Trial Outcomes & Findings for Study of AMG 479 as Second Line Therapy in Patients With Recurrent Platinum-sensitive Ovarian Cancer (NCT NCT00719212)
NCT ID: NCT00719212
Last Updated: 2016-01-11
Results Overview
RECIST(v1.0):CR:disappearance of all target lesions or disappearance of all nontarget lesions \& normalization of tumor marker level/•PR:at least 30% decrease in the sum of the longest diam(LD) of target les° taking as ref the baseline sum LD OR CR for target les° \& incomplete response/SD for nontarget les°. CR \& PR to be confirmed no less than 4 wks after initial doc of response.The def of the resp acc to serum CA125 level was as per GCIGCA125 criteria: * PR:elevated CA125 at baseline PR considered if a ≥ 50% decrease compared to baseline value was observed on 2 consecutive assessmts drawn at least 1 wk apart * CR:elevated CA125 at baseline CR was def with 2 CA125 values below ULN observed on 2 consecutive assessmts drawn at least 1 wk apart A pt was considered to have a best overall resp of:CR:if CR as per RECIST \& CA125 /-PR: if CR as per RECIST \& PR as per CA125 OR CR as per RECIST and SD as per CA125 with elevated CA125 at baseline OR PR as per RECIST \& CR/PR or SD as per CA125
COMPLETED
PHASE2
61 participants
Radiological Tumor assessment: Every 9 (+/- 1 ) weeks during study treatment until documentation of progression or end of study treatment + confirmation PR or CR no less than 4 weeks after initial documentation of response + CA 125: Day 1 of each cycle
2016-01-11
Participant Flow
The study was conducted over a total of 35 sites in 7 countries.
Participant milestones
| Measure |
AMG 479
AMG 479 administered on day 1 of each 21-day cycle up to disease progression, unacceptable toxicity, withdrawal of consent or sponsor decision to stop the study.
AMG 479: Solution for infusion - 18 mg/kg on day 1 of each 21-day cycle
|
|---|---|
|
Overall Study
STARTED
|
61
|
|
Overall Study
COMPLETED
|
17
|
|
Overall Study
NOT COMPLETED
|
44
|
Reasons for withdrawal
| Measure |
AMG 479
AMG 479 administered on day 1 of each 21-day cycle up to disease progression, unacceptable toxicity, withdrawal of consent or sponsor decision to stop the study.
AMG 479: Solution for infusion - 18 mg/kg on day 1 of each 21-day cycle
|
|---|---|
|
Overall Study
Death
|
41
|
|
Overall Study
Lost to Follow-up
|
2
|
|
Overall Study
Withdrawal by Subject
|
1
|
Baseline Characteristics
Study of AMG 479 as Second Line Therapy in Patients With Recurrent Platinum-sensitive Ovarian Cancer
Baseline characteristics by cohort
| Measure |
AMG 479
n=61 Participants
AMG 479 administered on day 1 of each 21-day cycle up to disease progression, unacceptable toxicity, withdrawal of consent or sponsor decision to stop the study.
AMG 479: Solution for infusion - 18 mg/kg on day 1 of each 21-day cycle
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
39 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
22 Participants
n=5 Participants
|
|
Age, Continuous
|
61.8 years
STANDARD_DEVIATION 10.4 • n=5 Participants
|
|
Sex: Female, Male
Female
|
61 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
18 participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
7 participants
n=5 Participants
|
|
Region of Enrollment
Germany
|
4 participants
n=5 Participants
|
|
Region of Enrollment
France
|
24 participants
n=5 Participants
|
|
Region of Enrollment
Ireland
|
7 participants
n=5 Participants
|
|
Region of Enrollment
Israel
|
1 participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group Performance Status (ECOG PS)
PS 0 (fully active)
|
41 participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group Performance Status (ECOG PS)
PS 1 (restricted in physically strenuous activity)
|
20 participants
n=5 Participants
|
|
Time from initial diagnosis to registration
|
20.4 Months
STANDARD_DEVIATION 6.2 • n=5 Participants
|
|
Origin of tumor
Primary Peritoneal
|
5 participants
n=5 Participants
|
|
Origin of tumor
Fallopian Tube
|
3 participants
n=5 Participants
|
|
Origin of tumor
Ovarian
|
46 participants
n=5 Participants
|
|
Origin of tumor
Ovarian + Primary Peritoneal
|
3 participants
n=5 Participants
|
|
