Clinical Trials /

A Study of Olaparib Prior to Surgery and Chemotherapy in Ovarian, Primary Peritoneal, and Fallopian Tube Cancer

NCT02489006

Description:

This is a study that will look at the effects and how useful investigational drug olaparib is as a neoadjuvant treatment (treatment given as to shrink a tumor before the main treatment) prior to surgery in patients with recurrent ovarian, primary peritoneal or fallopian tube cancer.

Related Conditions:
  • Fallopian Tube Carcinoma
  • High Grade Ovarian Serous Adenocarcinoma
  • Primary Peritoneal Serous Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of Olaparib Prior to Surgery and Chemotherapy in Ovarian, Primary Peritoneal, and Fallopian Tube Cancer
  • Official Title: A Phase II, Open-Label, Randomized, Multi-Centre Study, of Neoadjuvant Olaparib in Patients With Platinum Sensitive Recurrent High Grade Serous Ovarian/Primary Peritoneal or Fallopian Tube Cancer

Clinical Trial IDs

  • ORG STUDY ID: OZM-058
  • NCT ID: NCT02489006

Conditions

  • Ovarian Cancer
  • Fallopian Tube Cancer
  • Neoadjuvant Treatment
  • Debulking Surgical Procedures

Interventions

DrugSynonymsArms
OlaparibLynparzaOlaparib Prior to Surgery, Chemotherapy/Olaparib Post Surgery
Platinum-based ChemotherapyOlaparib Prior to Surgery, Chemotherapy/Olaparib Post Surgery

Purpose

This is a study that will look at the effects and how useful investigational drug olaparib is as a neoadjuvant treatment (treatment given as to shrink a tumor before the main treatment) prior to surgery in patients with recurrent ovarian, primary peritoneal or fallopian tube cancer.

Detailed Description

      Olaparib belongs to a class of anti-cancer agents known as poly ADP-ribose polymerase (PARP)
      inhibitors. Olaparib is a new type of drug for ovarian cancer. Laboratory tests show that it
      may help slow the growth of ovarian cancer.

      Olaparib works by blocking the PARP protein. PARP is an important protein which tries to fix
      damaged deoxyribonucleic acid (DNA, molecules that contain important instructions for the
      development of cells). Many cancers are thought to develop from damaged DNA. Research has
      shown that PARP inhibitors stop the PARP protein from working, and that sometimes that can
      cause cancer cells to stop growing or die.
    

Trial Arms

NameTypeDescriptionInterventions
Olaparib Prior to Surgery, Chemotherapy/Olaparib Post SurgeryExperimentalOlaparib, orally, at 300 mg twice per day, for 6 weeks (+/- 2 weeks) prior to surgery. Platinum-based chemotherapy chosen by the study doctor and per standard of care after surgery. Olaparib, orally, at 300 mg twice per day, continuously, after chemotherapy.
  • Olaparib
  • Platinum-based Chemotherapy
Olaparib Prior to Surgery and Post SurgeryExperimentalOlaparib, orally, at 300 mg twice per day, for 6 weeks (+/- 2 weeks) prior to surgery and after surgery.
  • Olaparib

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically proven recurrent high grade serous ovarian/primary peritoneal or
             fallopian tube cancer.

          -  Patients must have disease amenable to pre-operative biopsy.

          -  Patients must have disease deemed suitable for surgical debulking.

          -  Patients must have a progression free interval of at least 6 months prior to
             registration.

          -  Patients must have had at least one line of platinum based therapy.

          -  Patients must have shown platinum sensitivity to their last line of platinum therapy

          -  Age >=18 years

          -  ECOG performance status 0-1 within 7 days of registration

          -  Life expectancy of greater than 3 months

          -  Patients must have normal organ and marrow function

          -  Women of child-bearing potential must agree to use adequate contraception prior to
             study entry and for the duration of study participation.

          -  Ability to understand and the willingness to sign a written informed consent document.

          -  Subject's willingness and ability to comply with scheduled visits, treatment plans,
             laboratory tests, and other study procedures.

        Exclusion Criteria:

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to olaparib.

          -  History of allergic reactions attributed to platinum precluding further use.

          -  Radiation therapy within 4 weeks of registration

          -  Use of any other systemic, targeted, immunotherapy, chemotherapy, or investigational
             agents within 4 weeks of registration

          -  Previously received a PARP inhibitor

          -  Other malignancy within the last 2 years with exceptions

          -  Patients considered a poor medical risk due to a serious, uncontrolled medical
             disorder, non-malignant systemic disease or active, uncontrolled infection.

          -  Patients unable to swallow orally administered medication and patients with
             gastrointestinal disorders likely to interfere with absorption of the study
             medication.

          -  Concomitant use of known potent CYP3A4 inhibitors

          -  Concomitant use of known potent CYP3A4 inducers

          -  Other anti-cancer therapy including immunotherapy, hormonal therapy, biological
             therapy, other novel agents or investigational agents

          -  Persistent toxicities (CTCAE v 4.03 grade >2) caused by previous cancer therapy,
             excluding alopecia

          -  Patients with myelodysplastic syndrome/acute myeloid leukemia

          -  Patients with brain metastases

          -  Immunocompromised patients, e.g., patients who are known to be serologically positive
             for human immunodeficiency virus (HIV)

          -  Patients with known active hepatitis (i.e., hepatitis B or C) due to risk of
             transmitting the infection through blood or other body fluids

          -  Pregnant or breastfeeding women

          -  Receipt of live attenuated vaccine within 30 days prior to enrollment

          -  Patients with > Grade 2 hearing impairment as per CTCAE v 4.03

          -  Other severe acute or chronic medical or psychiatric condition or laboratory
             abnormality that may increase the risk associated with study participation or study
             drug administration, or may interfere with the interpretation of study results, and in
             the judgment of the investigator would make the subject inappropriate for entry into
             this study.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Difference in levels of PAR or PARP-1 before and after study treatment
Time Frame:4-8 weeks
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Frequency of adverse events, by description and grade
Time Frame:2.5 years
Safety Issue:
Description:
Measure:Response rate to olaparib in the neoadjuvant period
Time Frame:6 weeks
Safety Issue:
Description:
Measure:Duration of progression free survival with olaparib in comparison to platinum based chemotherapy
Time Frame:2.5 years
Safety Issue:
Description:
Measure:Levels of ctDNA compared to levels of CA125
Time Frame:2.5 years
Safety Issue:
Description:
Measure:Gene expression changes in tumour tissue before and after treatment with Olaparib
Time Frame:2.5 years
Safety Issue:
Description:
Measure:Secondary mutation rate in surgical tumour specimens following PARP therapy and at progression
Time Frame:2.5 years
Safety Issue:
Description:2.5 years
Measure:Changes in blood based biomarkers using ctDNA before, during and after treatment with Olaparib
Time Frame:2.5 years
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University Health Network, Toronto

Last Updated

December 17, 2019