Trial Outcomes & Findings for Birinapant for Advanced Ovarian, Fallopian Tube, and Peritoneal Cancer (NCT NCT01681368)
NCT ID: NCT01681368
Last Updated: 2017-05-30
Results Overview
Per the RECIST criteria, CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10mm. Partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
11 participants
Primary outcome timeframe
6 months
Results posted on
2017-05-30
Participant Flow
Participant milestones
| Measure |
Birinapant for Advanced Ovarian,Fallopian Tube & Peritoneal Ca
single arm
Birinapant (TL32711): 47mg/m\^2 intravenous (IV) on days 1, 8 and 15 of each 28 day cycle
|
|---|---|
|
Overall Study
STARTED
|
11
|
|
Overall Study
COMPLETED
|
9
|
|
Overall Study
NOT COMPLETED
|
2
|
Reasons for withdrawal
| Measure |
Birinapant for Advanced Ovarian,Fallopian Tube & Peritoneal Ca
single arm
Birinapant (TL32711): 47mg/m\^2 intravenous (IV) on days 1, 8 and 15 of each 28 day cycle
|
|---|---|
|
Overall Study
Refused further treatment
|
1
|
|
Overall Study
Refused further follow up
|
1
|
Baseline Characteristics
Birinapant for Advanced Ovarian, Fallopian Tube, and Peritoneal Cancer
Baseline characteristics by cohort
| Measure |
Birinapant for Advanced Ovarian,Fallopian Tube & Peritoneal Ca
n=11 Participants
single arm
Birinapant (TL32711): 47mg/m\^2 intravenous (IV) on days 1, 8 and 15 of each 28 day cycle
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
9 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
2 Participants
n=5 Participants
|
|
Age, Continuous
|
58.87 years
STANDARD_DEVIATION 6 • n=5 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
10 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
9 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
11 participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group (ECOG)
0
|
0 Participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group (ECOG)
1
|
10 Participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group (ECOG)
2
|
1 Participants
n=5 Participants
|
|
Histologic subtype, No.
Serous
|
6 Participants
n=5 Participants
|
|
Histologic subtype, No.
Endometrioid
|
1 Participants
n=5 Participants
|
|
Histologic subtype, No.
Clear cell
|
1 Participants
n=5 Participants
|
|
Histologic subtype, No.
Classified
|
3 Participants
n=5 Participants
|
|
No. of Prior Therapies
≤3
|
1 Participants
n=5 Participants
|
|
No. of Prior Therapies
4-6
|
6 Participants
n=5 Participants
|
|
No. of Prior Therapies
≥7
|
4 Participants
n=5 Participants
|
|
Type of Prior Therapy, No.
Chemotherapy
|
11 participants
n=5 Participants
|
|
Type of Prior Therapy, No.
Biologic
|
6 participants
n=5 Participants
|
|
Type of Prior Therapy, No.
Hormonal
|
5 participants
n=5 Participants
|
|
Type of Prior Therapy, No.
Vaccine
|
1 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 6 monthsPer the RECIST criteria, CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10mm. Partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Outcome measures
| Measure |
Birinapant for Advanced Ovarian,Fallopian Tube & Peritoneal Ca
n=11 Participants
single arm
Birinapant (TL32711): 47mg/m\^2 intravenous (IV) on days 1, 8 and 15 of each 28 day cycle
|
|---|---|
|
Objective Response (Complete Response (CR) or Partial Response (PR) Defined by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Criteria) or Disease Stabilization for Greater Than 6 Months
Complete Response
|
0 participants
|
|
Objective Response (Complete Response (CR) or Partial Response (PR) Defined by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Criteria) or Disease Stabilization for Greater Than 6 Months
Partial Response
|
0 participants
|
SECONDARY outcome
Timeframe: 8 monthsHere is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.
Outcome measures
| Measure |
Birinapant for Advanced Ovarian,Fallopian Tube & Peritoneal Ca
n=11 Participants
single arm
Birinapant (TL32711): 47mg/m\^2 intravenous (IV) on days 1, 8 and 15 of each 28 day cycle
|
|---|---|
|
Number of Participants With Adverse Events
|
11 participants
|
SECONDARY outcome
Timeframe: 30, 60, 120, 180 minutes after administration of first dose of BirinapantMeasurement of the plasma concentration of the Birinapant over time. It is used to characterize drug absorption. The single values were analyzed with liquid chromatography/tandem mass spectrometry via a proprietary methodology (TetraLogic Pharma,Malvern, Pa). The values were grouped and averaged for each of the patients to obtain the mean value for each time point.
