PARP Inhibition During Pre-surgical Window in Breast/Ovary Cancer

Pre-Surgical Window Pilot Investigation of the Effect of PARP Inhibition on the Cellular and Molecular Changes in Primary Ovarian and Breast Cancer

Study involves surgery for cytoreduction or laparoscopy to determine if you are a candidate for tumor debulking or a tissue biopsy. Following this surgery you will receive chemotherapy. This study will administer 7 days of treatment with a targeted therapy called Lynparza. Lynparza and/or other PARP inhibitors have been FDA approved for the treatment of ovarian and breast cancer. Tissue biopsy will be done before a 7 day course of Lynparza in order to correlate molecular changes to response to treatment. Participation in this trial will require an additional tumor biopsy which will occur either before or after treatment of Lynparza.

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Ovarian Cancer
• Intervention / Treatment: Drug: Lynparza

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• All patients must have cytology/ biopsy proven diagnosis of a mullerian carcinoma, high clinical index of suspicion for ovarian cancer OR triple negative, BRCA mutated breast cancer.
• Patients may not have received prior treatment for breast or ovarian cancer.
• All patients must be of at least 18 years of age.
• ECOG Performance status must be 0,1 or 2.
• Patients must not have received a prior PARP inhibitor
• Adequate organ and marrow function as defined below:
• absolute neutrophil count >/= 1500/mcL
• Platelets > /= 100,000 /mcl
• Hemoglobin >/= 8 g/dl
• Total bilirubin </= 1.5 x the institutional ULN
• AST, ALT </= 3 x the institutional ULN
• Creatinine </= the institutional ULN
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

• A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

  • Has not undergone a hysterectomy or bilateral oophorectomy; or
  • Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
• Patients must be able to swallow and retain oral medications.
• Ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria:

• Chemotherapy, radiotherapy, or other cancer therapy within 4 weeks prior to starting study treatment. Subjects must have recovered from prior treatment-related to toxicities to grade 1 or baseline (excluding alopecia and clinically stable toxicities requiring ongoing medical management, such as hypothyroidism from prior immune checkpoint inhibitor treatment).
• Subjects may not be receiving any other investigational agents for the treatment of the cancer under study.
• Brain metastases
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to Lynparza or other agents used in study.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
• Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lynparza; Lynparza taken orally at a dose of 300mg twice daily for 7 days	Drug: Lynparza; Lynparza taken orally at a dose of 300mg twice daily for 7 days; Other Names: Olaparib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure DNA damage response to PARP inhibition	Paired t-test or Wilcoxon signed-rank test will be used to examine if there is a significant change in ADP ribosylated proteome, DNA damage, apoptosis and change in RAD 51 foci between pre-and post-treatment cancer specimens.	Following 7 days of Lynparza
Characterize changes in ADP ribosylation to PARP inhibition	Spearman rank correlation will be computed to estimate the correlation between the changes in ADP ribosylation with the response (measured by immunohistochemistry: γH2AX and caspase -3 cleavage)	Following 7 days of Lynparza
Correlate DNA damage response to ADP ribosylated proteome	Paired t-test or Wilcoxon signed-rank test will be used to examine if there is a significant change in ADP ribosylated proteome, DNA damage, apoptosis and change in RAD 51 foci between pre-and post-treatment cancer specimens	Following 7 days of Lynparza

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Investigators: Principal Investigator: Jayanthi Lea, MD, University of Texas Southwestern Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): July 23, 2019
• Primary Completion (Actual): June 15, 2021
• Study Completion (Actual): June 15, 2021

Study Registration Dates

• First Submitted: July 29, 2019
• First Submitted That Met QC Criteria: July 29, 2019
• First Posted (Actual): August 1, 2019

Study Record Updates

• Last Update Posted (Actual): March 20, 2023
• Last Update Submitted That Met QC Criteria: March 17, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Poly(ADP-ribose) Polymerase Inhibitors; Olaparib
• Other Study ID Numbers: STU-2019-0769

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes