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Birinapant for Advanced Ovarian, Fallopian Tube, and Peritoneal Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01681368
Recruitment Status : Terminated (Accrual was terminated for lack of a clinical benefit.)
First Posted : September 7, 2012
Results First Posted : February 3, 2015
Last Update Posted : May 30, 2017
Sponsor:
Information provided by (Responsible Party):
Christina Annunziata, M.D., National Institutes of Health Clinical Center (CC)

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Epithelial Ovarian Cancer
Peritoneal Neoplasms
Fallopian Tube Neoplasms
Intervention Drug: Birinapant (TL32711)
Enrollment 11
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Birinapant for Advanced Ovarian,Fallopian Tube & Peritoneal Ca
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single arm

Birinapant (TL32711): 47mg/m^2 intravenous (IV) on days 1, 8 and 15 of each 28 day cycle

Period Title: Overall Study
Started 11
Completed 9
Not Completed 2
Reason Not Completed
Refused further treatment             1
Refused further follow up             1
Arm/Group Title Birinapant for Advanced Ovarian,Fallopian Tube & Peritoneal Ca
Hide Arm/Group Description

single arm

Birinapant (TL32711): 47mg/m^2 intravenous (IV) on days 1, 8 and 15 of each 28 day cycle

Overall Number of Baseline Participants 11
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants
<=18 years
0
   0.0%
Between 18 and 65 years
9
  81.8%
>=65 years
2
  18.2%
Age, Continuous  
Median (Standard Deviation)
Unit of measure:  Years
Number Analyzed 11 participants
58.87  (6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants
Female
11
 100.0%
Male
0
   0.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants
Hispanic or Latino
0
   0.0%
Not Hispanic or Latino
10
  90.9%
Unknown or Not Reported
1
   9.1%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
1
   9.1%
White
9
  81.8%
More than one race
0
   0.0%
Unknown or Not Reported
1
   9.1%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 11 participants
11
Eastern Cooperative Oncology Group (ECOG)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants
0
0
   0.0%
1
10
  90.9%
2
1
   9.1%
[1]
Measure Description: ECOG: 0 (Normal activity. Fully active, able to carry on all pre-disease performance without restriction.), 1 (Symptoms, but ambulatory. Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature (e.g., light housework, office work), and 2 (In bed <50% of the time. Ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hour.).
Histologic subtype, No.  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants
Serous
6
  54.5%
Endometrioid
1
   9.1%
Clear cell
1
   9.1%
Classified
3
  27.3%
No. of Prior Therapies  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants
≤3
1
   9.1%
4-6
6
  54.5%
≥7
4
  36.4%
Type of Prior Therapy, No.  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 11 participants
Chemotherapy 11
Biologic 6
Hormonal 5
Vaccine 1
1.Primary Outcome
Title 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
Hide Description 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.
Time Frame 6 months
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[Not Specified]
Arm/Group Title Birinapant for Advanced Ovarian,Fallopian Tube & Peritoneal Ca
Hide Arm/Group Description:

single arm

Birinapant (TL32711): 47mg/m^2 intravenous (IV) on days 1, 8 and 15 of each 28 day cycle

Overall Number of Participants Analyzed 11
Measure Type: Number
Unit of Measure: participants
Complete Response 0
Partial Response 0
2.Secondary Outcome
Title Number of Participants With Adverse Events
Hide Description Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.
Time Frame 8 months
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Hide Analysis Population Description
[Not Specified]
Arm/Group Title Birinapant for Advanced Ovarian,Fallopian Tube & Peritoneal Ca
Hide Arm/Group Description:

single arm

Birinapant (TL32711): 47mg/m^2 intravenous (IV) on days 1, 8 and 15 of each 28 day cycle

Overall Number of Participants Analyzed 11
Measure Type: Number
Unit of Measure: participants
11
3.Secondary Outcome
Title Mean Plasma Concentration-Time Curve of Birinapant
Hide Description Measurement 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.
Time Frame 30, 60, 120, 180 minutes after administration of first dose of Birinapant
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Hide Analysis Population Description
[Not Specified]
Arm/Group Title Birinapant for Advanced Ovarian,Fallopian Tube & Peritoneal Ca
Hide Arm/Group Description:

single arm

Birinapant (TL32711): 47mg/m^2 intravenous (IV) on days 1, 8 and 15 of each 28 day cycle

Overall Number of Participants Analyzed 11
Mean (Standard Deviation)
Unit of Measure: ng/mL
Predose 0  (0)
30 minutes post end of infusion (EOI) 699  (157)
60 minutes post end of infusion (EOI) 415  (84)
120 minutes post end of infusion (EOI) 202  (43)
240 minutes post end of infusion (EOI) 85  (20)
4.Secondary Outcome
Title Birinapant Concentration in Tumor Tissue
Hide Description Levels of Birinapant were measured in core needle biopsies of tumor that had been frozen at the time of acquisition.
Time Frame Prior to treatment and 12 to 22 hours following Cycle 2 Day 15
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Hide Analysis Population Description
4 patients did not have the second paired biopsy due to patient refusal.
Arm/Group Title Birinapant for Advanced Ovarian,Fallopian Tube & Peritoneal Ca
Hide Arm/Group Description:

single arm

Birinapant (TL32711): 47mg/m^2 intravenous (IV) on days 1, 8 and 15 of each 28 day cycle

Overall Number of Participants Analyzed 7
Mean (Full Range)
Unit of Measure: ng/g
952
(185 to 1830)
5.Secondary Outcome
Title Calculated Volume of Distribution of Birinapant at Steady State (Vss) in Tumor Tissue
Hide Description Volume 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.
Time Frame 0-24hr
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Hide Analysis Population Description
[Not Specified]
Arm/Group Title Birinapant for Advanced Ovarian,Fallopian Tube & Peritoneal Ca
Hide Arm/Group Description:

single arm

Birinapant (TL32711): 47mg/m^2 intravenous (IV) on days 1, 8 and 15 of each 28 day cycle

Overall Number of Participants Analyzed 11
Mean (Full Range)
Unit of Measure: L
119
(80 to 183)
6.Secondary Outcome
Title Calculated Volume of Distribution of Birinapant at Steady State (Vss) in Plasma
Hide Description Volume 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.
Time Frame 0-24hr
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Birinapant for Advanced Ovarian,Fallopian Tube & Peritoneal Ca
Hide Arm/Group Description:

single arm

Birinapant (TL32711): 47mg/m^2 intravenous (IV) on days 1, 8 and 15 of each 28 day cycle

Overall Number of Participants Analyzed 11
Mean (Standard Deviation)
Unit of Measure: L
132  (33)
7.Secondary Outcome
Title Ratio of Phosphorylated NF-kappaB-p65 Protein to Total NF-kappaBp65 Protein in Tumor Biopsy Samples
Hide Description 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).
Time Frame 0-6 weeks
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Hide Analysis Population Description
4 patients refused second biopsy.
Arm/Group Title Birinapant for Advanced Ovarian,Fallopian Tube & Peritoneal Ca
Hide Arm/Group Description:

single arm

Birinapant (TL32711): 47mg/m^2 intravenous (IV) on days 1, 8 and 15 of each 28 day cycle

Overall Number of Participants Analyzed 7
Mean (Full Range)
Unit of Measure: pixel intensity per ng protein
0.2
(0 to 0.4)
8.Secondary Outcome
Title Coexpression of Cleaved Caspase 3 and Gamma-H2AX in Fixed Specimens
Hide Description 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.
Time Frame Pre treatment and post treatment of Birinapant, approximately 0-6 weeks
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Hide Analysis Population Description
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).
Arm/Group Title Birinapant for Advanced Ovarian,Fallopian Tube & Peritoneal Ca
Hide Arm/Group Description:

single arm

Birinapant (TL32711): 47mg/m^2 intravenous (IV) on days 1, 8 and 15 of each 28 day cycle

Overall Number of Participants Analyzed 2
Median (Full Range)
Unit of Measure: Fold over baseline
3
(2 to 4)
9.Secondary Outcome
Title Total Clearance of Birinapant After Administration
Hide Description Clearance is a quantitative measure of the rate at which a drug substance is removed from the body.
Time Frame 0-24hr
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Hide Analysis Population Description
[Not Specified]
Arm/Group Title Birinapant for Advanced Ovarian,Fallopian Tube & Peritoneal Ca
Hide Arm/Group Description:

single arm

Birinapant (TL32711): 47mg/m^2 intravenous (IV) on days 1, 8 and 15 of each 28 day cycle

Overall Number of Participants Analyzed 11
Mean (Full Range)
Unit of Measure: L/hr
67.93091577
(45.1843727 to 105.7101965)
Time Frame 8 months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Birinapant for Advanced Ovarian,Fallopian Tube & Peritoneal Ca
Hide Arm/Group Description

single arm

Birinapant (TL32711): 47mg/m^2 intravenous (IV) on days 1, 8 and 15 of each 28 day cycle