Outcome measures
| Measure |
Birinapant for Advanced Ovarian,Fallopian Tube & Peritoneal Ca
n=11 Participants
single arm
Birinapant (TL32711): 47mg/m\^2 intravenous (IV) on days 1, 8 and 15 of each 28 day cycle
|
|---|---|
|
Mean Plasma Concentration-Time Curve of Birinapant
Predose
|
0 ng/mL
Standard Deviation 0
|
|
Mean Plasma Concentration-Time Curve of Birinapant
240 minutes post end of infusion (EOI)
|
85 ng/mL
Standard Deviation 20
|
|
Mean Plasma Concentration-Time Curve of Birinapant
30 minutes post end of infusion (EOI)
|
699 ng/mL
Standard Deviation 157
|
|
Mean Plasma Concentration-Time Curve of Birinapant
60 minutes post end of infusion (EOI)
|
415 ng/mL
Standard Deviation 84
|
|
Mean Plasma Concentration-Time Curve of Birinapant
120 minutes post end of infusion (EOI)
|
202 ng/mL
Standard Deviation 43
|
SECONDARY outcome
Timeframe: Prior to treatment and 12 to 22 hours following Cycle 2 Day 15Population: 4 patients did not have the second paired biopsy due to patient refusal.
Levels of Birinapant were measured in core needle biopsies of tumor that had been frozen at the time of acquisition.
Outcome measures
| Measure |
Birinapant for Advanced Ovarian,Fallopian Tube & Peritoneal Ca
n=7 Participants
single arm
Birinapant (TL32711): 47mg/m\^2 intravenous (IV) on days 1, 8 and 15 of each 28 day cycle
|
|---|---|
|
Birinapant Concentration in Tumor Tissue
|
952 ng/g
Interval 185.0 to 1830.0
|
SECONDARY outcome
Timeframe: 0-24hrVolume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
Outcome measures
| Measure |
Birinapant for Advanced Ovarian,Fallopian Tube & Peritoneal Ca
n=11 Participants
single arm
Birinapant (TL32711): 47mg/m\^2 intravenous (IV) on days 1, 8 and 15 of each 28 day cycle
|
|---|---|
|
Calculated Volume of Distribution of Birinapant at Steady State (Vss) in Tumor Tissue
|
119 L
Interval 80.0 to 183.0
|
SECONDARY outcome
Timeframe: 0-24hrVolume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
Outcome measures
| Measure |
Birinapant for Advanced Ovarian,Fallopian Tube & Peritoneal Ca
n=11 Participants
single arm
Birinapant (TL32711): 47mg/m\^2 intravenous (IV) on days 1, 8 and 15 of each 28 day cycle
|
|---|---|
|
Calculated Volume of Distribution of Birinapant at Steady State (Vss) in Plasma
|
132 L
Standard Deviation 33
|
SECONDARY outcome
Timeframe: 0-6 weeksPopulation: 4 patients refused second biopsy.
Proteins were measured using capillary western blot and ratio was calculated between phosphorylated and total NF-kappaB p65. Core 1 tumor samples and peripheral blood mononuclear cells (PBMCs) from each time point were lysed in T-PER buffer (Thermo Scientific) for protein quantification by an automated capillary electrophoresis immunoassay system (Simple Western). The tumor protein lysate (40-60 ng) or PBMC protein lysate (16-77 ng) was analyzed according to the manufacturer's instructions (ProteinSimple, Santa Clara, Calif).
Outcome measures
| Measure |
Birinapant for Advanced Ovarian,Fallopian Tube & Peritoneal Ca
n=7 Participants
single arm
Birinapant (TL32711): 47mg/m\^2 intravenous (IV) on days 1, 8 and 15 of each 28 day cycle
|
|---|---|
|
Ratio of Phosphorylated NF-kappaB-p65 Protein to Total NF-kappaBp65 Protein in Tumor Biopsy Samples
|
0.2 pixel intensity per ng protein
Interval 0.0 to 0.4
|
SECONDARY outcome
Timeframe: Pre treatment and post treatment of Birinapant, approximately 0-6 weeksPopulation: Only 2 pairs of adequate pre- and post-treatment biopsy samples were available for analysis. The remaining paired samples were inadequate for immunohistochemistry because of necrotic debris in the post-treatment biopsy sample (1 specimen) or contamination with blood (4 specimens).
Tumor biopsies were measured for cleaved caspase 3 and gamma-H2A.X by immunofluorescence microscopy. Fold change was calculated by comparing the post-treatment measurements to the pre-treatment levels.
Outcome measures
| Measure |
Birinapant for Advanced Ovarian,Fallopian Tube & Peritoneal Ca
n=2 Participants
single arm
Birinapant (TL32711): 47mg/m\^2 intravenous (IV) on days 1, 8 and 15 of each 28 day cycle
|
|---|---|
|
Coexpression of Cleaved Caspase 3 and Gamma-H2AX in Fixed Specimens
|
3 Fold over baseline
Interval 2.0 to 4.0
|
SECONDARY outcome
Timeframe: 0-24hrClearance is a quantitative measure of the rate at which a drug substance is removed from the body.
Outcome measures
| Measure |
Birinapant for Advanced Ovarian,Fallopian Tube & Peritoneal Ca
n=11 Participants
single arm
Birinapant (TL32711): 47mg/m\^2 intravenous (IV) on days 1, 8 and 15 of each 28 day cycle
|
|---|---|
|
Total Clearance of Birinapant After Administration
|
67.93091577 L/hr
Interval 45.1843727 to 105.7101965
|
Adverse Events
Birinapant for Advanced Ovarian,Fallopian Tube & Peritoneal Ca
Serious events: 11 serious events
Other events: 11 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Birinapant for Advanced Ovarian,Fallopian Tube & Peritoneal Ca
n=11 participants at risk
single arm
Birinapant (TL32711): 47mg/m\^2 intravenous (IV) on days 1, 8 and 15 of each 28 day cycle
|
|---|---|
|
Skin and subcutaneous tissue disorders
Pain of skin
|
9.1%
1/11 • Number of events 1 • 8 months
|
|
Blood and lymphatic system disorders
Anemia
|
45.5%
5/11 • Number of events 8 • 8 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
9.1%
1/11 • Number of events 1 • 8 months
|
|
Gastrointestinal disorders
Colonic obstruction
|
9.1%
1/11 • Number of events 1 • 8 months
|
|
Gastrointestinal disorders
Constipation
|
18.2%
2/11 • Number of events 2 • 8 months
|
|
Metabolism and nutrition disorders
Dehydration
|
9.1%
1/11 • Number of events 1 • 8 months
|
|
Psychiatric disorders
Depression
|
9.1%
1/11 • Number of events 1 • 8 months
|
|
Gastrointestinal disorders
Diarrhea
|
9.1%
1/11 • Number of events 1 • 8 months
|
|
Eye disorders
Eye disorders - Other, specify (diplopia)
|
9.1%
1/11 • Number of events 1 • 8 months
|
|
Nervous system disorders
Facial nerve disorder
|
9.1%
1/11 • Number of events 1 • 8 months
|
|
General disorders
Fatigue
|
9.1%
1/11 • Number of events 1 • 8 months
|
|
Nervous system disorders
Headache
|
9.1%
1/11 • Number of events 1 • 8 months
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
9.1%
1/11 • Number of events 1 • 8 months
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
9.1%
1/11 • Number of events 1 • 8 months
|
|
Investigations
Lymphocyte count decreased
|
54.5%
6/11 • Number of events 10 • 8 months
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
9.1%
1/11 • Number of events 1 • 8 months
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
9.1%
1/11 • Number of events 1 • 8 months
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
9.1%
1/11 • Number of events 1 • 8 months
|
|
Vascular disorders
Thromboembolic event
|
9.1%
1/11 • Number of events 1 • 8 months
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory infection
|
9.1%
1/11 • Number of events 1 • 8 months
|
|
Renal and urinary disorders
Urinary retention
|
9.1%
1/11 • Number of events 2 • 8 months
|
|
Infections and infestations
Urinary tract infection
|
9.1%
1/11 • Number of events 1 • 8 months
|
|
Gastrointestinal disorders
Vomiting
|
18.2%
2/11 • Number of events 2 • 8 months
|
Other adverse events
| Measure |
Birinapant for Advanced Ovarian,Fallopian Tube & Peritoneal Ca
n=11 participants at risk
single arm
Birinapant (TL32711): 47mg/m\^2 intravenous (IV) on days 1, 8 and 15 of each 28 day cycle
|
|---|---|
|
Investigations
Activated partial thromboplastin time prolonged
|
9.1%
1/11 • Number of events 1 • 8 months
|
|
Investigations
Alanine aminotransferase increased
|
36.4%
4/11 • Number of events 4 • 8 months
|
|
Investigations
Alkaline phosphatase increased
|
9.1%
1/11 • Number of events 1 • 8 months
|
|
Immune system disorders
Allergic reaction
|
9.1%
1/11 • Number of events 1 • 8 months
|
|
Blood and lymphatic system disorders
Anemia
|
63.6%
7/11 • Number of events 10 • 8 months
|
|
Metabolism and nutrition disorders
Anorexia
|
27.3%
3/11 • Number of events 3 • 8 months
|
|
Psychiatric disorders
Anxiety
|
9.1%
1/11 • Number of events 1 • 8 months
|
|
Investigations
Aspartate aminotransferase increased
|
18.2%
2/11 • Number of events 2 • 8 months
|
|
General disorders
Chills
|
9.1%
1/11 • Number of events 1 • 8 months
|
|
Gastrointestinal disorders
Constipation
|
9.1%
1/11 • Number of events 1 • 8 months
|
|
Investigations
Creatinine increased
|
27.3%
3/11 • Number of events 4 • 8 months
|
|
Gastrointestinal disorders
Diarrhea
|
45.5%
5/11 • Number of events 7 • 8 months
|
|
Nervous system disorders
Dizziness
|
9.1%
1/11 • Number of events 1 • 8 months
|
|
General disorders
Edema limbs
|
9.1%
1/11 • Number of events 1 • 8 months
|
|
General disorders
Edema trunk
|
9.1%
1/11 • Number of events 1 • 8 months
|
|
General disorders
Fatigue
|
45.5%
5/11 • Number of events 5 • 8 months
|
|
General disorders
Fever
|
9.1%
1/11 • Number of events 1 • 8 months
|
|
Nervous system disorders
Headache
|
27.3%
3/11 • Number of events 3 • 8 months
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
18.2%
2/11 • Number of events 3 • 8 months
|
|
Metabolism and nutrition disorders
Hypernatremia
|
9.1%
1/11 • Number of events 1 • 8 months
|
|
Metabolism and nutrition disorders
Hyperuricemia
|
18.2%
2/11 • Number of events 2 • 8 months
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
63.6%
7/11 • Number of events 10 • 8 months
|
|
Metabolism and nutrition disorders
Hypokalemia
|
18.2%
2/11 • Number of events 3 • 8 months
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
27.3%
3/11 • Number of events 4 • 8 months
|
|
Metabolism and nutrition disorders
Hyponatremia
|
18.2%
2/11 • Number of events 2 • 8 months
|
|
Investigations
Lipase increased
|
9.1%
1/11 • Number of events 1 • 8 months
|
|
Investigations
Lymphocyte count decreased
|
36.4%
4/11 • Number of events 7 • 8 months
|
|
Metabolism and nutrition disorders
Metabolism and nutrition disorders - Other, specify (low protein)
|
9.1%
1/11 • Number of events 1 • 8 months
|
|
Gastrointestinal disorders
Nausea
|
36.4%
4/11 • Number of events 6 • 8 months
|
|
Investigations
Platelet count decreased
|
18.2%
2/11 • Number of events 3 • 8 months
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
18.2%
2/11 • Number of events 2 • 8 months
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
9.1%
1/11 • Number of events 1 • 8 months
|
|
Investigations
Serum amylase increased
|
27.3%
3/11 • Number of events 4 • 8 months
|
|
Reproductive system and breast disorders
Vaginal hemorrhage
|
9.1%
1/11 • Number of events 1 • 8 months
|
|
Gastrointestinal disorders
Vomiting
|
18.2%
2/11 • Number of events 2 • 8 months
|
|
Investigations
Weight loss
|
18.2%
2/11 • Number of events 2 • 8 months
|
|
Investigations
White blood cell decreased
|
18.2%
2/11 • Number of events 2 • 8 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place