Trial Outcomes & Findings for Talazoparib Before Standard Therapy in Treating Patients With Invasive, BRCA-Mutated Breast Cancer (NCT NCT02282345)

Last Updated: 2022-07-06

Results Overview

Pathologic response was documented using the Residual Cancer Burden (RCB) Calculator. Residual cancer burden by ICR will be reported as a categorical variable with four classes (categories) RCB 0 (pCR) which correlates to no invasive disease in breast and lymph, I (minimal RCB), II (moderate RCB), and III (extensive RCB). Up to two fine needle aspirates (FNAs) will also be obtained at each time point for a total of up to 6 FNA's for the trial, which will be used for the patient derived xenograft models. Pre-study biopsies, as well as biopsies within 7 days prior to the completion of 2 months of talazoparib will be collected via diagnostic imaging. During the expansion phase of this trial, ultrasounds will be obtained every 2 cycles (+/- 1 week). Therapy will be discontinued if the Physician or PI indicates clinically significant progression of disease.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

36 participants

Primary outcome timeframe

Up to 6 months

Results posted on

2022-07-06

Participant Flow

All participants were recruited from the breast medical oncology clinic at MD Anderson Cancer Center

36 participants signed the consent, 3 participants were inevaluable

Participant milestones

Participant milestones
Measure	Talazoparib (2 Months) Talazoparib was administered as single-agent oral dose of 1 mg per day for six cycles (each cycle was 28 days) for 2 months followed by standard of care chemotherapy.	Expansion Arm Talazoparib (6 Months) + Surgery Talazoparib will be administered orally at 1 mg per day for at least 4 and up to 6 cycles. Each cycle will consist of 28 days (+/-3 days) followed by surgery or standard of care chemotherapy.
Overall Study STARTED	13	20
Overall Study COMPLETED	13	19
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Talazoparib (2 Months) Talazoparib was administered as single-agent oral dose of 1 mg per day for six cycles (each cycle was 28 days) for 2 months followed by standard of care chemotherapy.	Expansion Arm Talazoparib (6 Months) + Surgery Talazoparib will be administered orally at 1 mg per day for at least 4 and up to 6 cycles. Each cycle will consist of 28 days (+/-3 days) followed by surgery or standard of care chemotherapy.
Overall Study Progression	0	1

Baseline Characteristics

Talazoparib Before Standard Therapy in Treating Patients With Invasive, BRCA-Mutated Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Talazoparib - (2 Months) n=13 Participants Talazoparib was administered as single-agent oral dose of 1 mg per day for six cycles (each cycle was 28 days) for 2 months followed by standard of care chemotherapy.	Expansion Arm (Talazoparib (6 Months) + Surgery) n=20 Participants Talazoparib will be administered orally at 1 mg per day for at least 4 and up to 6 cycles. Each cycle will consist of 28 days (+/-3 days) followed by surgery or standard of care chemotherapy.	Total n=33 Participants Total of all reporting groups
Age, Continuous	40 years n=5 Participants	38 years n=7 Participants	38 years n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants	20 Participants n=7 Participants	33 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=5 Participants	15 Participants n=7 Participants	25 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Region of Enrollment United States	13 participants n=5 Participants	20 participants n=7 Participants	33 participants n=5 Participants
Number of Participants with Breast Cancer Gene and 2 (BRCA1/2) Mutations at Baseline BRCA1	10 Participants n=5 Participants	16 Participants n=7 Participants	26 Participants n=5 Participants
Number of Participants with Breast Cancer Gene and 2 (BRCA1/2) Mutations at Baseline BRCA2	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Clinical stage I	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Clinical stage II	9 Participants n=5 Participants	12 Participants n=7 Participants	21 Participants n=5 Participants
Clinical stage III	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Histology Ductal	12 Participants n=5 Participants	18 Participants n=7 Participants	30 Participants n=5 Participants
Histology Metaplastic	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Histology Metaplastic chondrosarcomatous	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Chemotherapy regimen used AC followed or preceded by weekly taxol	13 Participants n=5 Participants	0 Participants n=7 Participants	13 Participants n=5 Participants
Chemotherapy regimen used Addition of carboplatin to weekly taxol	6 Participants n=5 Participants	0 Participants n=7 Participants	6 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 6 months

Population: 1 patient did not go to surgery but went to chemotherapy for suspected progression