All-Cause Mortality
Birinapant for Advanced Ovarian,Fallopian Tube & Peritoneal Ca
Affected / at Risk (%)
Total   0/11 (0.00%)    
Hide Serious Adverse Events
Birinapant for Advanced Ovarian,Fallopian Tube & Peritoneal Ca
Affected / at Risk (%) # Events
Total   11/11 (100.00%)    
Blood and lymphatic system disorders   
Anemia  1  5/11 (45.45%)  8
Eye disorders   
Eye disorders - Other, specify (diplopia)  1  1/11 (9.09%)  1
Gastrointestinal disorders   
Colonic obstruction  1  1/11 (9.09%)  1
Constipation  1  2/11 (18.18%)  2
Diarrhea  1  1/11 (9.09%)  1
Small intestinal obstruction  1  1/11 (9.09%)  1
Vomiting  1  2/11 (18.18%)  2
General disorders   
Fatigue  1  1/11 (9.09%)  1
Infections and infestations   
Urinary tract infection  1  1/11 (9.09%)  1
Investigations   
Lymphocyte count decreased  1  6/11 (54.55%)  10
Metabolism and nutrition disorders   
Dehydration  1  1/11 (9.09%)  1
Hypercalcemia  1  1/11 (9.09%)  1
Hypoalbuminemia  1  1/11 (9.09%)  1
Musculoskeletal and connective tissue disorders   
Back pain  1  1/11 (9.09%)  1
Pain in extremity  1  1/11 (9.09%)  1
Nervous system disorders   
Facial nerve disorder  1  1/11 (9.09%)  1
Headache  1  1/11 (9.09%)  1
Psychiatric disorders   
Depression  1  1/11 (9.09%)  1
Renal and urinary disorders   
Urinary retention  1  1/11 (9.09%)  2
Respiratory, thoracic and mediastinal disorders   
Pleural effusion  1  1/11 (9.09%)  1
Upper respiratory infection  1  1/11 (9.09%)  1
Skin and subcutaneous tissue disorders   
Pain of skin  1  1/11 (9.09%)  1
Vascular disorders   
Thromboembolic event  1  1/11 (9.09%)  1
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Birinapant for Advanced Ovarian,Fallopian Tube & Peritoneal Ca
Affected / at Risk (%) # Events
Total   11/11 (100.00%)    
Blood and lymphatic system disorders   
Anemia  1  7/11 (63.64%)  10
Gastrointestinal disorders   
Constipation  1  1/11 (9.09%)  1
Diarrhea  1  5/11 (45.45%)  7
Nausea  1  4/11 (36.36%)  6
Vomiting  1  2/11 (18.18%)  2
General disorders   
Chills  1  1/11 (9.09%)  1
Edema limbs  1  1/11 (9.09%)  1
Edema trunk  1  1/11 (9.09%)  1
Fatigue  1  5/11 (45.45%)  5
Fever  1  1/11 (9.09%)  1
Immune system disorders   
Allergic reaction  1  1/11 (9.09%)  1
Investigations   
Activated partial thromboplastin time prolonged  1  1/11 (9.09%)  1
Alanine aminotransferase increased  1  4/11 (36.36%)  4
Alkaline phosphatase increased  1  1/11 (9.09%)  1
Aspartate aminotransferase increased  1  2/11 (18.18%)  2
Creatinine increased  1  3/11 (27.27%)  4
Lipase increased  1  1/11 (9.09%)  1
Lymphocyte count decreased  1  4/11 (36.36%)  7
Platelet count decreased  1  2/11 (18.18%)  3
Serum amylase increased  1  3/11 (27.27%)  4
Weight loss  1  2/11 (18.18%)  2
White blood cell decreased  1  2/11 (18.18%)  2
Metabolism and nutrition disorders   
Anorexia  1  3/11 (27.27%)  3
Hypercalcemia  1  2/11 (18.18%)  3
Hypernatremia  1  1/11 (9.09%)  1
Hyperuricemia  1  2/11 (18.18%)  2
Hypoalbuminemia  1  7/11 (63.64%)  10
Hypokalemia  1  2/11 (18.18%)  3
Hypomagnesemia  1  3/11 (27.27%)  4
Hyponatremia  1  2/11 (18.18%)  2
Metabolism and nutrition disorders - Other, specify (low protein)  1  1/11 (9.09%)  1
Nervous system disorders   
Dizziness  1  1/11 (9.09%)  1
Headache  1  3/11 (27.27%)  3
Psychiatric disorders   
Anxiety  1  1/11 (9.09%)  1
Reproductive system and breast disorders   
Vaginal hemorrhage  1  1/11 (9.09%)  1
Skin and subcutaneous tissue disorders   
Rash acneiform  1  2/11 (18.18%)  2
Rash maculo-papular  1  1/11 (9.09%)  1
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Christina Annunziata
Organization: National Cancer Institute
Phone: 301-402-7189
EMail: annunzic@mail.nih.gov
Layout table for additonal information
Responsible Party: Christina Annunziata, M.D., National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier: NCT01681368    
Other Study ID Numbers: 120191
12-C-0191
First Submitted: September 5, 2012
First Posted: September 7, 2012
Results First Submitted: January 21, 2015
Results First Posted: February 3, 2015
Last Update Posted: May 30, 2017