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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04041128
Recruitment Status : Recruiting
First Posted : August 1, 2019
Last Update Posted : May 20, 2020
Sponsor:
Information provided by (Responsible Party):
University of Texas Southwestern Medical Center

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.

Condition or disease Intervention/treatment Phase
Ovarian Cancer Breast Cancer Drug: Lynparza Early Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
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
Actual Study Start Date : July 23, 2019
Estimated Primary Completion Date : July 23, 2023
Estimated Study Completion Date : July 23, 2024


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 Name: Olaparib




Primary Outcome Measures :
  1. 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.

  2. 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)

  3. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04041128


Contacts
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Contact: Tiffany Thomas 214-648-7097 tiffany.thomas@UTSouthwestern.edu

Locations
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United States, Texas
University of Texas Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390
Contact: Tiffany Thomas    214-648-7097    tiffany.thomas@UTSouthwestern.edu   
Sponsors and Collaborators
University of Texas Southwestern Medical Center
Investigators
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Principal Investigator: Jayanthi Lea, MD University of Texas Southwestern Medical Center
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Responsible Party: University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT04041128    
Other Study ID Numbers: STU-2019-0769
First Posted: August 1, 2019    Key Record Dates
Last Update Posted: May 20, 2020
Last Verified: May 2020

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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
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Olaparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents