Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 3, Multi-Center, Open-Label, Randomized Study of Gemcitabine/Carboplatin, With or Without BSI-201, in Patients With ER-, PR-, and Her2-Negative Metastatic Breast Cancer
Brief Summary: The goal of this study was to determine the effect on overall survival and progression free survival by adding iniparib (BSI-201/SAR240550) to the combination of gemcitabine/carboplatin in adult patients with triple negative breast cancer (estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and human epidermal growth factor receptor 2 (HER2)-negative).

Based on data generated by BiPar/Sanofi, it is concluded that iniparib does not possess characteristics typical of the poly (ADP-ribose) polymerase (PARP) inhibitor class. The exact mechanism has not yet been fully elucidated, however based on experiments on tumor cells performed in the laboratory, iniparib is a novel investigational anti-cancer agent that induces gamma-H2AX (a marker of DNA damage) in tumor cell lines, induces cell cycle arrest in the G2/M phase in tumor cell lines, and potentiates the cell cycle effects of DNA damaging modalities in tumor cell lines. Investigations into potential targets of iniparib and its metabolites are ongoing.


Options:
A: Inclusion Criteria:

* Metastatic or locally advanced, histologically documented TNBC characterized by absence of human epidermal growth factor 2 (HER2), estrogen receptor (ER), and progesterone receptor (PR) expression
* No prior chemotherapy or targeted systemic therapy for inoperable locally advanced or metastatic TNBC
* Eligible for taxane monotherapy (i.e., absence of rapid clinical progression, life-threatening visceral metastases, or the need for rapid symptom and/or disease control)
* A representative formalin-fixed, paraffin-embedded tumor specimen in paraffin blocks, or at least 20 unstained slides with an associated pathology report documenting ER, PR, and HER2 negativity. Participants with fewer than 20 unstained slides available at baseline, and not fewer than 12 unstained slides will be eligible upon discussion with Medical Monitor
* Eastern Cooperative Oncology Group performance status of 0 or 1
* Measurable disease as defined by RECIST v1.1
* Adequate hematologic and end-organ function

Exclusion Criteria:

* Known central nervous system (CNS) disease, except for treated asymptomatic CNS metastases
* Leptomeningeal disease
* Pregnancy or lactation
* History of autoimmune disease
* Prior allogeneic stem cell or solid organ transplantation
* Positive test for human immunodeficiency virus
* Active hepatitis B or hepatitis C
* Receipt of a live, attenuated vaccine within 4 weeks prior to randomization, during treatment, or within 5 months following the last dose of atezolizumab/placebo
B: Inclusion Criteria:

* Histologically or cytologically confirmed breast cancer that is either locally recurrent or metastatic.
* Locally recurrent disease must not be amenable to surgical resection or radiation with curative intent.
* Must have a documented deleterious Breast Cancer Gene BRCA1 or BRCA2 germline mutation.
* If Human Epidermal Growth Factor Receptor (HER2) positive, subjects must have received and progressed on at least one prior standard HER2 directed therapy or the subject must be ineligible to receive anti-HER2 therapy.
* Measurable or non-measurable (but radiologically evaluable) disease by RECIST (Response Evaluation Criteria in Solid Tumors) criteria 1.1.
* Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-2.
* Subject must have adequate bone marrow, renal and hepatic function.
* Subject must not be pregnant or plan to conceive a child.

Exclusion Criteria:

* Received anticancer agent(s) or an investigational agent within 21 days prior to C1D1, or radiotherapy within 28 days prior Cycle 1 Day 1.
* More than 2 prior lines of cytotoxic chemotherapy.
* Prior treatment of breast cancer with temozolomide, a platinum agent, or a Poly (ADP ribose) Polymerase (PARP) inhibitor.
* Prior taxane therapy for metastatic breast cancer.
* A history of or evidence of brain metastases or leptomeningeal disease.
* A history of uncontrolled seizure disorder.
* Pre-existing neuropathy from any cause in excess of Grade 1.
* Known history of allergic reaction to cremophor/paclitaxel.
* Clinical significant uncontrolled conditions, active infection, myocardial infarction, stroke, or transient ischemic attack, psychiatric illness/social situations that would limit compliance.
* Pregnant or breastfeeding.
C: Inclusion Criteria:

- Histologically documented breast cancer (either primary or metastatic site) that is ER-negative, PR-negative, and HER2 non-overexpressing by immunohistochemistry (0, 1) or fluorescence in situ hybridization (FISH).

