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An Open Label, Single-Centre, Phase II Study for Radiosensitization of AVASTIN® (Bevacizumab) With Stereotactic Body Radiotherapy (SBRT) for Colorectal Liver Metastasis (SBRT Avastin)

Phase 2
18 Years
Open (Enrolling)
Colorectal Cancer.

Thank you

Trial Information

An Open Label, Single-Centre, Phase II Study for Radiosensitization of AVASTIN® (Bevacizumab) With Stereotactic Body Radiotherapy (SBRT) for Colorectal Liver Metastasis (SBRT Avastin)

This is a single-centre, single-arm open-label proof-of-concept study to analyze the imaging
(DCE-CT,CEUS and Quantitative US) effects of neoadjuvant bevacizumab and SBRT on colorectal
metastases to the liver. Patients will receive 2 doses of bevacizumab 5mg/kg IV prior to
SBRT. The second dose of bevacizumab will be given 2 weeks after the first dose of
bevacizumab and within 48 hours of starting the first dose of SBRT. The SBRT prescription
dose will be up to 60 Gy in 6 fractions, delivered on alternating weekdays for 2 weeks.
Total SBRT dose will be determined by size of target lesion, liver sparing and
organs-at-risk dose constraints. DCE-CT, CEUS and Quantitative US will be performed within 7
days prior to the first dose of bevacizumab, after the second dose of bevacizumab and within
7 days of completing SBRT.

Inclusion Criteria:

1. Histological and/or cytological diagnosis of colorectal cancer with liver metastases
confirmed on imaging scans

2. 1-3 liver metastatic lesions confirmed on imaging scans

3. Maximum size of target metastatic lesion is 6 cm or less

4. At least 700 cc of liver uninvolved by tumour

5. Previous liver resection, systemic therapy or local ablation therapy is allowed.
Extrahepatic disease is allowed if maximum involved organs (including the liver) is 3
or less (i.e. oligometastases).

6. Child-Pugh's A liver function

7. Male or female: Age ≥ 18 years

8. Life expectancy > 3 months

9. ECOG PS < 2

10. Prior bevacizumab is permitted as long as last dose >28 days from registration

11. Laboratory Requirements - within 7 days prior to registration: Hematology

- neutrophils ≥ 1.5 x 109/L

- platelets ≥ 100 x 109/L

- hemoglobin ≥ 90 g/L Biochemistry

- bilirubin ≤ 1.5 x upper limit of normal

- serum creatinine ≤ 1.5 x upper limit of normal

- AST ≤ 3 x upper limit of normal (≤ 5 x if liver metastases present)

- ALT ≤ 3 x upper limit of normal (≤ 5 x if liver metastases present)

- INR ≤ 1.3 Urinalysis

- Proteinuria ≤ grade 1 (by dipstick)

12. Patients are willing to provide informed consent.

13. Patients must be accessible for treatment and follow up. Patients registered on this
trial must be treated and followed at the participating centre

Exclusion Criteria:

1. Major surgical procedure, open biopsy or significant traumatic injury within 28 days
prior to registration (i.e. patients must have recovered to less than or equal to
grade 1 from any major surgery), or anticipation of need for major surgical procedure
during or within 7 weeks after chemo-radiotherapy.

2. Known to have clinical or radiological evidence of CNS metastases.

3. Patients with a past or current history (within last 2 years) of other malignancies,
except for the indication under this study and curatively treated basal and squamous
skin cancer or in-situ cancer of the cervix. Prior treatment of localized prostate
cancer is permitted if treatment was greater than 5 years ago and the patient
currently has no biochemical evidence of recurrence.

4. Active hepatitis (infectious or non-infectious)

5. Patients with known history or present encephalopathy

6. Gross clinically detectable ascites

7. Women of childbearing potential with a positive pregnancy test at baseline or
lactating. Postmenopausal women must have been amenorrheic for at least 12 months to
be considered of non childbearing potential. Females patients must not be pregnant or
become pregnant during this study and for 6 months after the last dose of

8. Sexually active males and females (of childbearing potential) unwilling to practice
contraception during the study. Patients of childbearing potential must be willing to
use a reliable method of birth control. i.e.:double barrier method, oral
contraceptive, implant, dermal contraception, long-term injectable contraceptive,
intrauterine device or tubal ligation during the study.

9. Prior radiotherapy to the right upper quadrant of the liver

10. Known hypersensitivity reaction to bevacizumab

11. Known hypersensitivity to Chinese hamster ovary cell products or other recombinant
human or humanised antibodies

12. Uncontrolled hypertension, defined as SBP > 150/100 on more than one occasion that
does not respond to therapy with antihypertensive agents or being treated with more
than 2 anti-hypertensive medications.

13. Any other serious intercurrent illness such as cardiovascular disease, HIV or any
neurological disease.

14. Patients taking other approved or investigational drug/anticancer treatment (other
than ongoing androgen ablation and oral prednisone which are permitted) during the
study period, including chemotherapy, biological response modifiers, immunotherapy,
surgery or radiotherapy.

15. Patients concurrently participating in another clinical trial

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Tumor perfusion

Outcome Description:

Tumor perfusion as measured by DCE-CT

Outcome Time Frame:

day 24

Safety Issue:


Principal Investigator

Yoo-Joung Ko, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Sunnybrook Health Sciences Centre


Canada: Health Canada

Study ID:




Start Date:

March 2012

Completion Date:

June 2013

Related Keywords:

  • Colorectal Cancer.
  • Colorectal
  • Colorectal Neoplasms
  • Neoplasm Metastasis