Outcome measures

Outcome measures
Measure	Talazoparib (2 Months) +(SOC) Chemotherapy n=13 Participants Talazoparib was administered as single-agent oral dose of 1 mg per day for six cycles (each cycle was 28 days) for 2 months followed by standard of care (SOC) chemotherapy.	Expansion Arm Talazoparib (6 Months) + Surgery n=20 Participants Talazoparib will be administered orally at 1 mg per day for at least 4 and up to 6 cycles. Each cycle will consist of 28 days (+/-3 days) followed by surgery or standard of care chemotherapy.
Number of Participants With Overall Pathological Complete Response (pCR) Residual Cancer Burden III	0 Participants	2 Participants
Number of Participants With Overall Pathological Complete Response (pCR) Residual Cancer Burden 0	7 Participants	10 Participants
Number of Participants With Overall Pathological Complete Response (pCR) Residual Cancer Burden I	3 Participants	2 Participants
Number of Participants With Overall Pathological Complete Response (pCR) Residual cancer Burden II	3 Participants	5 Participants

PRIMARY outcome

Timeframe: up to 6 months

To assess the toxicity profile of women taking single agent Talazoparib prior to surgery. If greater than 33% of the patients enrolled have either a grade 4 toxicity possibly, probably, or definitely related to the treatment as attributed by the Principal Investigator, or requires a delay in treatment for greater than 4 weeks due to toxicity.

Outcome measures

Outcome measures
Measure	Talazoparib (2 Months) +(SOC) Chemotherapy n=13 Participants Talazoparib was administered as single-agent oral dose of 1 mg per day for six cycles (each cycle was 28 days) for 2 months followed by standard of care (SOC) chemotherapy.	Expansion Arm Talazoparib (6 Months) + Surgery n=20 Participants Talazoparib will be administered orally at 1 mg per day for at least 4 and up to 6 cycles. Each cycle will consist of 28 days (+/-3 days) followed by surgery or standard of care chemotherapy.
Number of Participants With Grade 4 Toxicities	0 Participants	1 Participants

SECONDARY outcome

Timeframe: 2 months

Imaging was the primary measures response with tumor volume shrinkage after 2 months of Talazoparib prior to proceeding with standard chemotherapy for all participants. The clinical response to Talazoparib in the neoadjuvant setting in a pilot trial setting.

Outcome measures

Outcome measures
Measure	Talazoparib (2 Months) +(SOC) Chemotherapy n=13 Participants Talazoparib was administered as single-agent oral dose of 1 mg per day for six cycles (each cycle was 28 days) for 2 months followed by standard of care (SOC) chemotherapy.	Expansion Arm Talazoparib (6 Months) + Surgery Talazoparib will be administered orally at 1 mg per day for at least 4 and up to 6 cycles. Each cycle will consist of 28 days (+/-3 days) followed by surgery or standard of care chemotherapy.
Median Clinical Response to Single Agent Talazoparib	88 percentage of tumor volume shrinkage Interval 30.0 to 98.0	—

Adverse Events

Talazoparib (2 Months)

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Expansion Arm Talazoparib (6 Months) + Surgery

Serious events: 1 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Talazoparib (2 Months) n=13 participants at risk Talazoparib was administered as single-agent oral dose of 1 mg per day for six cycles (each cycle was 28 days) for 2 months followed by standard of care chemotherapy.	Expansion Arm Talazoparib (6 Months) + Surgery n=20 participants at risk Talazoparib will be administered orally at 1 mg per day for at least 4 and up to 6 cycles. Each cycle will consist of 28 days (+/-3 days) followed by surgery or standard of care chemotherapy.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/13 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year	5.0% 1/20 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year

