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Pilot Trial of BMN 673, an Oral PARP Inhibitor, in Patients With Advanced Solid Tumors and Deleterious BRCA Mutations

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ClinicalTrials.gov Identifier: NCT01989546
Recruitment Status : Completed
First Posted : November 21, 2013
Results First Posted : January 27, 2021
Last Update Posted : February 23, 2021
Sponsor:
Information provided by (Responsible Party):
Alice Chen, M.D., National Cancer Institute (NCI)

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Advanced Ovarian Cancer
Primary Peritoneal Cancer
Advanced Breast Cancer
Advanced Solid Tumors
Intervention Drug: BMN 673
Enrollment 9
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Talazoparib (BMN 673)
Hide Arm/Group Description Single-agent BMN 673 (talazoparib) dosed orally at 1 mg/day in 28-day cycles. This poly (ADP-ribose) polymerase (PARP) inhibitor has been shown to cause single-agent synthetic lethality in breast cancer 1 and breast cancer 2 (BRCA1/2)- and phosphatase and tensin homolog (PTEN)-deficient cell lines, and has potent antitumor activity in animal models of tumors harboring mutations in deoxyribonucleic acid (DNA) repair pathways.
Period Title: Overall Study
Started 9
Completed 0
Not Completed 9
Reason Not Completed
Clinical Progression             1
Disease progression on study             8
Arm/Group Title Talazoparib (BMN 673)
Hide Arm/Group Description Single-agent BMN 673 (talazoparib) dosed orally at 1 mg/day in 28-day cycles. This poly (ADP-ribose) polymerase (PARP) inhibitor has been shown to cause single-agent synthetic lethality in breast cancer 1 and breast cancer 2 (BRCA1/2)- and phosphatase and tensin homolog (PTEN)-deficient cell lines, and has potent antitumor activity in animal models of tumors harboring mutations in deoxyribonucleic acid (DNA) repair pathways.
Overall Number of Baseline Participants 9
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants
<=18 years
0
   0.0%
Between 18 and 65 years
5
  55.6%
>=65 years
4
  44.4%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 9 participants
61.23  (12.33)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants
Female
5
  55.6%
Male
4
  44.4%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants
Hispanic or Latino
0
   0.0%
Not Hispanic or Latino
9
 100.0%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 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
  11.1%
White
8
  88.9%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 9 participants
9
1.Primary Outcome
Title Percent of Participants Who Achieve a Sustained Progressive Disease (PD) Response, Defined to be at Least 4% Nuclear Area Positive (NAP) γH2AX at the Day 8 Biopsy
Hide Description Evaluation of drug effect on deoxyribonuclecic acid (DNA) damage response will be performed using immunofluorescence assays to measure the DNA damage repair marker γH2A (the phosphorylated form of histone family member X, H2AX) in the nucleus of tumor cells obtained via core biopsy.
Time Frame Cycle 1, day 8
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Talazoparib (BMN 673)
Hide Arm/Group Description:
Single-agent BMN 673 (talazoparib) dosed orally at 1 mg/day in 28-day cycles. This poly (ADP-ribose) polymerase (PARP) inhibitor has been shown to cause single-agent synthetic lethality in breast cancer 1 and breast cancer 2 (BRCA1/2)- and phosphatase and tensin homolog (PTEN)-deficient cell lines, and has potent antitumor activity in animal models of tumors harboring mutations in deoxyribonucleic acid (DNA) repair pathways.
Overall Number of Participants Analyzed 9
Measure Type: Number
Unit of Measure: percentage of participants
44.4
2.Secondary Outcome
Title Response Rate (Complete Response (CR) + Partial Response (PR) of Treatment With Talazoparib (BMN 673) in Participants With Deleterious Breast Cancer (BRCA) Mutations
Hide Description Response will be evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST)1. 1 guidelines; restaging scans will be carried out every 2 cycles. Complete Response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to <10 mm. Partial Response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. And progression is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The appearance of one or more new lesions is also considered progressions.
