Symptoms and General Pathology

All Conditions

Neoplasms

Digestive System Diseases

Postoperative Complications

Rectal Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Intestinal Diseases

Rectal Diseases

Antineoplastic Agents

All Drugs and Chemicals

Capecitabine

Bevacizumab

Oxaliplatin

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Antimetabolites

Oxaliplatin, Bevacizumab and Capecitabine concurrently with radiotherapy.

Bevacizumab and Capecitabine concurrently with radiotherapy

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

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

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

radiotherapy

Eric Van Cutsem, Prof. Dr.

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).

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

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

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.

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.

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.

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.

Counts and proportions of patients experiencing recurrence of disease (local and distant).

Counts and proportions of patients deceased (post-study).

Universitaire Ziekenhuizen KU Leuven

All SAE occurences are reported and displayed below. Only Gr 3-4-5 adverse events (serious and non serious) are reported in this report.

Oxaliplatin, Bevacizumab and Capecitabine concurrently with radiotherapy.

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

Radiotherapy: Total dose 45Gy

AXE (ARM 1)

Bevacizumab and Capecitabine concurrently with radiotherapy

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

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

Radiotherapy: Total dose 45Gy

AX (ARM 2)

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

ECOG PS=0

ECOG PS=1

ECOG PS = 0 Fully active, able to carry on all pre-disease performance without restriction; ECOG PS = 1 Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work

ECOG PS (Performance Status)

<5cm

>=5cm

Distance from tumour to anal verge measured during colonoscopy (in cm).

Distance from tumour to anal verge

<2mm

>=2mm

Distance to CRM

T2 (Tumor invades muscularis propria)

T3 (tumor invades into pericolorectal tissues)

T4 (tumor invades through peritoneum/other organs)

Tumour staging was done using clinical, radiological and pathological assessments on rectal biopsies. Tumors (T) were graded using the colon and rectum cancer staging (TNM, American Joint Committee on Cancer 7th edition) where T2 tumors are less severe then T3 tumors and T4 tumors respectively.

Tumour stage

N0 (no regional lymph node metastase)

N1 (metastasis in 1-3 regional lymp nodes)

N2 (metastasis in 4 or more regional lymph nodes)

Nx (regional nodes cannot be assessed)

Nodal staging was done using clinical, radiological and pathological assessments where applicable. Lymph node involvement (N) was graded using the colon and rectum cancer staging (TNM, American Joint Committee on Cancer 7th edition) where N0 is no regional lymph node involved and N1 is less severe then N2 involvement.

Nodal stage

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

Prof. Dr. Eric Van Cutsem

Pathological complete response (Dworak TRG=4) %

Good tumour regression (Dworak TRG=3-4) %

Little tumour regression (Dworak TRG=0-1-2) %

Patients who had undertaken surgery and had pathology materials available for central review (centrally reviewed subset)

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

Negative resection margins

Positive resection margins

Patient in Arm 2 that discontinued chemoradiotherapy due to major toxicity and had surgery off protocol is counted here as well

Number of Participants With Histopathologic R0 and Negative CRM Resection

Complete response, no tumour left Dworak TRG=4

Good tumour regression TRG=3-4

No or little tumour regression Dworak TRG=0-1-2

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Neoadjuvant Bevacizumab, Capecitabine and Radiation Therapy With or Without Oxaliplatin Locally Advanced Rectal Cancer	NCT00828672	Locally Advance...	Oxaliplatin Bevacizumab Capecitabine radiotherapy	18 Years -	Universitaire Ziekenhuizen KU Leuven
Neoadjuvant Bevacizumab, Capecitabine and Radiation Therapy With or Without Oxaliplatin Locally Advanced Rectal Cancer	NCT00828672	Locally Advance...	Oxaliplatin Bevacizumab Capecitabine radiotherapy	18 Years -	Universitaire Ziekenhuizen KU Leuven
Neoadjuvant Bevacizumab, Capecitabine and Radiation Therapy With or Without Oxaliplatin Locally Advanced Rectal Cancer	NCT00828672	Locally Advance...	Oxaliplatin Bevacizumab Capecitabine radiotherapy	18 Years -	Universitaire Ziekenhuizen KU Leuven

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