A Study of First Line Treatment With Avastin (Bevacizumab) in Combination With Carboplatin and Weekly Paclitaxel in Patients With Ovarian Cancer

A Single-arm Phase II Clinical Study Investigating the Addition of Bevacizumab to Carboplatin and Weekly Paclitaxel as First-line Treatment in Patients With Epithelial Ovarian Cancer

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00937560

Enrollment

190

Registered

2009-07-13

Start date

2009-06-25

Completion date

2013-07-01

Last updated

2017-11-06

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

Conditions

Ovarian Cancer

Brief summary

This single arm study evaluated the efficacy and safety of first-line chemotherapy with carboplatin and dose-dense weekly paclitaxel plus bevacizumab (Avastin) in participants with epithelial ovarian, fallopian tube, or primary peritoneal cancer. Participants received 6-8 3-week cycles of treatment with bevacizumab 7.5 mg/kg intravenously (iv) on Day 1 of each cycle, paclitaxel 80 mg/m\^2 iv on days 1, 8, and 15 of each cycle, and carboplatin iv to an area under the curve (AUC) of 6 on day 1 of each cycle. Following combination chemotherapy, bevacizumab could be continued to be given as a monotherapy.

Interventions

DRUGBevacizumab

Bevacizumab was supplied as a sterile solution for infusion.

DRUGPaclitaxel

Paclitaxel was supplied locally in commercial batches.

DRUGCarboplatin

Carboplatin was supplied locally in commercial batches.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

FEMALE

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Female patients, ≥ 18 years of age. * Epithelial ovarian, fallopian tube, or primary peritoneal cancer. * Initial surgery, but no chemotherapy or radiotherapy. * Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

Exclusion criteria

* Non-epithelial tumors. * Ovarian tumors with low malignant potential. * Previous systemic anti-cancer therapy for ovarian cancer. * History or evidence of synchronous primary endometrial cancer. * Current or recent daily treatment with aspirin (\> 325mg/day) or with full dose anticoagulant or thrombolytic agents for therapeutic purposes.

Design outcomes

Primary

Measure	Time frame	Description
Progression-free Survival	Baseline to the data cut-off date of 19 Jul 2012 for analysis of the primary Outcome Measure (follow-up time up to 3 years, 1 month)	Progression-free survival was defined as the time from the first administration of any study treatment to the first disease progression using Response Evaluation Criteria In Solid Tumors (RECIST) or death from any cause, whichever occurred first.

Secondary

Measure	Time frame	Description
Percentage of Participants With an Objective Response	Baseline to the data cut-off date of 19 Jul 2012 for analysis of the primary Outcome Measure (follow-up time up to 3 years, 1 month)	An objective response was defined as either a complete response (CR) or a partial response (PR). Using the Response Evaluation Criteria in Solid Tumors (RECIST), a CR was defined as the disappearance of all target lesions and all non-target lesions, normalization of tumor marker level, and no new lesions and a PR was defined as the disappearance of all target lesions and persistence of ≥ 1 non-target lesions and/or the maintenance of tumor marker level above the normal limits, or, at least a 30% decrease in the sum of the longest diameter of target lesions, and no new lesions or unequivocal progression of existing non-target lesions. Only participants with measurable disease were included in the analysis according to RECIST only. Only participants with a Baseline ovarian cancer mucin CA-125 level ≥ 2 times the upper limit of normal who had a ≥ 50% reduction of CA-125 from Baseline were included in the analysis according to CA-125 level.
Duration of Response	Baseline to the data cut-off date of 19 Jul 2012 for analysis of the primary Outcome Measure (follow-up time up to 3 years, 1 month)	Duration of response was defined as the interval between the date of the first documented response by RECIST to the date of first disease progression or death, whichever occurred earlier. Disease progression was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of 1 or more new lesions or the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. Only participants with measurable disease were included in the analysis according to RECIST only. Only participants with a Baseline ovarian cancer mucin CA-125 level ≥ 2 times the upper limit of normal who had a ≥ 50% reduction of CA-125 from Baseline were included in the analysis according to CA-125 level.
Overall Survival at 1 Year and 2 Years	Baseline to Year 2	Reported are the percentage of participants that were alive at 1 year and 2 years after enrolling in the study.
Biological Progression-free Interval	Baseline to the data cut-off date of 19 Jul 2012 for analysis of the primary Outcome Measure (follow-up time up to 3 years, 1 month)	Biological progression-free interval is defined as the interval from the date of the first administration of any study treatment to the date of the first documented serial elevation of the ovarian cancer mucin CA-125. More precisely, this is defined as the first documented increase in CA-125 levels as follows: (1) CA-125 greater than or equal to 2 times the upper level of normal (ULN) on 2 occasions at least 1 week apart (for patients with CA-125 within normal range pre-treatment) or (2) CA-125 greater than or equal to 2 times the ULN on 2 occasions at least 1 week apart (for patients with elevated CA-125 pre-treatment and initial normalisation of CA-125 on-treatment) or (3) CA-125 greater than or equal to 2 times the nadir value, which is the lowest observed CA-125 value per patient on 2 occasions at least 1 week apart (for patients with elevated CA-125 pre-treatment which never normalised).

