A Study of Rucaparib Administered With Radiation in Patients With Triple Negative Breast Cancer With an Incomplete Response Following Chemotherapy

Inclusion Criteria:

- Female, ≥ 18 years of age.

- Non-metastatic, histologically or cytologically-confirmed TNBC (defined as ER <1%, PR
<1%, her-2-neu 0-1+ by IHC or FISH-negative or as per MD discretion).

- Definitive surgical treatment with breast-conserving surgery or mastectomy and
axillary lymph node evaluation.

- Residual disease in the breast or lymph nodes at the time of definitive surgical
treatment.

- At least 6-month life expectancy, ECOG Performance status < 2.

- Willingness to discontinue any cytotoxic chemotherapeutic agents, immunotherapy and
biologic therapy at least 2 weeks prior to the start of RT.

- Adequate organ function (assessed within 30 days prior to initiation of protocol
treatment, unless otherwise indicated) as follows: Hematology

- Absolute Neutrophil Count (ANC) ≥1500/mm^3

- Platelet Count ≥100,000/mm^3

- Hemoglobin ≥9.0 g/dL (after transfusion if required) Renal Function

- Creatinine Serum ≤ 1.5 mg/dL or Creatinine Clearance ≥ 45 mL/min^a Hepatic
Function

- Bilirubin ≤ 1.5 mg/dL

- Aspartate Aminotransferase (AST) ≤ 2.5 x ULN^b

- Alanine Aminotransferase (ALT) ≤ 2.5 x ULN ULN = upper normal limit of
institution's normal range

1. If calculated creatinine clearance is < 45mL/min, a 24-hour urine collection
for creatinine clearance may be performed

2. Subjects with documented Gilbert's disease may have bilirubin up to 2.5
mg/dL

- Negative serum pregnancy test within 14 days prior to study treatment if a woman has
child-bearing potential. Subjects of child bearing potential are those who have not
been surgically sterilized or have not been free from menses for > 1 year.

- Ability to swallow and retain oral medications.

- Written informed consent obtained from subject and ability for subject to comply with
the requirements of the study.

- Female subjects of childbearing potential should be willing to use 2 methods of birth
control or be surgically sterile, or abstain from heterosexual activity for the
duration of study participation. Should a woman become pregnant while participating on
study, she should inform the treating physician immediately.

Exclusion Criteria:

- Gross residual tumor or positive margins after surgery that is un-excised, as
radiation dose in the study will be limited to 60 Gy.

- Complete pathologic response to NAC.

- Receipt of PARP inhibitor prior to RT.

- Pregnant or expecting to conceive within the projected duration of the trial, starting
with screening visit through 180 days after the last dose of trial treatment.

- Prior history of radiation therapy to the ipsilateral breast and/or regional nodes is
not allowed (prior RT to other sites is permitted).

- Patients with breast implants are excluded.

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to rucaparib.

- Concomitant anti-neoplastic treatment is not allowed during protocol treatment and
should be completed at least 2 weeks prior to commencement of protocol treatment, with
resolution of associated acute toxicities. Bisphosphonates are permitted without
restriction even during protocol treatment.

- Significant comorbidity: Patients with clinically significant and uncontrolled major
disease or disorder that could exacerbate potential toxicities, confound safety
assessments, require excluded therapy for management, or limit study compliance.

- Ongoing therapy with other investigational agents. Patients may not be receiving any
other investigational agents.

- Unresolved toxicity from other agents. Patients with unresolved CTCAE v4.03 Grade 3 or
greater toxicity from prior administration of another investigational drug and/or
anti-cancer treatment are not eligible.