Radiosensitization of AVASTIN® (Bevacizumab) With Stereotactic Body Radiotherapy for Colorectal Liver Metastasis

NCT01569984 | Completed Phase 2

• 1 other identifier: OZM-032
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Colorectal Cancer.

Keywords

Colorectal

Outcome Measures

Primary Outcomes (1)

• Tumor perfusion

  Tumor perfusion as measured by DCE-CT

  day 24

Secondary Outcomes (1)

• Blood flow

  Day 24

Study Arms (1)

Avastin, SBRT

EXPERIMENTAL

2 treatments of avastin followed by 6 treatments of SBRT every other day.

Radiation: Stereotactic body radiotherapy

Interventions

Stereotactic body radiotherapy RADIATION

Avastin 7.5 mg/kg IV x 2 doses 14 days apart

Also known as: Bevacizumab

Avastin, SBRT

Eligibility Criteria

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

You may qualify if:

• Histological and/or cytological diagnosis of colorectal cancer with liver metastases confirmed on imaging scans
• liver metastatic lesions confirmed on imaging scans
• Maximum size of target metastatic lesion is 6 cm or less
• At least 700 cc of liver uninvolved by tumour
• 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).
• Child-Pugh's A liver function
• Male or female: Age ≥ 18 years
• Life expectancy \> 3 months
• ECOG PS \< 2
• Prior bevacizumab is permitted as long as last dose \>28 days from registration
• 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

You may not qualify if:

• 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.
• Known to have clinical or radiological evidence of CNS metastases.
• 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.
• Active hepatitis (infectious or non-infectious)
• Patients with known history or present encephalopathy
• Gross clinically detectable ascites
• 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 bevacizumab.
• 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.
• Prior radiotherapy to the right upper quadrant of the liver
• Known hypersensitivity reaction to bevacizumab
• Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanised antibodies
• 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.
• Any other serious intercurrent illness such as cardiovascular disease, HIV or any neurological disease.
• 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.
• Patients concurrently participating in another clinical trial

Sponsors & Collaborators

• Dr. Yoo-Joung Ko: lead
• Roche Pharma AG: collaborator

Study Sites (1)

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Radiosurgery; Bevacizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Yoo-Joung Ko, MD

  Sunnybrook Health Sciences Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Medical Oncoolgist

Study Record Dates

• First Submitted: March 30, 2012
• First Posted: April 3, 2012
• Study Start: March 1, 2012
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: October 13, 2016

Record last verified: 2016-10

Locations

CA (1)