Pre-Operative Radiation and Veliparib for Breast Cancer

NCT01618357 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: J111551503214668
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 6

Brief Summary

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

Conditions

Breast Cancer

Keywords

Veliparib; ABT-888; Radiation; POPI

Outcome Measures

Primary Outcomes (1)

• 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

Other Outcomes (10)

• Biomarkers

  baseline

• Biomarkers

  Cycle 1 (each cycle is 29 days)

• Biomarkers

  Cycle 2 (each cycle is 29 days)

Study Arms (1)

Intervention

EXPERIMENTAL

All subjects will receive pre-operative Neo-Adjuvant Chemotherapy (NAC) but only those with an incomplete response to NAC will be treated with the PARPi experimental portion of the trial explained below. Those with a complete response will be treated per standard of care.

Radiation: Radiation; Procedure: Lumpectomy/Mastectomy; Drug: Veliparib

Interventions

Radiation RADIATION

Patients will receive radiation therapy at a dose of 2.35 Gy per fraction to the breast and regional nodal region for 16 fractions to a total dose of 37.5 Gy. Treatments will be given Monday through Friday. Radiation therapy will start on day 1 of Veliparib.

Intervention

Lumpectomy/Mastectomy PROCEDURE

Resection of breast cancer.

Intervention

Veliparib DRUG

Pills to be taken twice a day during radiation and for one week after completion of radiation for a total of 29 days.

Intervention

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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:
• Absolute Neutrophil Count (ANC) ≥ 1000/mm3
• Platelet Count ≥ 100,000/mm3
• 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:
• Bilirubin ≤ 1.5 mg/dL (≤ 3.0 mg/dL with liver metastasis)

You may not qualify if:

• 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:
• Active uncontrolled infection
• Symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia
• Unable to swallow and retain oral medications.
• History of seizure disorder.
• Known contraindication to enhanced MRI and CT, including but not limited to:
• 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.
• 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.

Sponsors & Collaborators

• Richard Zellars: lead

Study Sites (6)

I U Health West

Avon, Indiana, 46123, United States

Location

IU Schwarz Cancer Center

Carmel, Indiana, 46032, United States

Location

Indiana University Health Hospital

Indianapolis, Indiana, 46202, United States

Location

Indiana University Health Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Indiana University Health Methodist Hospital

Indianapolis, Indiana, 46202, United States

Location

Sidney and Lois Eskenazi Hospital

Indianapolis, Indiana, 46202, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Radiation; Mastectomy, Segmental; Mastectomy; veliparib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Physical Phenomena; Surgical Procedures, Operative

Study Officials

• Richard Zellars, MD

  Indiana University School of Medicine, Indiana University Simon Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor and Chairman of the Department of Radiation Oncology

Model Details: A dose finding trial to assess the acute and late toxicity of pre-operative PARPi and concurrent radiation in women with stage II-IV invasive breast cancer who have had an incomplete response to NAC. Our primary goal is to assess the acute toxicity a dose finding trial to assess the acute and late toxicity of pre-operative of this combined modality therapy.

Study Record Dates

• First Submitted: January 20, 2012
• First Posted: June 13, 2012
• Study Start: July 22, 2013
• Primary Completion: September 6, 2023
• Study Completion: October 17, 2023
• Last Updated: May 22, 2024

Record last verified: 2024-05

Locations

US (6)