Pre-Operative Radiation With Incomplete Neo-Adjuvant Chemotherapy for Breast Cancer

Inclusion Criteria:

Primary Study Subjects (Consent A) Inclusion Criteria for Observation

• Patient must be 18 years of age or older
• Patients must have histologically confirmed (by routine H&E staining) adenocarcinoma of the breast.
• Patients must have an axillary nodal evaluation either by FNA or SNB in accordance with their institutional guidelines.
• Patients with squamous, or metaplastic carcinomas or sarcomas of the breast are NOT eligible
• Patient must have a history and physical within 8 weeks prior to the start of any protocol therapy
• Patient must have had a bilateral mammogram prior to surgery unless there is only one breast.
• Patient must have a Medical Oncology consult and be recommended to receive neoadjuvant chemotherapy for a stage II through IV carcinoma.
• Patients must have a performance status 0 or 1 by ECOG criteria (Appendix)
• Patients must not have received prior radiation therapy to the involved breast at any time for any reason.

Secondary Study Subjects (Consent B) Inclusion Criteria for Treatment with Veliparib and Radiation

• Patient must have > 1.0 cm residual in-breast cancer and/or clinically positive residual nodal disease.
• Hematology:

Absolute Neutrophil Count (ANC) ≥ 1000/mm3 Platelet Count ≥ 100,000/mm3 Hemoglobin ≥ 9.0 g/dL (after transfusion if required)

- Renal Function: Creatinine Serum ≤ 2.0 mg/dl or Creatinine Clearance ≥45mL/min

- Hepatic Function: Bilirubin ≤ 1.5 mg/dL (≤ 3.0 mg/dL with liver metastasis) Serum Glutamic-Oxaloacetic Transaminase (SGOT) ≤ 2.5 × ULN (≤ 5.0 × ULN with liver metastasis) Serum Glutamic-Pyruvic Transaminase (SGPT) ≤ 2.5 × ULN (≤ 5.0 × ULN with liver metastasis) ULN = Upper normal limit of institution's normal range

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

2. Subjects with Gilbert's disease may have bilirubin up to 2.5 mg/dL (or 3.0 mg/dL with liver ( metastasis).

   • Patients must not be pregnant due to the potential for fetal harm as a result of this treatment regimen. Women of child-bearing potential must also have a negative pregnancy test within six weeks prior to start of protocol therapy.
   • No other prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or any other cancer from which the patient has been disease-free for 5 years.
   • Women of childbearing potential must agree to use adequate contraception (one of the following listed below) prior to study entry, for the duration of study participation and up to 2 months following completion of protocol therapy

a. Total abstinence from sexual intercourse (minimum one complete menstrual cycle) b. A vasectomized partner c. Hormonal contraceptives (oral, parenteral or transdermal) for at least 3 months prior to study drug administration d. Double-barrier metho (condoms, contraceptive sponge, diaphragm or vaginal ring with spermicidal jellies or cream)

• Patients must not have a serious medical or psychiatric illness which prevents informed consent or compliance with treatment.
• All patients must be informed of the investigational nature of this study and given written informed consent in accordance with institutional and federal guidelines.

Exclusion Criteria:

• Women who were cT1-2 and cN0 before NAC and already planned to have a mastectomy. (This group would likely not receive radiation standardly)
• Last dose of chemotherapy, immunotherapy, biologic therapy, or investigational therapy, was less than 14 days prior to enrollment on POPI.
• Bisphosphonates, hormone modification therapy, and trastuzumab are permitted without restriction.
• Unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or prior anti-cancer treatment.
• If female, subject is pregnant or breast-feeding

• Clinically significant and uncontrolled major cardiac, respiratory, renal, hepatic, gastrointestinal, hematologic or neurological/psychiatric disease or disorder,including but not limited to:

  1. active uncontrolled infection
  2. symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia
  3. any other illness condition(s) that could exacerbate potential toxicities, confound safety assessments, require excluded therapy for management, or limit compliance with study requirements. Questions regarding inclusion of individual subjects should be directed to the PI.
• Unable to swallow and retain oral medications.

• Known contraindication to enhanced MRI and CT, including but not limited to:

  1. Presence of metal objects within the body such as a cardiac pacemaker, implanted cardiac defibrillator, brain aneurysm clips, cochlear implant, ocular foreign body, or shrapnel.
  2. History of immediate or delayed hypersensitivity reaction or other contraindication to contrast agents including but not limited to gadolinium and iodine.
• Previous enrollment in this study or another study involving the investigation of Veliparib (ABT-888), with the exception of receiving a single dose of study drug.
• Consideration by the Investigator, for any reason, that the subject is an unsuitable candidate to receive Veliparib (ABT-888) and/or breast irradiation.
• For purposes of this protocol, anti-tumor treatment may be defined as, but is not limited to, anti-cancer agents (cytotoxic chemotherapy, immunotherapy, biologic therapy), radiotherapy, and investigational agents. An investigational agent is any drug or therapy not currently approved for use in humans.

NOTE:

• Anti-cancer Agents: Anti-cancer agents are not permitted within 14 days prior to start of POPI. There are no limitations on the type or number of prior regimens.
• Radiation: Prior treatment with breast irradiation is not allowed due to the potential for cumulative toxicities.
• Surgery: Incident breast biopsies only permitted prior to POPI to confirm residual disease after NAC.