A Study of Avastin (Bevacizumab) in Combination With Xelox and Tarceva in Patients With Metastatic Colorectal Cancer.

An Open-label Study of the Effect of First-line Treatment With Avastin+Xelox, Followed by Avastin+Tarceva, on Progression-free Survival in Patients With Metastatic Colorectal Cancer

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01135498

Enrollment

Registered

2010-06-02

Start date

2006-11-30

Completion date

2010-04-30

Last updated

2015-02-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Colorectal Cancer

Brief summary

This study will evaluate the efficacy and safety of a first-line regimen of Avastin and Xelox (Xeloda + Eloxatin) followed by Avastin and Tarceva, in patients with metastatic colorectal cancer. Patients will receive 6 x 21 day cycles of treatment with Avastin (7.5mg/kg iv on day 1), Xeloda (1000mg/m2 po twice daily on days 1 to 14) and Eloxatin (130mg/m2 iv on day 1). Patients free of disease progression will then continue with Avastin (7.5mg/kg iv once every 3 weeks) and Tarceva (150mg po daily). The anticipated time on study treatment is until disease progression, and the target sample size is \<100 individuals.

Interventions

DRUGbevacizumab [Avastin]

Intravenous repeating dose

DRUGeloxatin

Intravenous repeating dose

DRUGcapecitabine [Xeloda]

Oral repeating dose

DRUGerlotinib [Tarceva]

Oral repeating dose

Study design

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* adult patients, \>=18 years of age; * adenocarcinoma of colon or rectum, with metastatic disease; * \>=1 measurable lesion.

Exclusion criteria

* previous treatment with Avastin or Tarceva; * previous systemic treatment for advanced or metastatic disease; * adjuvant treatment for non-metastatic disease in past 6 months.

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants With Disease Progression or Death	Start of study to approximately 4 years	Disease progression was defined according to Response Evaluation Criteria in Solid Tumors (RECIST) as a 20 percent (%) increase in the sum of the longest diameter of target lesions, or a measureable increase in a non-target lesion, or the appearance of new lesions.
Progression-Free Survival	From study start up to approximately 4 years	Progression-free survival was defined as the time from the date of informed consent until the date when the participant had progression of disease or died from disease progression. Participants who received surgical treatment after treatment ended were censored at the time of surgery. Participants who left the study for reasons other than progression of the disease were censored on the date on which they received a later antitumor therapy (with the same or different drugs, radiotherapy, or surgery).

Secondary

Measure	Time frame	Description
Percentage of Participants Achieving Objective Response (Complete Response [CR] or Partial Response [PR])	From study start up to approximately 4 years	Percentage of participants with objective response based assessment of CR or PR according to Response Evaluation Criteria in Solid Tumors (RECIST). 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 \[mm\]) and 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.
Percentage of Participants Achieving Disease Control (CR, PR, or No Change [NC])	From study start up to approximately 4 years	Percent of participants with confirmed CR, PR, or NC. Per RECIST version (v)1.0: CR was defined as disappearance of all target and non-target lesions. PR was defined as ≥30% decrease in sum of longest diameters of target lesions taking as reference baseline sum longest diameters associated to non-progressive disease response for non-target lesions. NC was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease taking as reference smallest sum of longest dimensions since treatment started associated to non-progressive disease response for non-target lesions.
Percentage of Participants Who Died	From study start up to approximately 4 years	—
Overall Survival (OS)	From study start up to approximately 4 years	Overall survival was defined as the time from the date of informed consent to the date of death (regardless of the cause of death). There was no restriction; survival was calculated until the date of death, even if another line of treatment was received, or until the date censored (last contact with the participant even if drugs different from the study treatment schedule were received). For all participants, survival information was collected until the date of death, the last contact, or the last follow-up.

Countries

Spain

Participant flow

Participants by arm

Arm	Count
Bevacizumab+Oxaliplatin+Capecitabine/Bevacizumab+Erlotinib Cycles 1-6 (3-week cycles): participants received bevacizumab 7.5 mg/kg IV and oxaliplatin 130 mg/m\^2 IV on Day 1 and capecitabine 1000 mg/m\^2, tablet, PO, every 12 hours on Days 1 through 14. The cycle was repeated every 21 days for a maximum of 6 cycles. Cycles 7 and beyond (3-week cycles): If all 6 cycles were tolerated with no disease progression, participants then received bevacizumab 7.5 mg/kg IV on Day 1 and erlotinib 150 mg tablets, PO, once daily. This cycle was repeated every 3 weeks until disease progression.	90
Total	90

Arm

Count

Bevacizumab+Oxaliplatin+Capecitabine/Bevacizumab+Erlotinib

Cycles 1-6 (3-week cycles): participants received bevacizumab 7.5 mg/kg IV and oxaliplatin 130 mg/m\^2 IV on Day 1 and capecitabine 1000 mg/m\^2, tablet, PO, every 12 hours on Days 1 through 14. The cycle was repeated every 21 days for a maximum of 6 cycles. Cycles 7 and beyond (3-week cycles): If all 6 cycles were tolerated with no disease progression, participants then received bevacizumab 7.5 mg/kg IV on Day 1 and erlotinib 150 mg tablets, PO, once daily. This cycle was repeated every 3 weeks until disease progression.

Total

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	20
Overall Study	Death	1
Overall Study	Investigator judgement	25
Overall Study	Ongoing at time of analysis	2
Overall Study	Progressive disease	38
Overall Study	Withdrawal by Subject	4

Baseline characteristics

Characteristic	Bevacizumab+Oxaliplatin+Capecitabine/Bevacizumab+Erlotinib
Age, Continuous	59.23 years STANDARD_DEVIATION 8.18
Sex: Female, Male Female	29 Participants
Sex: Female, Male Male	61 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	89 / 90
serious Total, serious adverse events	33 / 90

Outcome results

Primary

Percentage of Participants With Disease Progression or Death

Disease progression was defined according to Response Evaluation Criteria in Solid Tumors (RECIST) as a 20 percent (%) increase in the sum of the longest diameter of target lesions, or a measureable increase in a non-target lesion, or the appearance of new lesions.

Time frame: Start of study to approximately 4 years

Population: ITT population

Arm	Measure	Value (NUMBER)
Bevacizumab+Oxaliplatin+Capecitabine/Bevacizumab+Erlotinib	Percentage of Participants With Disease Progression or Death	61.1 percentage of participants

Primary

Progression-Free Survival

Progression-free survival was defined as the time from the date of informed consent until the date when the participant had progression of disease or died from disease progression. Participants who received surgical treatment after treatment ended were censored at the time of surgery. Participants who left the study for reasons other than progression of the disease were censored on the date on which they received a later antitumor therapy (with the same or different drugs, radiotherapy, or surgery).