A Randomized Phase II Study of Bevacizumab, Capecitabine and Radiation Therapy With or Without Oxaliplatin in the Preoperative Treatment of Locally Advanced Rectal Cancer
Overview
- Phase
- Phase 2
- Intervention
- Bevacizumab
- Conditions
- Locally Advanced Rectal Cancer
- Sponsor
- Universitaire Ziekenhuizen KU Leuven
- Enrollment
- 84
- Locations
- 9
- Primary Endpoint
- Pathologic Response at Surgery. Overview of Complete Pathologic Responses, Good and Little Tumour Regression Rates at Surgery.
- Status
- Completed
- Last Updated
- 6 years ago
Overview
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).
Detailed Description
See Synopsis
Investigators
Eligibility Criteria
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.
Arms & Interventions
AX (ARM 2)
Bevacizumab and Capecitabine concurrently with radiotherapy
Intervention: Bevacizumab
AXE (ARM 1)
Oxaliplatin, Bevacizumab and Capecitabine concurrently with radiotherapy.
Intervention: Oxaliplatin
AXE (ARM 1)
Oxaliplatin, Bevacizumab and Capecitabine concurrently with radiotherapy.
Intervention: Bevacizumab
AXE (ARM 1)
Oxaliplatin, Bevacizumab and Capecitabine concurrently with radiotherapy.
Intervention: Capecitabine
AXE (ARM 1)
Oxaliplatin, Bevacizumab and Capecitabine concurrently with radiotherapy.
Intervention: radiotherapy
AX (ARM 2)
Bevacizumab and Capecitabine concurrently with radiotherapy
Intervention: Capecitabine
AX (ARM 2)
Bevacizumab and Capecitabine concurrently with radiotherapy
Intervention: radiotherapy
Outcomes
Primary Outcomes
Pathologic Response at Surgery. Overview of Complete Pathologic Responses, Good and Little Tumour Regression Rates at Surgery.
Time Frame: 4 months
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.
Secondary Outcomes
- 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)
- Death Rates and Overall Survival(up to 5 years)