of the Institutional normal values and ASAT (SGOT) and/or ALAT (SGPT) \< or = 2.5 x UNL, or \< or = 5 x UNL in case of liver metastases, alkaline phosphatase \< or = 2.5 x UNL, or \< or = 5 x UNL in case of liver metastases.
• Creatinine clearance \> 50 mL/min or serum creatinine \< or = 1.5 x UNL
• Urine dipstick of proteinuria \< 2+. Patients discovered to have \> or = 2+ proteinuria on dipstick urinalysis at baseline, should undergo a 24-hour urine collection and must demonstrate \< or = 1 g of protein/24 hr.
• Written informed consent.
• Patients must be accessible for treatment and follow up. Patients registered on this trial must be treated and followed at the participating Center

You may not qualify if:

• Prior radiotherapy or chemotherapy for rectal cancer.
• Untreated brain metastases or spinal cord compression or primary brain tumours
• History or evidence upon physical examination of CNS disease unless adequately treated (e.g., seizure not controlled with standard medical therapy or history of stroke).
• History of inflammatory bowel disease and/or acute/subacute bowel occlusion
• Serious, non-healing wound, ulcer, or bone fracture
• Evidence of bleeding diathesis or coagulopathy.
• Uncontrolled hypertension
• Clinically significant (i.e. active) cardiovascular disease, for example cerebrovascular accidents (≤ 6 months), myocardial infarction (≤ 6 months), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication
• Current or recent (within 10 days prior to study treatment start) ongoing treatment with anticoagulants for therapeutic purposes.
• Chronic, daily treatment with high-dose aspirin (\>325 mg/day) or other medications known to predispose to gastrointestinal ulceration.
• Treatment with any investigational drug within 30 days prior to enrolment.
• Patients with known allergy to Chinese hamster ovary cell proteins, or any of the components of the study medications
• Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of basal and squamous cell carcinoma or cervical cancer in situ
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start, or anticipation of the need for major surgical procedure during the course of the study.
• Pregnant or lactating women. Women of childbearing potential with either a positive or no pregnancy test at baseline. Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential. Sexually active males and females (of childbearing potential) unwilling to practice contraception during the study.

Sponsors & Collaborators

• National Cancer Institute, Naples: lead

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Radiotherapy; Oxaliplatin; raltitrexed; Leucovorin; Fluorouracil; Bevacizumab

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)

Therapeutics; Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Antonio Avallone
• Organization: National Cancer Institute of Naples

a.avallone@istitutotumori.na.it

+39 081 5903629

Study Officials

• Antonio Avallone, M.D.

  National Cancer Institute, Naples

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 11, 2011
• First Posted: November 29, 2011
• Study Start: December 1, 2006
• Primary Completion: July 1, 2011
• Study Completion: December 1, 2016
• Last Updated: February 3, 2021
• Results First Posted: February 3, 2021

Record last verified: 2020-09