Origin of tumor
Ovarian + Fallopian Tube
|
4 participants
n=5 Participants
|
|
Stage at First Diagnosis (International Federation of Gynecology and Obstetrics (FIGO) )
IC
|
3 participants
n=5 Participants
|
|
Stage at First Diagnosis (International Federation of Gynecology and Obstetrics (FIGO) )
IIA
|
1 participants
n=5 Participants
|
|
Stage at First Diagnosis (International Federation of Gynecology and Obstetrics (FIGO) )
IIB
|
2 participants
n=5 Participants
|
|
Stage at First Diagnosis (International Federation of Gynecology and Obstetrics (FIGO) )
IIC
|
2 participants
n=5 Participants
|
|
Stage at First Diagnosis (International Federation of Gynecology and Obstetrics (FIGO) )
IIIA
|
1 participants
n=5 Participants
|
|
Stage at First Diagnosis (International Federation of Gynecology and Obstetrics (FIGO) )
IIIB
|
3 participants
n=5 Participants
|
|
Stage at First Diagnosis (International Federation of Gynecology and Obstetrics (FIGO) )
IIIC
|
44 participants
n=5 Participants
|
|
Stage at First Diagnosis (International Federation of Gynecology and Obstetrics (FIGO) )
IV
|
5 participants
n=5 Participants
|
|
Histopathologic Type
Papillary serous
|
42 participants
n=5 Participants
|
|
Histopathologic Type
Mucinous
|
2 participants
n=5 Participants
|
|
Histopathologic Type
Endometroid
|
5 participants
n=5 Participants
|
|
Histopathologic Type
Clear cell
|
4 participants
n=5 Participants
|
|
Histopathologic Type
Mixed
|
2 participants
n=5 Participants
|
|
Histopathologic Type
Other
|
6 participants
n=5 Participants
|
|
Histologic Grade (G)
G1 (well differentiated)
|
1 participants
n=5 Participants
|
|
Histologic Grade (G)
G2 (moderately differentiated)
|
6 participants
n=5 Participants
|
|
Histologic Grade (G)
G3 (poorly differentiated)
|
45 participants
n=5 Participants
|
|
Histologic Grade (G)
Not done
|
9 participants
n=5 Participants
|
|
CA 125 status
With elevated CA 125 only
|
5 participants
n=5 Participants
|
|
CA 125 status
With elevated CA 125 + Non target lesion(s) only
|
11 participants
n=5 Participants
|
|
CA 125 status
With elevatCA125+target lesions+/-nontargetlesions
|
37 participants
n=5 Participants
|
|
CA 125 status
With CA125normal+target lesions+/-nontargetlesions
|
8 participants
n=5 Participants
|
|
Number of prior therapies
1 therapy
|
2 participants
n=5 Participants
|
|
Number of prior therapies
2 therapies
|
38 participants
n=5 Participants
|
|
Number of prior therapies
3 therapies
|
16 participants
n=5 Participants
|
|
Number of prior therapies
4 therapies
|
3 participants
n=5 Participants
|
|
Number of prior therapies
5 therapies
|
2 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Radiological Tumor assessment: Every 9 (+/- 1 ) weeks during study treatment until documentation of progression or end of study treatment + confirmation PR or CR no less than 4 weeks after initial documentation of response + CA 125: Day 1 of each cyclePopulation: Intent To Treat
RECIST(v1.0):CR:disappearance of all target lesions or disappearance of all nontarget lesions \& normalization of tumor marker level/•PR:at least 30% decrease in the sum of the longest diam(LD) of target les° taking as ref the baseline sum LD OR CR for target les° \& incomplete response/SD for nontarget les°. CR \& PR to be confirmed no less than 4 wks after initial doc of response.The def of the resp acc to serum CA125 level was as per GCIGCA125 criteria: * PR:elevated CA125 at baseline PR considered if a ≥ 50% decrease compared to baseline value was observed on 2 consecutive assessmts drawn at least 1 wk apart * CR:elevated CA125 at baseline CR was def with 2 CA125 values below ULN observed on 2 consecutive assessmts drawn at least 1 wk apart A pt was considered to have a best overall resp of:CR:if CR as per RECIST \& CA125 /-PR: if CR as per RECIST \& PR as per CA125 OR CR as per RECIST and SD as per CA125 with elevated CA125 at baseline OR PR as per RECIST \& CR/PR or SD as per CA125
Outcome measures
| Measure |
AMG 479
n=61 Participants
AMG 479 administered on day 1 of each 21-day cycle up to disease progression, unacceptable toxicity, withdrawal of consent or sponsor decision to stop the study.
