Clinical Trials /

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

NCT04041128

Description:

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.

Related Conditions:
  • Breast Carcinoma
  • Malignant Mixed Mesodermal (Mullerian) Tumor
  • Ovarian Carcinoma
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: STU-2019-0769
  • NCT ID: NCT04041128

Conditions

  • Ovarian Cancer
  • Breast Cancer

Interventions

DrugSynonymsArms
LynparzaOlaparibLynparza

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
LynparzaExperimentalLynparza taken orally at a dose of 300mg twice daily for 7 days
  • 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.
      
Maximum Eligible Age:99 Years
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Measure DNA damage response to PARP inhibition
Time Frame:Following 7 days of Lynparza
Safety Issue:
Description: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.

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Texas Southwestern Medical Center

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