Time Frame Restaging scans will be carried out every 2 cycles (8 weeks) until the end of treatment (average, 7 months)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Talazoparib (BMN 673)
Hide Arm/Group Description:
Single-agent BMN 673 (talazoparib) dosed orally at 1 mg/day in 28-day cycles. This poly (ADP-ribose) polymerase (PARP) inhibitor has been shown to cause single-agent synthetic lethality in breast cancer 1 and breast cancer 2 (BRCA1/2)- and phosphatase and tensin homolog (PTEN)-deficient cell lines, and has potent antitumor activity in animal models of tumors harboring mutations in deoxyribonucleic acid (DNA) repair pathways.
Overall Number of Participants Analyzed 9
Measure Type: Count of Participants
Unit of Measure: Participants
Complete Response
0
   0.0%
Partial Response
5
  55.6%
3.Other Pre-specified Outcome
Title Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)
Hide Description Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Time Frame Date treatment consent signed to date off study, approximately 28 months and 24 days.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Talazoparib (BMN 673)
Hide Arm/Group Description:
Single-agent BMN 673 (talazoparib) dosed orally at 1 mg/day in 28-day cycles. This poly (ADP-ribose) polymerase (PARP) inhibitor has been shown to cause single-agent synthetic lethality in breast cancer 1 and breast cancer 2 (BRCA1/2)- and phosphatase and tensin homolog (PTEN)-deficient cell lines, and has potent antitumor activity in animal models of tumors harboring mutations in deoxyribonucleic acid (DNA) repair pathways.
Overall Number of Participants Analyzed 9
Measure Type: Count of Participants
Unit of Measure: Participants
9
 100.0%
Time Frame Date treatment consent signed to date off study, approximately 28 months and 24 days.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Talazoparib (BMN 673)
Hide Arm/Group Description Single-agent BMN 673 (talazoparib) dosed orally at 1 mg/day in 28-day cycles. This poly (ADP-ribose) polymerase (PARP) inhibitor has been shown to cause single-agent synthetic lethality in breast cancer 1 and breast cancer 2 (BRCA1/2)- and phosphatase and tensin homolog (PTEN)-deficient cell lines, and has potent antitumor activity in animal models of tumors harboring mutations in deoxyribonucleic acid (DNA) repair pathways.
All-Cause Mortality
Talazoparib (BMN 673)
Affected / at Risk (%)
Total   0/9 (0.00%)    
Hide Serious Adverse Events
Talazoparib (BMN 673)
Affected / at Risk (%) # Events
Total   3/9 (33.33%)    
Blood and lymphatic system disorders   
Anemia  1  3/9 (33.33%)  3
Investigations   
Platelet count decreased  1  1/9 (11.11%)  2
Metabolism and nutrition disorders   
Hypocalcemia  1  1/9 (11.11%)  1
Hypokalemia  1  1/9 (11.11%)  1
1
Term from vocabulary, CTCAE (5.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Talazoparib (BMN 673)
Affected / at Risk (%) # Events
Total   9/9 (100.00%)    
Blood and lymphatic system disorders   
Anemia  1  6/9 (66.67%)  33
Cardiac disorders   
Palpitations  1  2/9 (22.22%)  2
Ventricular arrhythmia  1  1/9 (11.11%)  1
Ear and labyrinth disorders   
Tinnitus  1  1/9 (11.11%)  3
Eye disorders   
Eye disorders - Other, Eye disorder; let eye itching  1  1/9 (11.11%)  1
Gastrointestinal disorders   
Abdominal pain  1  3/9 (33.33%)  4
Bloating  1  1/9 (11.11%)  1
Diarrhea  1  5/9 (55.56%)  11
Dyspepsia  1  1/9 (11.11%)  1
Nausea  1  7/9 (77.78%)  10
Oral pain  1  1/9 (11.11%)  1
Vomiting  1  4/9 (44.44%)  5
General disorders   
Chills  1  1/9 (11.11%)  1
Edema limbs  1  1/9 (11.11%)  1
Fatigue  1  4/9 (44.44%)  5
Fever  1  1/9 (11.11%)  1
Flu like symptoms  1  2/9 (22.22%)  4
Pain  1  2/9 (22.22%)  4
Infections and infestations   
Upper respiratory infection  1  2/9 (22.22%)  2
Urinary tract infection  1  1/9 (11.11%)  1
Investigations   
Activated partial thromboplastin time prolonged  1  4/9 (44.44%)  5
Alanine aminotransferase increased  1  3/9 (33.33%)  3
Alkaline phosphatase increased  1  2/9 (22.22%)  4
Aspartate aminotransferase increased  1  3/9 (33.33%)  3
Creatinine increased  1  2/9 (22.22%)  2
Lymphocyte count decreased  1  8/9 (88.89%)  32
Neutrophil count decreased  1  6/9 (66.67%)  22
Platelet count decreased  1  8/9 (88.89%)  19
Weight loss  1  3/9 (33.33%)  5
White blood cell decreased  1  8/9 (88.89%)  38
Metabolism and nutrition disorders   
Anorexia  1  3/9 (33.33%)  3
Hyperglycemia  1  1/9 (11.11%)  1
Hyperkalemia  1  1/9 (11.11%)  1
Hypernatremia  1  2/9 (22.22%)  2
Hypoalbuminemia  1  4/9 (44.44%)  6
Hypocalcemia  1  1/9 (11.11%)  2
Hypoglycemia  1  1/9 (11.11%)  1
Hypokalemia  1  2/9 (22.22%)  5
Hypomagnesemia  1  1/9 (11.11%)  3
Hyponatremia  1  1/9 (11.11%)  1
Hypophosphatemia  1  1/9 (11.11%)  1
Musculoskeletal and connective tissue disorders   
Arthralgia  1  1/9 (11.11%)  1
Back pain  1  2/9 (22.22%)  4
Buttock pain  1  1/9 (11.11%)  1
Generalized muscle weakness  1  1/9 (11.11%)  1
Muscle weakness lower limb  1  1/9 (11.11%)  1
Muscle weakness upper limb  1  1/9 (11.11%)  1
Myalgia  1  1/9 (11.11%)  1
Pain in extremity  1  2/9 (22.22%)  3
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Tumor pain  1  1/9 (11.11%)  1
Nervous system disorders   
Dizziness  1  3/9 (33.33%)  8
Extrapyramidal disorder  1  1/9 (11.11%)  1
Headache  1  2/9 (22.22%)  4
Renal and urinary disorders   
Renal calculi  1  1/9 (11.11%)  1
Urinary frequency  1  1/9 (11.11%)  1
Respiratory, thoracic and mediastinal disorders   
Allergic rhinitis  1  2/9 (22.22%)  2
Cough  1  1/9 (11.11%)  1
Dyspnea  1  1/9 (11.11%)  4
Epistaxis  1  1/9 (11.11%)  1
Laryngeal hemorrhage  1  1/9 (11.11%)  2
Laryngeal inflammation  1  1/9 (11.11%)  1
Pleural effusion  1  1/9 (11.11%)  1
Productive cough  1  1/9 (11.11%)  1
Rash acneiform  1  1/9 (11.11%)  2
Sore throat  1  1/9 (11.11%)  1
Skin and subcutaneous tissue disorders   
Erythema multiforme  1  1/9 (11.11%)  1
Surgical and medical procedures   
Surgical and medical procedures - Other, Surgical and medical procedure - Bronchoscopy  1  1/9 (11.11%)  1
Vascular disorders   
Hot flashes  1  1/9 (11.11%)  1
Hypertension  1  3/9 (33.33%)  3
Hypotension  1  2/9 (22.22%)  2
1
Term from vocabulary, CTCAE (5.0)
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. Alice P. Chen
Organization: National Cancer Institute
Phone: 240-781-3274
EMail: chenali@mail.nih.gov
Layout table for additonal information
Responsible Party: Alice Chen, M.D., National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01989546    
Other Study ID Numbers: 140015
14-C-0015
First Submitted: November 16, 2013
First Posted: November 21, 2013
Results First Submitted: January 8, 2021
Results First Posted: January 27, 2021
Last Update Posted: February 23, 2021