Clinical trial NCT04041128: PARP Inhibition During Pre-surgical Window in Breast/Ovary Cancer
Official title: Pre-Surgical Window Pilot Investigation of the Effect of PARP Inhibition on the Cellular and Molecular Changes in Primary Ovarian and Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Ovarian Cancer
Breast Cancer
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
First posted: 2019-08-01
Enrollment: 14
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.


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 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.

Primary outcomes:
measure: Measure DNA damage response to PARP inhibition
timeFrame: Following 7 days of Lynparza
measure: Characterize changes in ADP ribosylation to PARP inhibition
timeFrame: Following 7 days of Lynparza
measure: Correlate DNA damage response to ADP ribosylated proteome
timeFrame: Following 7 days of Lynparza
Secondary outcomes:
Other outcomes:
Locations:
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
Study officials:
affiliation: University of Texas Southwestern Medical Center
name: Jayanthi Lea, MD
role: PRINCIPAL_INVESTIGATOR
References: