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

NCT04041128 | Completed Early Phase 1 FDA Drug

• 1 other identifier: STU-2019-0769
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Ovarian Cancer; Breast Cancer

Outcome Measures

Primary Outcomes (3)

• 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

Study Arms (1)

Lynparza

EXPERIMENTAL

Lynparza taken orally at a dose of 300mg twice daily for 7 days

Drug: Lynparza

Interventions

Lynparza DRUG

Lynparza taken orally at a dose of 300mg twice daily for 7 days

Also known as: Olaparib

Lynparza

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead

Study Sites (1)

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Ovarian Neoplasms; Breast Neoplasms

Interventions

olaparib

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Jayanthi Lea, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PROFESSOR - Obstetrics & Gynecology - OB-Gynecologic Oncology

Study Record Dates

• First Submitted: July 29, 2019
• First Posted: August 1, 2019
• Study Start: July 23, 2019
• Primary Completion: June 15, 2021
• Study Completion: June 15, 2021
• Last Updated: March 20, 2023

Record last verified: 2023-03

Locations

US (1)