Countries

Brazil, France, Italy, Netherlands, Norway, Russia, Spain, Sweden, United Kingdom

Participant flow

Participants by arm

Arm	Count
Bevacizumab + Paclitaxel + Carboplatin Participants received 6-8 (at the investigator's discretion) 3-week cycles of bevacizumab 7.5 mg/kg IV on Day 1 of each cycle, paclitaxel 80 mg/m\^2 IV on Days 1, 8, and 15 of each cycle, and carboplatin IV to an AUC of 6 on Day 1 of each cycle. The initial dose of carboplatin was calculated according to the Calvert formula (mg = \[GFR + 25\] x 6). Following the initial treatment (bevacizumab + paclitaxel + carboplatin) period, participants received additional 3-week cycles of monotherapy bevacizumab 7.5 mg/kg IV during the maintenance treatment period. The total maximum bevacizumab treatment duration was 17 cycles, (12 months) which included both the initial treatment period and the bevacizumab monotherapy maintenance treatment period.	189
Total	189

Arm

Count

Bevacizumab + Paclitaxel + Carboplatin

Participants received 6-8 (at the investigator's discretion) 3-week cycles of bevacizumab 7.5 mg/kg IV on Day 1 of each cycle, paclitaxel 80 mg/m\^2 IV on Days 1, 8, and 15 of each cycle, and carboplatin IV to an AUC of 6 on Day 1 of each cycle. The initial dose of carboplatin was calculated according to the Calvert formula (mg = \[GFR + 25\] x 6). Following the initial treatment (bevacizumab + paclitaxel + carboplatin) period, participants received additional 3-week cycles of monotherapy bevacizumab 7.5 mg/kg IV during the maintenance treatment period. The total maximum bevacizumab treatment duration was 17 cycles, (12 months) which included both the initial treatment period and the bevacizumab monotherapy maintenance treatment period.

189

Total

189

Withdrawals & dropouts

Period	Reason	FG000
Initial Treatment	Adverse Event	1
Initial Treatment	Death	6
Initial Treatment	Lost to Follow-up	1
Initial Treatment	No end of study page	10
Initial Treatment	Withdraw consent	3
Maintenance Treatment	According to protocol	1
Maintenance Treatment	Death	12
Maintenance Treatment	Withdraw consent	5

Baseline characteristics

Characteristic	Bevacizumab + Paclitaxel + Carboplatin
Age, Continuous	55 years
Sex: Female, Male Female	189 Participants
Sex: Female, Male Male	0 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	186 / 189
serious Total, serious adverse events	43 / 189

Outcome results

Primary

Progression-free Survival

Progression-free survival was defined as the time from the first administration of any study treatment to the first disease progression using Response Evaluation Criteria In Solid Tumors (RECIST) or death from any cause, whichever occurred first.

Time frame: Baseline to the data cut-off date of 19 Jul 2012 for analysis of the primary Outcome Measure (follow-up time up to 3 years, 1 month)