Other adverse events

Additional Information

Dr. Jennifer Litton,VP, Clinical Research, VP Clinical Research

UT MD Anderson Cancer Center

Phone: (713) 792-2817

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Talazoparib (2 Months) n=13 participants at risk Talazoparib was administered as single-agent oral dose of 1 mg per day for six cycles (each cycle was 28 days) for 2 months followed by standard of care chemotherapy.	Expansion Arm Talazoparib (6 Months) + Surgery n=20 participants at risk Talazoparib will be administered orally at 1 mg per day for at least 4 and up to 6 cycles. Each cycle will consist of 28 days (+/-3 days) followed by surgery or standard of care chemotherapy.
Blood and lymphatic system disorders Anemia	69.2% 9/13 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year	75.0% 15/20 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year
Blood and lymphatic system disorders Leukopenia	61.5% 8/13 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year	0.00% 0/20 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year
Blood and lymphatic system disorders Neutropenia (decreased ANC)	53.8% 7/13 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year	35.0% 7/20 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year
Blood and lymphatic system disorders Thrombocytopenia	38.5% 5/13 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year	5.0% 1/20 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year
Gastrointestinal disorders Mucositis/mouth sore	38.5% 5/13 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year	0.00% 0/20 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year
Nervous system disorders Dizziness	61.5% 8/13 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year	30.0% 6/20 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year
General disorders Fatigue	53.8% 7/13 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year	70.0% 14/20 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year
Gastrointestinal disorders Nausea	53.8% 7/13 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year	75.0% 15/20 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year
Investigations Elevated ALT/AST	30.8% 4/13 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year	0.00% 0/20 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year
Respiratory, thoracic and mediastinal disorders Dyspnea	23.1% 3/13 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year	25.0% 5/20 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year
Gastrointestinal disorders GI disorder (stomach cramps/pain)	23.1% 3/13 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year	0.00% 0/20 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year
Nervous system disorders Headache	23.1% 3/13 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year	10.0% 2/20 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year
Blood and lymphatic system disorders Hyperbilirubinemia	15.4% 2/13 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year	0.00% 0/20 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year
Nervous system disorders Memory impairment	15.4% 2/13 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year	0.00% 0/20 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year
Blood and lymphatic system disorders Hypomagnesemia	15.4% 2/13 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year	15.0% 3/20 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year
Skin and subcutaneous tissue disorders Alopecia	15.4% 2/13 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year	55.0% 11/20 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year
Gastrointestinal disorders Constipation	15.4% 2/13 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year	10.0% 2/20 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year
Gastrointestinal disorders Dry mouth	7.7% 1/13 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year	0.00% 0/20 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year
Eye disorders Eye redness/pain	7.7% 1/13 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year	0.00% 0/20 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year
Metabolism and nutrition disorders Hyperkalemia	7.7% 1/13 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year	5.0% 1/20 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year
Blood and lymphatic system disorders Hypokalemia	7.7% 1/13 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year	5.0% 1/20 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year
Musculoskeletal and connective tissue disorders Myalgia	7.7% 1/13 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year	0.00% 0/20 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year
Skin and subcutaneous tissue disorders Nail discoloration	7.7% 1/13 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year	0.00% 0/20 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year
Nervous system disorders Neuropathy	7.7% 1/13 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year	0.00% 0/20 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year
Skin and subcutaneous tissue disorders Rash	7.7% 1/13 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year	0.00% 0/20 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year
Blood and lymphatic system disorders Decreased white blood cells	61.5% 8/13 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year	60.0% 12/20 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year
Blood and lymphatic system disorders Neutropenia	53.8% 7/13 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year	35.0% 7/20 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year
Blood and lymphatic system disorders Hyperglycemia	0.00% 0/13 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year	25.0% 5/20 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year
General disorders Pain	0.00% 0/13 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year	25.0% 5/20 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year
General disorders Pain in breast	0.00% 0/13 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year	20.0% 4/20 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year
General disorders Increased transaminases	30.8% 4/13 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year	20.0% 4/20 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year
Gastrointestinal disorders Vomiting	0.00% 0/13 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year	15.0% 3/20 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year
Renal and urinary disorders Urinary tract infection	0.00% 0/13 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year	15.0% 3/20 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year
Investigations Increased Creatinine	0.00% 0/13 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year	5.0% 1/20 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year
General disorders Increased Phosphorous	0.00% 0/13 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year	5.0% 1/20 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year
Renal and urinary disorders Increased Blood Urea Nitrogen (BUN)	0.00% 0/13 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year	5.0% 1/20 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year
Blood and lymphatic system disorders Hypophosphatemia	0.00% 0/13 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year	5.0% 1/20 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year
Nervous system disorders Anxiety	0.00% 0/13 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year	5.0% 1/20 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year
Reproductive system and breast disorders Vaginal Bleeding	0.00% 0/13 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year	5.0% 1/20 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year
Respiratory, thoracic and mediastinal disorders Bronchitis	0.00% 0/13 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year	5.0% 1/20 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year
Blood and lymphatic system disorders Hyperphoshatemia	0.00% 0/13 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year	5.0% 1/20 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year
Gastrointestinal disorders Flatulence	0.00% 0/13 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year	5.0% 1/20 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year
Infections and infestations Sinusitis	0.00% 0/13 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year	10.0% 2/20 • Adverse events were monitored from date of consent to date patients started new treatment, an average of 1 year