AMG 479: Solution for infusion - 18 mg/kg on day 1 of each 21-day cycle
|
|---|---|
|
Objective Response Rate (ORR) Investigator Assessment: % of Patients in the Group Who Achieve a Complete Response(CR) or Partial Response(PR) According to RECIST Criteria and GCIG CA125 Response Criteria. - Assessments of the Response by the Investigators
|
1.6 percentage of patients
Interval 0.0 to 8.8
|
PRIMARY outcome
Timeframe: Radiological Tumor assessment: Every 9 (+/- 1 ) weeks during study treatment until documentation of progression or end of study treatment + confirmation PR or CR no less than 4 weeks after initial documentation of response + CA 125: Day 1 of each cyclePopulation: Intent To Treat
RECIST(v1.0):CR:disappearance of all target lesions or disappearance of all nontarget lesions \& normalization of tumor marker level/•PR:at least 30% decrease in the sum of the longest diam(LD) of target les° taking as ref the baseline sum LD OR CR for target les° \& incomplete response/SD for nontarget les°. CR \& PR to be confirmed no less than 4 wks after initial doc of response.The def of the resp acc to serum CA125 level was as per GCIGCA125 criteria: * PR:elevated CA125 at baseline PR considered if a ≥ 50% decrease compared to baseline value was observed on 2 consecutive assessmts drawn at least 1 wk apart * CR:elevated CA125 at baseline CR was def with 2 CA125 values below ULN observed on 2 consecutive assessmts drawn at least 1 wk apart A pt was considered to have a best overall resp of:CR:if CR as per RECIST \& CA125 /-PR: if CR as per RECIST \& PR as per CA125 OR CR as per RECIST and SD as per CA125 with elevated CA125 at baseline OR PR as per RECIST \& CR/PR or SD as per CA125
Outcome measures
| Measure |
AMG 479
n=61 Participants
AMG 479 administered on day 1 of each 21-day cycle up to disease progression, unacceptable toxicity, withdrawal of consent or sponsor decision to stop the study.
AMG 479: Solution for infusion - 18 mg/kg on day 1 of each 21-day cycle
|
|---|---|
|
Objective Response Rate (ORR) Independent Radiology Committee % of Patients in the Group Who Achieve a Complete or Partial Response According to RECIST Criteria and GCIG CA 125 Response Criteria.
|
1.6 percentage of patients
Interval 0.0 to 8.8
|
SECONDARY outcome
Timeframe: Every 9 (+/- 1 ) weeks during study treatment until documentation of progression or end of study treatment + confirmation PR or CR no less than 4 weeks after initial documentation of responsePopulation: Intent To Treat
Interval from the date of registration to the date of disease progression Investigator assessment As per RECIST (v1.0), disease progression represented an increase of at least 20% in the sum of the longest diameter (SLD) of target lesions, taking as reference the smallest SLD recorded since the treatment started or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Outcome measures
| Measure |
AMG 479
n=61 Participants
AMG 479 administered on day 1 of each 21-day cycle up to disease progression, unacceptable toxicity, withdrawal of consent or sponsor decision to stop the study.
AMG 479: Solution for infusion - 18 mg/kg on day 1 of each 21-day cycle
|
|---|---|
|
Time To Progression (TTP) Investigator Assessment
|
2.037 months
Interval 1.906 to 2.168
|
SECONDARY outcome
Timeframe: At 16 weeks from registrationPopulation: Intent To Treat
RECIST(v1.0): * CR:disappearance of all target les°\&non-target les°\&normalization of tumor marker level * PR:at least 30% decrease in the sum of the LD of target les°-ref the baseline sum LD OR CR for target les°\&incomplete resp/SD for non target les° * SD:insufficient shrinkage for PR or increase for PD-ref the smallest sum LD since ttmt started or Persistence of one/more non-target les°or/\&maintenance of tumor marker level above the normal CA125 level: * PR:elev of CA125 at baseline PR if a ≥ 50% decrease compared to baseline value observed on 2 consec assessmts drawn at least 1 wk apart * CR:elev of CA125 at baseline CR 2 CA125 below ULN observed on 2 consec assessmts drawn at least 1 wk apart * SD:neither CR/PR nor PD Best overall resp of : * CR:if CR per RECIST \& per CA125 * PR:if CR per RECIST \& PR per CA125 OR CR per RECIST and SD per CA125 with elev CA125 at baseline OR PR per RECIST \& CR/PR or SD per CA125 * SD:other cases not qualifying for progression-at least 24 wks
Outcome measures
| Measure |
AMG 479
n=61 Participants
AMG 479 administered on day 1 of each 21-day cycle up to disease progression, unacceptable toxicity, withdrawal of consent or sponsor decision to stop the study.
AMG 479: Solution for infusion - 18 mg/kg on day 1 of each 21-day cycle
|
|---|---|
|
Clinical Benefit Rate (CBR) Investigator Assessmt % of Patients in the gp Who Achieve a Complete Response-CR,Partial Response-PR or Stable Disease-SD for 16wks From Registrat° Considering the Global Response Combining RECIST Criteria and CA125 Assessmts
|
1.7 percentage of patients
Interval 0.0 to 8.9
|
SECONDARY outcome
Timeframe: Day 1 of each cycle during study treatment + follow-up every 6 months for the first 3 years in the study or until death whichever occurs firstPopulation: Intent To Treat
Interval between the date of registration and the date of death
Outcome measures
| Measure |
AMG 479
n=61 Participants
AMG 479 administered on day 1 of each 21-day cycle up to disease progression, unacceptable toxicity, withdrawal of consent or sponsor decision to stop the study.
AMG 479: Solution for infusion - 18 mg/kg on day 1 of each 21-day cycle
|
|---|---|
|
Overall Survival (OS) Investigator Assessment
|
20.994 months
Interval 19.45 to
The mean survival time and its standard error were underestimated because the largest observation was censored and the estimation was restricted to the largest event time.
|
SECONDARY outcome
Timeframe: Day 1 of each cyclePopulation: Intent To Treat
The GCIG criteria (November 2005) were used to define progressive disease, based on serum CA 125 levels, as follows: * Patients with elevated CA 125 pretreatment and normalization of CA 125 needed to show evidence of CA 125 greater than, or equal to, two times the ULN on two occasions at least 1 week apart or * Patients with elevated CA 125 pretreatment, which never normalizes needed to show evidence of CA 125 greater than, or equal to, two times the nadir value on two occasions at least 1 week apart or * Patients with CA 125 in the normal range pretreatment needed to show evidence of CA 125 greater than, or equal to, two times the ULN on two occasions at least 1 week apart.
Outcome measures
| Measure |
AMG 479
n=61 Participants
AMG 479 administered on day 1 of each 21-day cycle up to disease progression, unacceptable toxicity, withdrawal of consent or sponsor decision to stop the study.
AMG 479: Solution for infusion - 18 mg/kg on day 1 of each 21-day cycle
|
|---|---|
|
Time To Marker Progression (TTMP) Investigator Assessment - Interval Form the Date of Registration to the Date of Disease Progression as Per GCIG 2005 Definition of CA 125 Progression.
|
4.961 months
Interval 2.76 to 12.813
|
SECONDARY outcome
Timeframe: Every 9 (+/- 1 ) weeks during study treatment until documentation of progression or end of study treatment + confirmation PR or CR no less than 4 weeks after initial documentation of responsePopulation: Intent To Treat
A patient may have been declared to have progressive disease on the basis of radiological measuremt of tumor lesions assessmt or CA125 evaluation (tumor measuremts taking precedence).Radiological progression was defined as per the RECIST guidelines (Therasse et al, JNCI2000) as at least 20% increase in the sum of the longest diameters of target lesions(ref the smallest sum of the longest diam recorded since the treatmt started or since the appearance of at least 1 new lesion).Serum CA125 progression was defined, according to the 2005 GCIG def: pts with: * Elevated CA125 pretreatmt and normalization of CA125 has to show evidence of CA125≥ 2 times the upper normal limit on 2 occasions at least 1 wk apart OR * Elevated CA125 pretreatmt which never normalized must show evidence of CA125≥ 2 times the nadir value on 2 occasions at least 1 wk apart OR * CA125 in the normal range pretreatmt had to show evidence of CA125 ≥ 2 times the upper normal limit on 2 occasions at least 1 wk apart
Outcome measures
| Measure |
AMG 479
n=61 Participants
AMG 479 administered on day 1 of each 21-day cycle up to disease progression, unacceptable toxicity, withdrawal of consent or sponsor decision to stop the study.
