Trial Outcomes & Findings for Study of Bevacizumab/Doxil in Treatment of Platinum-Resistant/Refractory Ovarian Cancer (CA) (NCT NCT00945139)

Last Updated: 2015-07-31

Results Overview

Tumor response is evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.0). Target lesions are assessed by hysical exam and/or computerized tomography (CT): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient decrease in the sum of the longest diameter of target lesions to qualify for PR nor sufficient increase in the sum of the longest diameter of target lesions to qualify for Progressive Disease; Progressive Disease (PD), 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

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

46 participants

Primary outcome timeframe

Up to 25 months

Results posted on

2015-07-31

Participant Flow

A total of 60 patients were screened for this study at all sites beginning March 2007. 46 patients were enrolled at the UNM Cancer Center, NYU Medical Center and NM Cancer Care Associates/Santa Fe.

Participant milestones

Participant milestones
Measure	Doxil (PLD) + Avastin (Bevacizumab) Open label study of Doxil given as 30 mg/m2 every three weeks by itself in cycle 1, and then followed by Avastin 15 mg/kg on cycle 2 and every cycle thereafter until disease progression (Progression-Free Survival determination) or withdrawal for other causes (unacceptable toxicity, patient preference). Patients undergoing PK determinations will have the dose of Avastin on cycle 2 given 24 hours after Doxil.
Overall Study STARTED	46
Overall Study COMPLETED	46
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study of Bevacizumab/Doxil in Treatment of Platinum-Resistant/Refractory Ovarian Cancer (CA)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Doxil (PLD) + Avastin (Bevacizumab) n=46 Participants Open label study of Doxil given as 30 mg/m2 every three weeks by itself in cycle 1, and then followed by Avastin 15 mg/kg on cycle 2 and every cycle thereafter until disease progression (Progression-Free Survival determination) or withdrawal for other causes (unacceptable toxicity, patient preference). Patients undergoing PK determinations will have the dose of Avastin on cycle 2 given 24 hours after Doxil.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	10 Participants n=5 Participants
Age, Categorical >=65 years	36 Participants n=5 Participants
Sex: Female, Male Female	46 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 25 months

Population: 43 out of 46 enrolled patients were assessable for PFS by RECIST criteria. The remaining patients could not be evaluated for this endpoint because of missed imaging scans that prevented analysis according to the defined criteria.

Outcome measures

Outcome measures
Measure	Doxil (PLD) + Avastin (Bevacizumab) n=43 Participants Treatment was administered every 3 weeks (bevacizumab 15 mg/kg beginning on cycle 2 and PLD 30 mg/m2).
Progression Free Survival (PFS) by RECIST Criteria	7.8 Months Interval 2.0 to 13.3

PRIMARY outcome

Timeframe: Up to 25 months

Population: 28 out of 46 enrolled patients were assessable for PFS per GCIC criteria. The remaining patients could not be evaluated for this endpoint because the timing of their CA-125 measurements did not meet the defined criteria.

Using GCIC criteria, progression is defined as CA-125 levels greater than, or equal to, 2 times the upper limit of a reference range on 2 occasions and at least 1 week apart.

Outcome measures

Outcome measures
Measure	Doxil (PLD) + Avastin (Bevacizumab) n=28 Participants Treatment was administered every 3 weeks (bevacizumab 15 mg/kg beginning on cycle 2 and PLD 30 mg/m2).
Progression Free Survival (PFS) by GCIC Criteria	6.6 Months Interval 1.0 to 24.6

SECONDARY outcome

Timeframe: 4 years

The time from treatment initiation to death by any cause

Outcome measures

Outcome measures
Measure	Doxil (PLD) + Avastin (Bevacizumab) n=46 Participants Treatment was administered every 3 weeks (bevacizumab 15 mg/kg beginning on cycle 2 and PLD 30 mg/m2).
Overall Survival	33.2 Months Interval 3.0 to 37.5

SECONDARY outcome

Timeframe: 3 years

ORR is the sum of the percentages of patients achieving complete and partial responses. Tumor response is evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.0)

Outcome measures

Outcome measures
Measure	Doxil (PLD) + Avastin (Bevacizumab) n=43 Participants Treatment was administered every 3 weeks (bevacizumab 15 mg/kg beginning on cycle 2 and PLD 30 mg/m2).
Overall Response Rate (ORR) by RECIST Complete Response (CR)	9 Percentage of participants Interval 3.0 to 22.0
Overall Response Rate (ORR) by RECIST Partial Response (PR)	21 Percentage of participants Interval 10.0 to 36.0
Overall Response Rate (ORR) by RECIST Overall Response Rate (ORR)	30 Percentage of participants Interval 17.0 to 46.0

