Pre-Surgical Window Pilot Investigation of the Effect of PARP Inhibition on the Cellular and Molecular Changes in Primary Ovarian and Breast Cancer
Overview
- Phase
- Early Phase 1
- Intervention
- Lynparza
- Conditions
- Ovarian Cancer
- Sponsor
- University of Texas Southwestern Medical Center
- Enrollment
- 14
- Locations
- 1
- Primary Endpoint
- Measure DNA damage response to PARP inhibition
- Status
- Completed
- Last Updated
- 3 years ago
Overview
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.
Investigators
Jayanthi Lea
PROFESSOR - Obstetrics & Gynecology - OB-Gynecologic Oncology
University of Texas Southwestern Medical Center
Eligibility Criteria
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
- •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
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.
Arms & Interventions
Lynparza
Lynparza taken orally at a dose of 300mg twice daily for 7 days
Intervention: Lynparza
Outcomes
Primary Outcomes
Measure DNA damage response to PARP inhibition
Time Frame: Following 7 days of Lynparza
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.
Characterize changes in ADP ribosylation to PARP inhibition
Time Frame: Following 7 days of Lynparza
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)
Correlate DNA damage response to ADP ribosylated proteome
Time Frame: Following 7 days of Lynparza
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