Breast Cancer Clinical Trial
Official title:
Pre-Operative PARPi and Irradiation (POPI) in Women With an Incomplete Response to Neo-Adjuvant Chemotherapy for Breast Cancer
Verified date | July 2023 |
Source | Indiana University |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
The investigators' primary aim is to determine the safety, tolerability and maximum tolerated dose (within 50 - 200mg/BID dose range) when combining veliparib and radiation. The investigators' exploratory aim is to serially assess apoptosis/proliferation biomarkers, and gene and protein expression profiles for correlation with tumor response to POPI. Study Plan: It will be a standard 3+3 dose finding trial in which the MTD will be defined as the dose below the level at which >1 DLT is observed in 3-6 patients. Women with node positive disease prior to NAC and >1.0 cm residual breast disease and/or clinically positive nodal disease after NAC will be offered participation in the research phase of this study. Women with residual disease >1cm or +/-LN after NAC (Med Onc's choice) will be offered pre-operative Veliparib and concurrent whole breast and regional nodal irradiation. Four (4) dose levels of Veliparib will be evaluated with concurrent whole breast and regional nodal irradiation (WB/RNI). The starting dose of Veliparib will be 50 mg BID, will increase in 50 mg increments to a maximum of 200 mg BID and be delivered concurrently with 235 cGy QD x 16 to the breast and SCV/Axilla. Accrual: Up to 41 patients
Status | Suspended |
Enrollment | 41 |
Est. completion date | December 31, 2024 |
Est. primary completion date | December 31, 2023 |
Accepts healthy volunteers | No |
Gender | Female |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria for Observation - Patient must be female and 18 years of age or older. - Patients must have histologically confirmed (by routine H&E staining) adenocarcinoma of the breast or axillary node. Patients with squamous, or metaplastic carcinomas or sarcomas of the breast are NOT eligible. - Patient must have had a bilateral mammogram prior to NAC unless there is only one breast. - Patient must have a Medical Oncology consult and be recommended to receive neoadjuvant chemotherapy for a stage IIB through IV carcinoma. - Patients must not have received prior radiation therapy to the involved breast at any time for any reason due to the potential for cumulative toxicities. Inclusion Criteria for Treatment with Veliparib and Radiation - Patient must have a history and physical within 2 weeks prior to the start of any protocol therapy (radiation and veliparib). - Patient must have > 1.0 cm residual in-breast cancer (via positive biopsy) or clinically positive residual nodal disease. Incident breast biopsies only permitted prior to POPI to confirm residual disease after NAC. - Hematology: 1. Absolute Neutrophil Count (ANC) = 1000/mm3 2. Platelet Count = 100,000/mm3 3. Hemoglobin = 9.0 g/dL (after transfusion if required) - Renal Function: a. Creatinine Serum = 2.0 mg/dl or Creatinine Clearance =45mL/min - Hepatic Function: 1. Bilirubin = 1.5 mg/dL (= 3.0 mg/dL with liver metastasis) 2. Serum Glutamic-Oxaloacetic Transaminase (SGOT) = 2.5 × ULN (= 5.0 × ULN with liver metastasis) 3. Serum Glutamic-Pyruvic Transaminase (SGPT) = 2.5 × ULN (= 5.0 × ULN with liver metastasis) ULN = Upper normal limit of institution's normal range 4. If calculated creatinine clearance is < 45 mL/min, a 24-hour urine collection for creatinine clearance may be performed. 5. 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 2 weeks prior to start of protocol therapy (radiation and veliparib). - 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 1. Total abstinence from sexual intercourse (minimum one complete menstrual cycle) 2. A vasectomized partner 3. Hormonal contraceptives (oral, parenteral or transdermal) for at least 3 months prior to study drug administration 4. Double-barrier method (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. - Patients must have a performance status 0 or 1 by ECOG criteria (Appendix I) Exclusion Criteria for Consent B - Women who have a < 1.0 cm and are cN0 after NAC are not eligible. - Last dose of chemotherapy, immunotherapy, biologic therapy, or investigational therapy, was less than 21 days prior to protocol therapy (radiation and veliparib). There are no limitations on the type or number of prior regimens. Hormonal therapy and Traztusumab are permitted during 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. - History of seizure disorder. - 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 on 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. Inclusion of Underrepresented Populations Individuals of all races and ethnic groups are eligible for this trial. There is no bias towards age or race in the clinical trial outlined. This trial is open to the accrual of women only. |
Country | Name | City | State |
---|---|---|---|
United States | I U Health West | Avon | Indiana |
United States | IU Schwarz Cancer Center | Carmel | Indiana |
United States | Indiana University Health Hospital | Indianapolis | Indiana |
United States | Indiana University Health Melvin and Bren Simon Cancer Center | Indianapolis | Indiana |
United States | Indiana University Health Methodist Hospital | Indianapolis | Indiana |
United States | Sidney and Lois Eskenazi Hospital | Indianapolis | Indiana |
Lead Sponsor | Collaborator |
---|---|
Richard Zellars |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Biomarkers | Serially assess apoptosis/proliferation biomarkers via immunohistochemestry (IHC), gene microarray and proteomic analyses | baseline | |
Other | Biomarkers | Serially assess apoptosis/proliferation biomarkers via immunohistochemestry (IHC), gene microarray and proteomic analyses | Cycle 1 (each cycle is 29 days) | |
Other | Biomarkers | Serially assess apoptosis/proliferation biomarkers via immunohistochemestry (IHC), gene microarray and proteomic analyses | Cycle 2 (each cycle is 29 days) | |
Other | Biomarkers | Serially assess apoptosis/proliferation biomarkers via immunohistochemestry (IHC), gene microarray and proteomic analyses | Cycle 3 (each cycle is 29 days) | |
Other | Biomarkers | Serially assess apoptosis/proliferation biomarkers via immunohistochemestry (IHC), gene microarray and proteomic analyses | Post Radiation (up to 3 months afterwards) | |
Other | Gene and protein expression | Create profiles for correlation with tumor response to POPI via immunohistochemestry (IHC), gene microarray and proteomic analyses | Baseline | |
Other | Gene and protein expression | Create profiles for correlation with tumor response to POPI via immunohistochemestry (IHC), gene microarray and proteomic analyses | Cycle 1 (each cycle is 29 days) | |
Other | Gene and protein expression | Create profiles for correlation with tumor response to POPI via immunohistochemestry (IHC), gene microarray and proteomic analyses | Cycle 2 (each cycle is 29 days) | |
Other | Gene and protein expression | Create profiles for correlation with tumor response to POPI via immunohistochemestry (IHC), gene microarray and proteomic analyses | Cycle 3 (each cycle is 29 days) | |
Other | Gene and protein expression | Create profiles for correlation with tumor response to POPI via immunohistochemestry (IHC), gene microarray and proteomic analyses | Post Radiation (up to 3 months afterwards) | |
Primary | POPI Safety, Tolerability, and MTD | To determine the safety, tolerability and maximum tolerated dose (within 50 - 200 mg/BID dose range) when combining Veliparib and radiation. | 1 year |
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