NCT01618357

Pre-Operative Radiation and Veliparib for Breast Cancer

Completed Phase 1 Last updated 22 May 2024

What this trial tests

Phase 1 trial testing Radiation in Breast Cancer in 19 participants. Completed in 17 October 2023.

Timeline

22 July 2013

Primary endpoint
6 September 2023

17 October 2023

Quick facts

Lead sponsor	Richard Zellars
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	19
Start date	22 July 2013
Primary completion	6 September 2023
Estimated completion	17 October 2023
Sites	6 locations across United States

Drugs / interventions tested

• Radiation
• Lumpectomy/Mastectomy
• Veliparib — full drug profile →

Conditions studied

• Breast Cancer — all drugs for Breast Cancer →

Sponsor

Richard Zellars

Who can join

18 and older, female only, with Breast Cancer. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. PARP inhibitor resistance: the underlying mechanisms and clinical implications.
   Li H, Liu ZY, Wu N, Chen YC, et al · · 2020 · cited 379× · PMID 32563252 · DOI 10.1186/s12943-020-01227-0
2. Targeting DNA damage response in cancer therapy.
   Hosoya N, Miyagawa K. · · 2014 · cited 232× · PMID 24484288 · DOI 10.1111/cas.12366
3. How shall we treat early triple-negative breast cancer (TNBC): from the current standard to upcoming immuno-molecular strategies.
   Park JH, Ahn JH, Kim SB. · · 2018 · cited 109× · PMID 29765774 · DOI 10.1136/esmoopen-2018-000357
4. Combination strategies with PARP inhibitors in BRCA-mutated triple-negative breast cancer: overcoming resistance mechanisms.
   Jain A, Barge A, Parris CN. · · 2025 · cited 44× · PMID 39572842 · DOI 10.1038/s41388-024-03227-6
5. BRCA 1/2-Mutation Related and Sporadic Breast and Ovarian Cancers: More Alike than Different.
   Burgess M, Puhalla S. · · 2014 · cited 34× · PMID 24579064 · DOI 10.3389/fonc.2014.00019
6. Optimizing Radiation Therapy to Boost Systemic Immune Responses in Breast Cancer: A Critical Review for Breast Radiation Oncologists.
   Ho AY, Wright JL, Blitzblau RC, Mutter RW, et al · · 2020 · cited 32× · PMID 32417409 · DOI 10.1016/j.ijrobp.2020.05.011
7. PARP Inhibitors in the Treatment of Early Breast Cancer: The Step Beyond?
   Gonçalves A, Bertucci A, Bertucci F. · · 2020 · cited 26× · PMID 32471249 · DOI 10.3390/cancers12061378
8. Perspectives on the combination of radiotherapy and targeted therapy with DNA repair inhibitors in the treatment of pancreatic cancer.
   Yang SH, Kuo TC, Wu H, Guo JC, et al · · 2016 · cited 24× · PMID 27621574 · DOI 10.3748/wjg.v22.i32.7275