A Study of Avastin (Bevacizumab) With XELOX or FOLFOX in Patients With Metastatic Colorectal Cancer and Disease Progression Under First-line FOLFIRI and Avastin

Colorectal Cancer Clinical Trial

Official title:

A Single-arm Open-label Phase II Study: Treatment Beyond Progression by Adding Bevacizumab to XELOX or FOLFOX Chemotherapy in Patients With Metastatic Colorectal Cancer and Disease Progression Under First-line FOLFIRI + Bevacizumab Combination

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01077739
• Other study ID #: ML22519
• Secondary ID: 2009-012090-36
• Status: Completed
• Phase: Phase 2
• First received: February 26, 2010
• Last updated: December 8, 2014
• Start date: July 2009
• Est. completion date: January 2012

Study information

• Verified date: December 2014
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicines and Health Products, FAMHP
• Study type: Interventional

Clinical Trial Summary

This open-label single arm study will evaluate the efficacy and safety of Avastin added to XELOX or FOLFOX in patients with metastatic colorectal cancer and disease progression on 1st line therapy with FOLFIRI plus Avastin. Patients will receive either Avastin (7.5mg/kg iv infusion every 3 weeks) and standard XELOX (Xeloda [capecitabine] plus oxaliplatin) chemotherapy or Avastin (5 mg/kg iv infusion every 2 weeks) and standard FOLFOX (5-FU and leucovorin plus oxaliplatin) chemotherapy. The anticipated time on study treatment is until disease progression, and the target sample size is 100 individuals.

Other known NCT identifiers

• NCT01069679

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: January 2012
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• adult patients >/=18 years of age

• metastatic colorectal cancer

• at least 1 measurable lesion according to RECIST v. 1.1

• patients with disease progression with prior FOLFIRI + Avastin therapy who are not candidates for primary metastasectomy

• disease progression </= 8 weeks after last dose of Avastin

• ECOG </=2

• No more than 8 weeks between 1st-line treatment with FOLFIRI + Avastin and 2nd-line treatment with XELOX or FOLFOX + Avastin

Exclusion Criteria:

• disease progression > 8 weeks after last Avastin administration

• clinically significant cardiovascular disease

• CNS disease except for treated brain metastasis

• history of other malignancies within 2 years prior to start of study treatment (with the exception of curatively treated basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix)

• major surgery, open biopsy, or significant traumatic injury within 28 days prior to start of study treatment

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms
• Disease Progression

Intervention

Drug:
• fluorouracil (5FU)
standard FOLFOX regimen
• leucovorin
standard FOLFOX regimen
• bevacizumab [Avastin]
7.5 mg/kg iv infusion every 3 weeks OR 5 mg/kg iv infusion every 2 weeks
• capecitabine [Xeloda]
standard XELOX regimen
• oxaliplatin
standard XELOX or FOLFOX regimen

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival (PFS) From the Start of Treatment Beyond Progression	PFS from the start of treatment beyond progression was defined as the interval between the start of beyond-progression therapy and the date at which disease progression was documented. Progression of disease was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1 and abdominal/pelvic computerized tomography (CT) or magnetic resonance imaging (MRI) scanning as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. The same method of assessment and the same technique were to be used to evaluate each lesion throughout the entire study. If more than one method was used, data from the most accurate method according to RECIST were recorded. Median PFS was estimated using the Kaplan-Meier method.	Baseline, every 9 weeks until disease progression, at end of treatment or withdrawal, for up to 24 months	No
Secondary	PFS From the Start of First-Line Therapy	PFS from the start of first-line therapy was defined as the interval between the start of first-line therapy and the date at which second disease progression (after the start of beyond progression therapy) was documented. Progression of disease was evaluated using RECIST version 1.1 and abdominal/pelvic CT or MRI scanning. The same method of assessment and the same technique were to be used to evaluate each lesion throughout the entire study. If more than one method was used, data from the most accurate method according to RECIST were recorded. Median PFS was estimated using the Kaplan-Meier method.	Baseline, every 9 weeks until disease progression, at end of treatment or withdrawal, for up to 24 months	No
Secondary	Percentage of Participants With an Overall Response of Complete Response (CR) or Partial Response (PR)	Percentage of participants with an overall response of CR or PR according to RECIST criteria.; CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must have decreased to normal (short axis less than [<]10 millimeters [mm]). No new lesions. PR was defined as greater than or equal to (=)30 percent (%) decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.	Baseline, every 9 weeks until disease progression, at end of treatment or withdrawal, for up to 24 months	No
Secondary	Geometric Mean Values of Pro-Angiogenic Cytokine Concentrations at Baseline and Prior to Progression	Pro-angiogenic cytokine concentrations of placental growth factor (PlGF), basic fibroblast growth factor (bFGF), and hepatocyte growth factor (HGF) in participant sera were measured and reported in units of picograms/milliliter (pg/mL). The geometric mean was calculated as exp10 (mean of log10 transformed concentration) and the standard deviation (SD) is SD of log10 transformed concentration.	Baseline, every 9 weeks until disease progression, at final visit or at withdrawal, for up to 24 months	No