Triple-negative tumors were defined by the following criteria:

* HER2-non-overexpressing: FISH-negative (defined by ratio \<2.2) or, immunohistochemical (IHC) 0, IHC 1+ or, IHC 2+ or IHC 3+ and FISH-negative.
* ER- and PR-negative: \<10% tumor staining by immunohistochemistry (IHC).

  * Never having received chemotherapy for metastatic disease or, having received 1 or 2 prior chemotherapy regimens in the metastatic setting (Prior adjuvant/neoadjuvant therapy was allowed);
  * Metastatic breast cancer (Stage IV) with measurable disease by RECIST 1.1 criteria;
  * Female, ≥18 years of age;
  * Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;
  * Organ and marrow function as follows: absolute neutrophil count (ANC) ≥1500/mm3, platelets ≥100,000/dL, hemoglobin ≥9 g/dL, bilirubin ≤1.5 mg/dL, serum creatinine ≤1.5 mg/dL or creatinine clearance ≥60 mL/min, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 times the upper limit of normal if no liver involvement or ≤5 times the upper limit of normal with liver involvement;
  * Radiation therapy completed at least 14 days before study dosing on day 1; radiated lesions may not have served as measurable disease;
  * Central nervous system metastases allowed if subject did not require steroids, whole brain radiation therapy (XRT), gamma/cyber knife, and brain metastases were clinically stable without symptomatic progression;
  * For women of child bearing potential, documented negative pregnancy test within two weeks of study entry and agreement to acceptable birth control during the duration of the study therapy;
  * Tissue block (primary or metastatic) or readily available fresh frozen tumor tissue for PARP expression and other pharmacogenomic studies recommended (although its absence will not exclude subjects from participating);
  * No other diagnosis of malignancy (with exception of non melanoma skin cancer or a malignancy diagnosed ≥5 years ago);
  * Obtained informed consent;
  * Capability to understand and comply with the protocol and signed informed consent document.

Exclusion Criteria:

* Systemic anticancer therapy within 14 days of the first dose of study drug;
* Prior treatment with gemcitabine, carboplatin, cisplatin or iniparib
* Had not recovered to grade ≤1 from adverse events (AEs) per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v3.0 or to within 10% of baseline values due to investigational drugs or other medications administered more than 30 days prior to study enrollment;
* Major medical conditions that might have affected study participation (e.g. uncontrolled pulmonary, renal, or hepatic dysfunction, uncontrolled infection, cardiac disease);
* Concurrent radiation therapy intended to treat primary tumor not permitted throughout the course of the study; palliative radiation was acceptable;
* Leptomeningeal disease or brain metastases requiring steroids or other therapeutic intervention;
* Pregnancy or breastfeeding;
* Inability or unwillingness to abide by the study protocol or cooperate fully with the investigator or designee.
D: Inclusion Criteria:

* Histologically or cytologically confirmed carcinoma of the breast
* Locally advanced and/or metastatic disease
* Deleterious or pathogenic germline BRCA 1 or BRCA 2 mutation
* Prior chemotherapy: Cohort 1) PR or CR to prior platinum-containing regimen for metastatic disease with disease progression \> 8 weeks following the last dose of platinum; or Cohort 2) \> 2 prior chemotherapy regimens for metastatic disease and no prior platinum for metastatic disease
* ECOG performance status ≤ 1
* Have adequate organ function

Exclusion Criteria:

* Prior enrollment into a clinical trial of a PARP inhibitor
* CNS metastasis except adequately treated brain metastasis documented by baseline CT or MRI scan that has not progressed since previous scans and that does not require corticosteroids for management of CNS symptoms
* Prior malignancy except for prior BRCA-associated cancer as long as there is no current evidence of the prior cancer, carcinoma in situ of the cervix or non-melanoma skin cancer, and a cancer diagnosed and definitively treated \>5 years prior to study enrollment with no subsequent evidence of recurrence
* Known to be HIV positive, active hepatitis C virus, or active hepatitis B virus
* Known hypersensitivity to any of the components of talazoparib

Answer: C