SECONDARY outcome

Timeframe: 3 years

Clinical Benefit Rate (CBR) is the sum of the percentages of patients achieving complete response, partial response, and stable disease. Tumor response is evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.0). Target lesions are assessed by physical exam and/or computerized tomography (CT): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient decrease in the sum of the longest diameter of target lesions to qualify for PR nor sufficient increase in the sum of the longest diameter of target lesions to qualify for Progressive Disease; Progressive Disease (PD), 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

Outcome measures

Outcome measures
Measure	Doxil (PLD) + Avastin (Bevacizumab) n=43 Participants Treatment was administered every 3 weeks (bevacizumab 15 mg/kg beginning on cycle 2 and PLD 30 mg/m2).
Clinical Benefit Rate (by RECIST) Complete Response (CR)	9 percentage of participants Interval 3.0 to 22.0
Clinical Benefit Rate (by RECIST) Partial Response (PR)	21 percentage of participants Interval 10.0 to 36.0
Clinical Benefit Rate (by RECIST) Stable Disease (SD)	56 percentage of participants Interval 40.0 to 71.0
Clinical Benefit Rate (by RECIST) Clinical Benefit Rate (CBR)	86 percentage of participants Interval 72.0 to 95.0

SECONDARY outcome

Timeframe: 3 years

A response according to GCIC criteria has occurred if there is at least a 50% reduction in CA 125 levels from a pretreatment sample. The response must be confirmed and maintained for at least 28 days. Patients can be evaluated according to CA-125 only if they have a pretreatment sample that is at least twice the upper limit of normal and within 2 weeks prior to starting treatment.

Outcome measures

Outcome measures
Measure	Doxil (PLD) + Avastin (Bevacizumab) n=28 Participants Treatment was administered every 3 weeks (bevacizumab 15 mg/kg beginning on cycle 2 and PLD 30 mg/m2).
Overall Response Rate (ORR) by GCIC Criteria	50 percentage of participants Interval 31.0 to 69.0

Adverse Events

Doxil (PLD) + Avastin (Bevacizumab)

Serious events: 3 serious events

Other events: 45 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Doxil (PLD) + Avastin (Bevacizumab) n=46 participants at risk Treatment was administered every 3 weeks (bevacizumab 15 mg/kg beginning on cycle 2 and PLD 30 mg/m2).
Gastrointestinal disorders Nausea	2.2% 1/46 • Number of events 1 • 3 years
Gastrointestinal disorders Vomiting	2.2% 1/46 • Number of events 1 • 3 years
Gastrointestinal disorders Dehydration	2.2% 1/46 • Number of events 1 • 3 years
Infections and infestations Bladder Infection	2.2% 1/46 • Number of events 1 • 3 years
Musculoskeletal and connective tissue disorders Muscle weakness	2.2% 1/46 • Number of events 1 • 3 years
Nervous system disorders Cognitive disturbance	2.2% 1/46 • Number of events 1 • 3 years
Nervous system disorders Headache	2.2% 1/46 • Number of events 1 • 3 years
Nervous system disorders Speech impairment: global aphasia	2.2% 1/46 • Number of events 1 • 3 years
Respiratory, thoracic and mediastinal disorders Pleural effusion	2.2% 1/46 • Number of events 1 • 3 years
Gastrointestinal disorders Esophagoscopy abnormal: ulceration	2.2% 1/46 • Number of events 1 • 3 years

