Breast AdenocarcinomaPhase 2NCT02282345
Talazoparib Before Standard Therapy in Treating Patients With Invasive, BRCA-Mutated Breast Cancer
A Phase 2 study testing Laboratory Biomarker Analysis and Talazoparib in people with Breast Adenocarcinoma and Deleterious BRCA1 Gene Mutation, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
This phase II trial studies the side effects of talazoparib when given before standard therapy in treating patients with breast cancer that has spread to nearby healthy tissue and has a mutation in a breast cancer, early onset (BRCA) gene. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Adenocarcinoma, Deleterious BRCA1 Gene Mutation, Deleterious BRCA2 Gene Mutation
- What is being tested?
- Laboratory Biomarker Analysis and Talazoparib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Apr 2015to 7 Jun 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed written informed consent
- Histologically confirmed primary invasive adenocarcinoma of the breast with the size of the primary tumor being at least 1 cm on imaging by either mammography, ultrasound or breast magnetic resonance imaging (MRI)
- Negative human epidermal growth factor receptor 2 (HER-2)/neu- disease defined as patients with fluorescence in situ hybridization (FISH) ratio < 2.0 or < 6.0 HER2 gene copies per nucleus, and IHC staining scores of 0, 1+, or 2+
- No treatment for current primary invasive adenocarcinoma of the breast such as irradiation, chemotherapy, immunotherapy, investigational therapy or surgery; previous treatment for breast and/or ovarian cancer with chemotherapy, endocrine therapy, surgery and radiation are allowed if >= 3 years prior to current diagnosis and there is no clinical evidence of metastatic disease
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- Baseline multi gated acquisition scan (MUGA) or echocardiogram scans with left ventricular ejection fraction (LVEF) of > 50%
Show all 16Show fewer
- Absolute neutrophil count (ANC) >= 1,500/uL
- Platelets >= 100,000/uL
- Hemoglobin (Hgb) >= 9 g/dL
- Creatinine clearance > 50 ml/min
- Total bilirubin =< 1.5 X upper limit of normal (ULN)
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 X ULN
- Negative serum or urine pregnancy test for women within 7 days of receiving the first dose of the study medication for women of childbearing potential; women will be considered not of childbearing potential and exempt from pregnancy testing if they are either a) older than 50 and amenorrheic for at least 12 consecutive months following cessation of all exogenous hormonal treatments, or b) have documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy, but not tubal ligation
- Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 8 weeks after the last dose of investigational product; men on study also must be using contraception
- Identified deleterious mutation in BRCA 1 or 2 genes (this does not include variants of uncertain significance)
- Eligible to receive standard of care chemotherapy and/or surgery based upon standard practices or institutional guidelines
Who cannot join
- Women who are pregnant (including positive pregnancy test at enrollment or prior to study drug administration) or breast-feeding
- Disease free of prior malignancy for < 3 years with the exception of curatively treated basal carcinoma of the skin or carcinoma in situ of the cervix
- Any other previous antitumor therapies for the current cancer event
- Has had major surgery within 21 days before cycle 1 day 1
- Gastrointestinal tract disease or defect with associated malabsorption syndrome
- Uncontrolled inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
Show all 17Show fewer
- Myocardial infarction within 6 months before starting therapy, symptomatic congestive heart failure (New York Heart Association > class II), unstable angina, or unstable cardiac arrhythmia requiring medication
- Serious intercurrent infections or non-malignant medical illness that are uncontrolled or the control of which may be jeopardized by this therapy
- Psychiatric disorders or other conditions rendering the subject incapable of complying with the requirements of the protocols
- Unable to take oral medications
- Known to be human immunodeficiency virus positive
- Known active hepatitis C virus, or known active hepatitis B virus
- Concurrent disease or condition that would interfere with study participation or safety, such as any of the following:
- Active, clinically significant infection either grade > 2 by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.03 or requiring the use of parenteral anti-microbial agents within 14 days before day 1 of study drug
- Clinically significant bleeding diathesis or coagulopathy, including known platelet function disorders
- Non-healing wound, ulcer, or bone fracture
- Known hypersensitivity to any of the components of talazoparib
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Pilot Study of Talazoparib as a Neoadjuvant Study in Patients With a Diagnosis of Invasive Breast Cancer and a Deleterious BRCA Mutation
This phase II trial studies the side effects of talazoparib when given before standard therapy in treating patients with breast cancer that has spread to nearby healthy tissue and has a mutation in a breast cancer, early onset (BRCA) gene. Talazoparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth, and may be especially effective in patients with BRCA mutations. It is not yet known whether adding talazoparib before standard treatment is safe in treating patients with BRCA mutated breast cancer.
Read the detailed description
PRIMARY OBJECTIVES:
- To evaluate the feasibility of using talazoparib prior to initiating standard neoadjuvant therapies.
II. To evaluate the toxicity profile in women taking talazoparib in the neoadjuvant setting.
SECONDARY OBJECTIVES:
- To provide first estimate of clinical response to talazoparib in the neoadjuvant setting in a pilot trial setting.
II. To evaluate biomarkers of therapy efficacy as well as initiate patient derived xenograft (PDX) models: targeted or whole exome sequencing for BRCA pathway mutations and other somatic and germline alterations; ribonucleic acid (RNA) sequencing; evaluation of changes in immune response; transcriptional profile to assess triple negative breast cancer (TNBC) subtype, BRCA-ness signature and putative PARP sensitivity predictors; functional proteomics with reverse phase protein array (RPPA); generate PDX models and mammosphere cultures from patient derived tumors; PTEN, gamma-H2A histone family, member x (gamma-H2A.X), Ki-67 and cleaved caspase 3 by immunohistochemistry (IHC).
OUTLINE:
Patients receive talazoparib orally (PO) once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then proceed to the standard of care therapy of the treating physician's choice.
After completion of study treatment, patients are followed up until the day after definitive breast surgery.
- Conditions
- Breast Adenocarcinoma, Deleterious BRCA1 Gene Mutation, Deleterious BRCA2 Gene Mutation, HER2/Neu Negative, Invasive Breast Carcinoma
- Being tested
- Laboratory Biomarker Analysis, Talazoparib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Laboratory Biomarker AnalysisOther
Correlative studies
TalazoparibDrug
Also called BMN 673, BMN-673
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Treatment (talazoparib) | Experimental | Patients receive talazoparib PO QD on days 1-28. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then proceed to the standard of care therapy of the treating physician's choice.
This arm was concluded early after 13 patients. An expansion arm of 20 patients was opened in August 2016 to include at least 4 and up to 6 cycles of talazoparib, followed by surgery to estimate residual cancer burden after therapy with single-agent talazoparib. Receives: Other: Laboratory Biomarker Analysis; Drug: Talazoparib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Overall Pathological Complete Response (pCR)
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.
Measured: Up to 6 months
Number of Participants With Grade 4 Toxicities
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.
Measured: up to 6 months
Secondary outcomes (1)
Median Clinical Response to Single Agent Talazoparib
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.
Measured: 2 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2014 (estimated)
- Study start16 Apr 2015
- Primary completion26 Apr 2018
- Study completion7 Jun 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Breast AdenocarcinomaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Jennifer K Litton, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02282345
- Sponsor's protocol ID
- 2014-0045
- Other IDs
- NCI-2015-00335, 2014-0045
- Status last verified
- Jun 2022
- First submitted
- 30 Oct 2014
- Last updated
- 6 Jul 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Kumar T, Hobbs E, Yang F, Chang JT, Contreras A, Cuentas ERP, Garber H, Lee S, Lu Y, Scoggins ME, Adrada BE, Whitman GJ, Arun BK, Mittendorf EA, Litton JK. Tumor Immune Microenvironment Changes by Multiplex Immunofluorescence Staining in a Pilot Study of Neoadjuvant Talazoparib for Early-Stage Breast Cancer Patients with a Hereditary BRCA Mutation. Clin Cancer Res. 2022 Sep 1;28(17):3669-3676. doi: 10.1158/1078-0432.CCR-21-1278.
PubMed 35736816Litton JK, Scoggins ME, Hess KR, Adrada BE, Murthy RK, Damodaran S, DeSnyder SM, Brewster AM, Barcenas CH, Valero V, Whitman GJ, Schwartz-Gomez J, Mittendorf EA, Thompson AM, Helgason T, Ibrahim N, Piwnica-Worms H, Moulder SL, Arun BK. Neoadjuvant Talazoparib for Patients With Operable Breast Cancer With a Germline BRCA Pathogenic Variant. J Clin Oncol. 2020 Feb 10;38(5):388-394. doi: 10.1200/JCO.19.01304. Epub 2019 Aug 28.
PubMed 31461380
Study at a glance
From the registry record, last updated by the sponsor on 6 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Talazoparib as a Neoadjuvant Study in Patients With a Diagnosis of Invasive Breast Cancer and a Deleterious BRCA Mutation
- ClinicalTrials.gov ID
- NCT02282345
- Acronym / sponsor ID
- 2014-0045
- Conditions
- Breast Adenocarcinoma, Deleterious BRCA1 Gene Mutation, Deleterious BRCA2 Gene Mutation, HER2/Neu Negative, Invasive Breast Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 16 Apr 2015 (actual)
- Primary completion
- 26 Apr 2018 (actual)
- Study completion
- 7 Jun 2022 (actual)
- First posted
- 4 Nov 2014 (estimated)
- Results
- Posted 10 Feb 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial studies the side effects of talazoparib when given before standard therapy in treating patients with breast cancer that has spread to nearby healthy tissue and has a mutation in a breast cancer, early onset (BRCA) gene. Talazoparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth, and may be especially effective in patients with BRCA mutations. It is not yet known whether adding talazoparib before standard treatment is safe in treating patients with BRCA mutated breast cancer.