AMG 479: Solution for infusion - 18 mg/kg on day 1 of each 21-day cycle
|
|---|---|
|
Progression-free Survival (PFS) Investigator Assessment - Interval From Registration to Disease Progression or Death Due to Any Cause - According to RECIST and CA 125
|
1.938 months
Interval 1.446 to 2.103
|
Adverse Events
AMG 479
Serious adverse events
| Measure |
AMG 479
n=61 participants at risk
AMG 479 administered on day 1 of each 21-day cycle up to disease progression, unacceptable toxicity, withdrawal of consent or sponsor decision to stop the study.
AMG 479: Solution for infusion - 18 mg/kg on day 1 of each 21-day cycle
|
|---|---|
|
Cardiac disorders
Cardiac Failure Congestive
|
1.6%
1/61 • Number of events 1
|
|
Ear and labyrinth disorders
Deafness
|
1.6%
1/61 • Number of events 1
|
|
Gastrointestinal disorders
Intestinal obstruction
|
3.3%
2/61 • Number of events 2
|
|
Gastrointestinal disorders
Vomiting
|
1.6%
1/61 • Number of events 1
|
|
Infections and infestations
Candida Infection
|
1.6%
1/61 • Number of events 1
|
|
Metabolism and nutrition disorders
Dehydration
|
1.6%
1/61 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
1.6%
1/61 • Number of events 1
|
|
Nervous system disorders
Headache
|
1.6%
1/61 • Number of events 1
|
|
Renal and urinary disorders
Renal failure acute
|
1.6%
1/61 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
1.6%
1/61 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
1.6%
1/61 • Number of events 1
|
Other adverse events
| Measure |
AMG 479
n=61 participants at risk
AMG 479 administered on day 1 of each 21-day cycle up to disease progression, unacceptable toxicity, withdrawal of consent or sponsor decision to stop the study.
AMG 479: Solution for infusion - 18 mg/kg on day 1 of each 21-day cycle
|
|---|---|
|
Gastrointestinal disorders
Abdominal distension
|
11.5%
7/61 • Number of events 7
|
|
Gastrointestinal disorders
Abdominal pain
|
31.1%
19/61 • Number of events 24
|
|
Gastrointestinal disorders
Abdominal pain upper
|
4.9%
3/61 • Number of events 4
|
|
Gastrointestinal disorders
Constipation
|
24.6%
15/61 • Number of events 16
|
|
Gastrointestinal disorders
Diarrhoea
|
27.9%
17/61 • Number of events 24
|
|
Gastrointestinal disorders
Dry mouth
|
8.2%
5/61 • Number of events 5
|
|
Gastrointestinal disorders
Dyspepsia
|
13.1%
8/61 • Number of events 10
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
6.6%
4/61 • Number of events 5
|
|
Gastrointestinal disorders
Nausea
|
26.2%
16/61 • Number of events 27
|
|
Gastrointestinal disorders
Stomatitis
|
8.2%
5/61 • Number of events 5
|
|
Gastrointestinal disorders
Vomiting
|
14.8%
9/61 • Number of events 13
|
|
General disorders
Asthenia
|
24.6%
15/61 • Number of events 19
|
|
General disorders
Chest pain
|
6.6%
4/61 • Number of events 7
|
|
General disorders
Chills
|
13.1%
8/61 • Number of events 12
|
|
General disorders
Fatigue
|
34.4%
21/61 • Number of events 25
|
|
General disorders
Pyrexia
|
8.2%
5/61 • Number of events 6
|
|
Immune system disorders
Hypersensitivity
|
13.1%
8/61 • Number of events 9
|
|
Infections and infestations
Urinary tract infection
|
8.2%
5/61 • Number of events 5
|
|
Metabolism and nutrition disorders
Decreased appetite
|
11.5%
7/61 • Number of events 7
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
9.8%
6/61 • Number of events 7
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
6.6%
4/61 • Number of events 5
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
9.8%
6/61 • Number of events 10
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
9.8%
6/61 • Number of events 6
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
6.6%
4/61 • Number of events 6
|
|
Nervous system disorders
Dizziness
|
9.8%
6/61 • Number of events 6
|
|
Nervous system disorders
Headache
|
16.4%
10/61 • Number of events 14
|
|
Psychiatric disorders
Anxiety
|
6.6%
4/61 • Number of events 5
|
|
Psychiatric disorders
Depression
|
6.6%
4/61 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
6.6%
4/61 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
8.2%
5/61 • Number of events 5
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
6.6%
4/61 • Number of events 4
|
|
Skin and subcutaneous tissue disorders
Rash
|
9.8%
6/61 • Number of events 6
|
Additional Information
Matthieu Rupin
Translational Research In Oncology (formerly CIRG)
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place