Other adverse events

Other adverse events
Measure	Doxil (PLD) + Avastin (Bevacizumab) n=46 participants at risk Treatment was administered every 3 weeks (bevacizumab 15 mg/kg beginning on cycle 2 and PLD 30 mg/m2).
General disorders Allergic reaction	8.7% 4/46 • Number of events 4 • 3 years
Blood and lymphatic system disorders Hemoglobin decreased	13.0% 6/46 • Number of events 9 • 3 years
Blood and lymphatic system disorders Leukocyte count decreased	10.9% 5/46 • Number of events 11 • 3 years
Blood and lymphatic system disorders Neutrophil count decreased	13.0% 6/46 • Number of events 8 • 3 years
Blood and lymphatic system disorders Platelet count decreased	8.7% 4/46 • Number of events 7 • 3 years
Cardiac disorders Hypertension (High blood pressure)	39.1% 18/46 • Number of events 34 • 3 years
General disorders Fatigue	50.0% 23/46 • Number of events 40 • 3 years
General disorders Fever	6.5% 3/46 • Number of events 3 • 3 years
Metabolism and nutrition disorders Weight Loss	10.9% 5/46 • Number of events 7 • 3 years
Skin and subcutaneous tissue disorders Skin disorders - Other	15.2% 7/46 • Number of events 9 • 3 years
Skin and subcutaneous tissue disorders Dry skin	26.1% 12/46 • Number of events 13 • 3 years
Skin and subcutaneous tissue disorders Hand-and-foot syndrome	45.7% 21/46 • Number of events 76 • 3 years
Skin and subcutaneous tissue disorders Hyperpigmentation	15.2% 7/46 • Number of events 8 • 3 years
Skin and subcutaneous tissue disorders Rash	32.6% 15/46 • Number of events 22 • 3 years
Skin and subcutaneous tissue disorders Desquamating rash	10.9% 5/46 • Number of events 9 • 3 years
Gastrointestinal disorders Abdominal distension	8.7% 4/46 • Number of events 5 • 3 years
Gastrointestinal disorders Abdominal pain	30.4% 14/46 • Number of events 20 • 3 years
Gastrointestinal disorders Constipation	32.6% 15/46 • Number of events 22 • 3 years
Gastrointestinal disorders Diarrhea	17.4% 8/46 • Number of events 13 • 3 years
Gastrointestinal disorders Dyspepsia (Indigestion)	6.5% 3/46 • Number of events 4 • 3 years
Gastrointestinal disorders Mucositis - oral (Mouth inflammation)	19.6% 9/46 • Number of events 16 • 3 years
Gastrointestinal disorders Nausea	37.0% 17/46 • Number of events 32 • 3 years
Gastrointestinal disorders Vomiting	13.0% 6/46 • Number of events 12 • 3 years
Gastrointestinal disorders Anorexia (Loss of appetite)	17.4% 8/46 • Number of events 11 • 3 years
Gastrointestinal disorders Dehydration	6.5% 3/46 • Number of events 3 • 3 years
Infections and infestations Urinary tract infection	13.0% 6/46 • Number of events 8 • 3 years
General disorders Edema: limbs	8.7% 4/46 • Number of events 5 • 3 years
Investigations Hyperglycemia (High blood glucose)	19.6% 9/46 • Number of events 17 • 3 years
Investigations Hypocalcemia (Low calcium levels)	8.7% 4/46 • Number of events 4 • 3 years
Investigations Hypokalemia (Low potassium levels)	10.9% 5/46 • Number of events 8 • 3 years
Investigations Hypomagnesemia (Low magnesium levels)	6.5% 3/46 • Number of events 5 • 3 years
Investigations Hyponatremia (Low sodium levels)	17.4% 8/46 • Number of events 13 • 3 years
Investigations Creatinine increased	10.9% 5/46 • Number of events 8 • 3 years
Investigations Proteinuria	8.7% 4/46 • Number of events 6 • 3 years
Musculoskeletal and connective tissue disorders Back pain	8.7% 4/46 • Number of events 6 • 3 years
Musculoskeletal and connective tissue disorders Joint pain	6.5% 3/46 • Number of events 3 • 3 years
Musculoskeletal and connective tissue disorders Myalgia (Muscle pain)	6.5% 3/46 • Number of events 4 • 3 years
Musculoskeletal and connective tissue disorders Pain in extremity	10.9% 5/46 • Number of events 8 • 3 years
Musculoskeletal and connective tissue disorders Pain - Other	17.4% 8/46 • Number of events 9 • 3 years
Nervous system disorders Dizziness	8.7% 4/46 • Number of events 4 • 3 years
Nervous system disorders Headache	43.5% 20/46 • Number of events 31 • 3 years
Nervous system disorders Peripheral sensory neuropathy	23.9% 11/46 • Number of events 15 • 3 years
Nervous system disorders Anxiety	10.9% 5/46 • Number of events 6 • 3 years
Nervous system disorders Depression	6.5% 3/46 • Number of events 3 • 3 years
Eye disorders Blurred vision	6.5% 3/46 • Number of events 5 • 3 years
Respiratory, thoracic and mediastinal disorders Cough	15.2% 7/46 • Number of events 9 • 3 years
Respiratory, thoracic and mediastinal disorders Dyspnea (Shortness of breath)	13.0% 6/46 • Number of events 6 • 3 years
Respiratory, thoracic and mediastinal disorders Epistaxis (Nosebleed)	21.7% 10/46 • Number of events 14 • 3 years
Respiratory, thoracic and mediastinal disorders Voice alteration	6.5% 3/46 • Number of events 6 • 3 years
Renal and urinary disorders Urinary frequency	10.9% 5/46 • Number of events 5 • 3 years
General disorders Ear, nose and throat examination abnormal	30.4% 14/46 • Number of events 18 • 3 years

Additional Information

Dr. Claire Verschraegen

University of Vermont CC

Phone: 802-656-5487

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place