Detailed description
PRIMARY OBJECTIVES:
- To evaluate the feasibility of using talazoparib prior to initiating standard neoadjuvant therapies.
II. To evaluate the toxicity profile in women taking talazoparib in the neoadjuvant setting.
SECONDARY OBJECTIVES:
- To provide first estimate of clinical response to talazoparib in the neoadjuvant setting in a pilot trial setting.
II. To evaluate biomarkers of therapy efficacy as well as initiate patient derived xenograft (PDX) models: targeted or whole exome sequencing for BRCA pathway mutations and other somatic and germline alterations; ribonucleic acid (RNA) sequencing; evaluation of changes in immune response; transcriptional profile to assess triple negative breast cancer (TNBC) subtype, BRCA-ness signature and putative PARP sensitivity predictors; functional proteomics with reverse phase protein array (RPPA); generate PDX models and mammosphere cultures from patient derived tumors; PTEN, gamma-H2A histone family, member x (gamma-H2A.X), Ki-67 and cleaved caspase 3 by immunohistochemistry (IHC).
OUTLINE:
Patients receive talazoparib orally (PO) once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then proceed to the standard of care therapy of the treating physician's choice.
After completion of study treatment, patients are followed up until the day after definitive breast surgery.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (talazoparib) | Experimental | Other: Laboratory Biomarker Analysis, Drug: TalazoparibPatients receive talazoparib PO QD on days 1-28. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then proceed to the standard of care therapy of the treating physician's choice. This arm was concluded early after 13 patients. An expansion arm of 20 patients was opened in August 2016 to include at least 4 and up to 6 cycles of talazoparib, followed by surgery to estimate residual cancer burden after therapy with single-agent talazoparib. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Signed written informed consent
- Histologically confirmed primary invasive adenocarcinoma of the breast with the size of the primary tumor being at least 1 cm on imaging by either mammography, ultrasound or breast magnetic resonance imaging (MRI)
- Negative human epidermal growth factor receptor 2 (HER-2)/neu- disease defined as patients with fluorescence in situ hybridization (FISH) ratio < 2.0 or < 6.0 HER2 gene copies per nucleus, and IHC staining scores of 0, 1+, or 2+
- No treatment for current primary invasive adenocarcinoma of the breast such as irradiation, chemotherapy, immunotherapy, investigational therapy or surgery; previous treatment for breast and/or ovarian cancer with chemotherapy, endocrine therapy, surgery and radiation are allowed if >= 3 years prior to current diagnosis and there is no clinical evidence of metastatic disease
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
Key exclusion criteria (17 listed)
- Women who are pregnant (including positive pregnancy test at enrollment or prior to study drug administration) or breast-feeding
- Disease free of prior malignancy for < 3 years with the exception of curatively treated basal carcinoma of the skin or carcinoma in situ of the cervix
- Any other previous antitumor therapies for the current cancer event
- Has had major surgery within 21 days before cycle 1 day 1
- Gastrointestinal tract disease or defect with associated malabsorption syndrome
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (talazoparib) |
| TalazoparibAlso: BMN 673, BMN-673Given PO | Drug | Treatment (talazoparib) |
Primary outcome
Number of Participants With Overall Pathological Complete Response (pCR)
Time frame: Up to 6 months
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.
Number of Participants With Grade 4 Toxicities
Time frame: 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.
1 secondary outcome
Median Clinical Response to Single Agent Talazoparib
Time frame: 2 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jul 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35736816Kumar T, Hobbs E, Yang F, Chang JT, Contreras A, Cuentas ERP, Garber H, Lee S, Lu Y, Scoggins ME, Adrada BE, Whitman GJ, Arun BK, Mittendorf EA, Litton JK. Tumor Immune Microenvironment Changes by Multiplex Immunofluorescence Staining in a Pilot Study of Neoadjuvant Talazoparib for Early-Stage Breast Cancer Patients with a Hereditary BRCA Mutation. Clin Cancer Res. 2022 Sep 1;28(17):3669-3676. doi: 10.1158/1078-0432.CCR-21-1278.
- Derived from this study: PubMed 31461380Litton JK, Scoggins ME, Hess KR, Adrada BE, Murthy RK, Damodaran S, DeSnyder SM, Brewster AM, Barcenas CH, Valero V, Whitman GJ, Schwartz-Gomez J, Mittendorf EA, Thompson AM, Helgason T, Ibrahim N, Piwnica-Worms H, Moulder SL, Arun BK. Neoadjuvant Talazoparib for Patients With Operable Breast Cancer With a Germline BRCA Pathogenic Variant. J Clin Oncol. 2020 Feb 10;38(5):388-394. doi: 10.1200/JCO.19.01304. Epub 2019 Aug 28.
- University of Texas MD Anderson Cancer Center WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jennifer K Litton principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Laboratory Biomarker Analysis and Talazoparib in people with Breast Adenocarcinoma and Deleterious BRCA1 Gene Mutation, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Feb 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Overall Pathological Complete Response (pCR) (time frame: Up to 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02282345, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jul 2022.