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

Locally Advanced Rectal Cancer Clinical Trial

— AXEBEAM  

Official title:

A Randomized Phase II Study of Bevacizumab, Capecitabine and Radiation Therapy With or Without Oxaliplatin in the Preoperative Treatment of Locally Advanced Rectal Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00828672
• Other study ID #: s51104 - ML5194
• Secondary ID: 2007-007177-23MO
• Status: Completed
• Phase: Phase 2
• Start date: June 2009
• Est. completion date: March 2019

Study information

• Verified date: July 2019
• Source: Universitaire Ziekenhuizen Leuven
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Description:

See Synopsis

Recruitment information / eligibility

• Status: Completed
• Enrollment: 84
• Est. completion date: March 2019
• Est. primary completion date: March 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• Evidence of distant metastases

• Contraindication for bevacizumab

• Pregnant or breastfeeding women.

Related Conditions & MeSH terms

• Locally Advanced Rectal Cancer
• Rectal Neoplasms

Intervention

Drug:
• Oxaliplatin
Administered on days 15,22,29,36 en 43; 50 mg/m2
• Bevacizumab
Administered on days 1,15,29 and 43 ; 5mg/kg
• Capecitabine
825 mg/m2 ; 25 days - 5days per week, concurrent with radiotherapy

Radiation:
• radiotherapy
Total dose 45Gy

Locations

Country	Name	City	State
Belgium	Onze Lieve Vrouwziekenhuis	Aalst
Belgium	ZNA Middelheim	Antwerp
Belgium	AZ St- Lucas	Brugge
Belgium	Cliniques Universitaires St Luc	Brussels
Belgium	Erasme Hospital	Brussels
Belgium	AZ Groeninge	Kortrijk
Belgium	C.H.U. Sart-Tilman	Liege
Belgium	Clinique Sainte Elisabeth	Namur
Belgium	H. Hartziekenhuis	Roeselare

Sponsors (1)

Lead Sponsor	Collaborator
Universitaire Ziekenhuizen Leuven

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Number of Participants With Histopathologic R0 and Negative CRM Resection	Histopathologic R0 resection rate was defined as margins histologically negative for tumour involvement after resection. The circumferential resection margin (CRM) is considered to be involved if microscopic tumour is present <1mm from or at the inked circumferential or radial resection margin. Data on quality of mesorectal excision were expected but not collected consistently.	4 months
Secondary	Number of Participants With Pathologic Complete Response at Surgery. Number of Participants With Good or Little Pathological Tumour Regression 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	Clinical Response Rate	Baseline tumour measurements were performed within 4 weeks prior to treatment start (RECIST). The same methods of assessment (CT and/or MRI) were used for each measurable lesion at baseline and during follow-up.; Complete Response (CR) is disappearance of all clinical and radiological evidence of tumour (both target and non-target lesions).; Partial Response (PR) is at least a 30% decrease in the sum of LD of target lesions, taking as reference the baseline sum of tumour longest diameters (LD).; Stable Disease (SD) is steady state of disease. Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.; Progressive Disease (PD) is at least a 20% increase in the sum of LD of measured lesions taking as references the smallest sum LD recorded since the treatment started. Appearance of new lesions constitutes PD. In exceptional circumstances, unequivocal progression of non-target lesions was considered evidence of PD.	3 months
Secondary	Types and Numbers of Adverse Events - General Overview	Adverse events graded as per NCI CTCAE (US National Cancer Institute Common Terminology Criteria for Adverse Events) version 3.0. All Serious Adverse Events occurrences are reported and counts are summarized here; all Adverse Events (all grades) related and not related to study treatment are reported and summarized here; all severe laboratory events (hematology and biochemistry Gr 3 and higher) are reported and summarized here; all severe postoperative complications (Gr 3 and higher) occurred within the first month post surgery are reported and summarized here. See section Adverse events for details.	continuous up to 1 year
Secondary	Recurrence Rates and Disease Free Survival	Counts and proportions of patients experiencing recurrence of disease (local and distant).	up to 5 years
Secondary	Death Rates and Overall Survival	Counts and proportions of patients deceased (post-study).	up to 5 years