Neoadjuvant Bevacizumab, Capecitabine and Radiation Therapy With or Without Oxaliplatin Locally Advanced Rectal Cancer

NCT00828672 | Completed Phase 2 Results DMC

• 3 other identifiers: s51104 - ML51942007-007177-23MO19051
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 9

Brief Summary

Phase II clinical trial, open-label, randomized, two arms, multicentre (possibly multinational). Academic, investigator initiated. To assess the activity of bevacizumab (AvastinTM) in combination with capecitabine (XelodaTM) and radiation therapy with or without oxaliplatin (EloxatinTM) in the pre-operative treatment of locally advanced rectal cancer, followed by TME (total mesorectal excision).

Conditions

Locally Advanced Rectal Cancer

Keywords

bevacizumab; capecitabine; radiation therapy; oxaliplatin; multimodality treatments; TME (total mesorectal excision); Axe Beam; rectal cancer; neoadjuvant; pathological complete response; postoperative complications

Outcome Measures

Primary Outcomes (1)

• Pathologic Response at Surgery. Overview of Complete Pathologic Responses, Good and Little Tumour Regression Rates at Surgery.

  Dworak tumour regression grades (TRG) were used to assess pathologic response: TRG0=no regression. TRG1=dominant tumor mass with obvious fibrosis and/or vasculopathy; TRG2=dominant fibrotic changes with few tumour cells or groups; TRG3=very few (difficult to find microscopically) tumour cells in fibrotic tissue with or without mucus substance. TRG4=no intact viable tumour cells, only fibrotic mass or presence of mucin lakes without associated malignant cells (total tumour regression). Pathologic assessments of tumour response post chemoradiotherapy as provided by investigators (read by local pathologists on operative specimens) were reviewed centrally for all pts for whom surgical materials were available (centrally reviewed set). The diagnosis of independent central reviewers primed. Pathologic complete response rates (TRG4) are reported (%). Good (TRG3 and TRG4 together) and little (TRG 0,1 and 2) tumour regression rates are summarized. For these 2 last rows, % add to 100.

  4 months

Secondary Outcomes (6)

• Number of Participants With Histopathologic R0 and Negative CRM Resection

  4 months

• Number of Participants With Pathologic Complete Response at Surgery. Number of Participants With Good or Little Pathological Tumour Regression at Surgery.

  4 months

• Clinical Response Rate

  3 months

• Types and Numbers of Adverse Events - General Overview

  continuous up to 1 year

• Recurrence Rates and Disease Free Survival

  up to 5 years

Study Arms (2)

AXE (ARM 1)

ACTIVE COMPARATOR

Oxaliplatin, Bevacizumab and Capecitabine concurrently with radiotherapy.

Drug: Oxaliplatin; Drug: Bevacizumab; Drug: Capecitabine; Radiation: radiotherapy

AX (ARM 2)

ACTIVE COMPARATOR

Bevacizumab and Capecitabine concurrently with radiotherapy

Drug: Bevacizumab; Drug: Capecitabine; Radiation: radiotherapy

Interventions

Oxaliplatin DRUG

Administered on days 15,22,29,36 en 43; 50 mg/m2

Also known as: Eloxatin

AXE (ARM 1)

Bevacizumab DRUG

Administered on days 1,15,29 and 43 ; 5mg/kg

Also known as: Avastin

AX (ARM 2); AXE (ARM 1)

Capecitabine DRUG

825 mg/m2 ; 25 days - 5days per week, concurrent with radiotherapy

Also known as: Xeloda

AX (ARM 2); AXE (ARM 1)

radiotherapy RADIATION

Total dose 45Gy

AX (ARM 2); AXE (ARM 1)

Eligibility Criteria

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

You may qualify if:

• Adenocarcinoma of rectum measurable (RECIST), locally advanced (defined by MRI - Tumour beyond mesorectal fascia (T4) or Tumour ≤ 2 mm from mesorectal fascia or T3 tumour \< 5 cm from anal verge
• Patient is at least 18 years of age
• Good organ function

You may not qualify if:

• Evidence of distant metastases
• Contraindication for bevacizumab
• Pregnant or breastfeeding women.

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead

Study Sites (9)

Onze Lieve Vrouwziekenhuis

Aalst, 9300, Belgium

Location

ZNA Middelheim

Antwerp, ZNA Middelheim, Belgium

Location

AZ St- Lucas

Bruges, 8310, Belgium

Location

Erasme Hospital

Brussels, 1070, Belgium

Location

Cliniques Universitaires St Luc

Brussels, 1200, Belgium

Location

AZ Groeninge

Kortrijk, 8500, Belgium

Location

C.H.U. Sart-Tilman

Liège, 4000, Belgium

Location

Clinique Sainte Elisabeth

Namur, 5000, Belgium

Location

H. Hartziekenhuis

Roeselare, 8800, Belgium

Location

MeSH Terms

Conditions

Rectal Neoplasms; Postoperative Complications

Interventions

Oxaliplatin; Bevacizumab; Capecitabine; Radiotherapy

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; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Therapeutics

Limitations and Caveats

The study was not powered to allow for formal statistical comparisons between arms

Results Point of Contact

• Title: Prof. Dr. Eric Van Cutsem
• Organization: UZ Leuven

Eric.VanCutsem@uzleuven.be

+32 16 34 42 18

Study Officials

• Eric Van Cutsem, Prof. Dr.

  UZ Leuven

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: January 23, 2009
• First Posted: January 26, 2009
• Study Start: June 1, 2009
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2019
• Last Updated: July 10, 2019
• Results First Posted: July 10, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

BE (9)