Study to Compare the Safety and Effectiveness of Treatment Combinations in Patients with Recurrent Ovarian Cancer

Overview

About this study

The primary purpose of this study is to evaluate the effectiveness of the niraparib combinations defined in each cohort-specific supplement, as assessed by confirmed objective response rate (ORR), in patients with advanced, relapsed, high-grade ovarian, fallopian tube, or primary peritoneal cancer.

 

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria: 

  • Patient must be female ≥ 18 years of age, able to understand the study procedures, and agree to participate in the study by providing written informed consent.
  • Patient has histologically diagnosed high-grade recurrent epithelial (e.g., serous, endometrioid, mucinous, clear cell) ovarian, fallopian tube, or primary peritoneal cancer or recurrent carcinosarcoma of the ovary. Patients with high-grade mixed histology are also eligible.
    • Note: Cohorts may exclude some ovarian cancer histologies, as specified in the cohort-specific supplement.
  • For the Phase 1B components: Participant has histologically diagnosed gynecologic malignancy (i.e., any cancer that started in a woman’s reproductive system). Gynecologic malignancies include cervical cancer; endometrial cancer; vaginal cancer; vulvar cancer; high-grade epithelial (i.e., serous, endometrioid, mucinous, clear cell) ovarian, fallopian tube, or primary peritoneal cancer; or advanced carcinosarcoma of the ovary. Participant with high-grade mixed histology is also eligible.
  • The allowed number of prior lines of anticancer therapy for ovarian cancer will be specified in each cohort-specific supplement. Treatment with hormonal agents alone are not counted in the number of lines of therapy. Treatment with single-agent bevacizumab or poly(ADP-ribose) polymerase (PARP) inhibitors given as maintenance is not counted as a separate line of therapy. If a therapeutic regimen is modified or changed for a reason other than lack of response or PD (such as allergic reaction, toxicity, or drug availability), this is not counted as a separate line of therapy.
  • Patient has measurable disease according to RECIST v1.1.
  • Patient has an ECOG performance status of 0 or 1.
  • Patient has adequate organ function, defined as follows:
    • Absolute neutrophil count ≥1,500/μL, without growth factor support (granulocyte colonystimulating factor or granulocyte-macrophage colony-stimulating factor administration is not permitted within 2 weeks of screening);
    • Platelets ≥100,000/μL without platelet transfusion support within 2 weeks of screening;
    • Hemoglobin ≥9 g/dL without transfusion or growth factor (recombinant erythropoietin) within 2 weeks of screening;
    • Serum creatinine ≤ 1.5 × upper limit of normal (ULN) or calculated creatinine clearance ≥ 50 mL/min using Cockcroft-Gault equation;
    • Total bilirubin ≤ 1.5 × ULN, except in patients with Gilbert’s syndrome. Patients with Gilbert’s syndrome may enroll if direct bilirubin is ≤ .5 × ULN for the direct bilirubin;
    • Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 × ULN, unless liver metastases are present, in which case they must be ≤ 5 × ULN;
    • International normalized ratio or prothrombin time (PT) ≤ 1.5 × ULN unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants;
    • Activated partial thromboplastin time ≤ 1.5 × ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants. Patients with known lupus anticoagulant and elevated PTT may be eligible on a case-by-case basis after discussion with the Sponsor’s Medical Monitor.
  • Patient meets the following criteria:
    • Female patient (of childbearing potential) is not breastfeeding, has a negative serum pregnancy test within 72 hours prior to taking study treatment, and agrees to abstain from activities that could result in pregnancy from enrollment through 180 days after the last dose of study treatment; or
      • Note: (a) A urine pregnancy test may be performed if the serum pregnancy result is not available before dosing. (b) Women should not breastfeed or store breastmilk for use, during treatment, and for 30 days after receiving the final dose of study treatment.
    • Female patient is of nonchildbearing potential, other than medical reasons, defined as follows:
      • ≥ 45 years of age and has not had menses for > 1 year;
      • Amenorrheic for < 2 years without a hysterectomy and oophorectomy and a follicle stimulating hormone value in the post-menopausal range upon screening evaluation;
      • Has undergone hysterectomy, bilateral oophorectomy, or tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure; otherwise, the patient must be willing to use highly effective contraception throughout the study, starting with the screening visit through 180 days after the last dose of study therapy.
      • Note: Abstinence is acceptable if this is the established and preferred contraception method for the patient.
  • Patient is willing to undergo a pre-treatment tumor biopsy, unless an appropriate archival tumor tissue (obtained after most recent disease progression) is available. Additionally, patient must be willing to undergo 1 on-treatment biopsy, provided it is deemed safe and feasible by the Investigator.

Exclusion Criteria:

  • Patient has not recovered (e.g., to Grade ≤ 1 or to baseline) from prior chemotherapy-induced AEs.
    • Note: Patient with Grade ≤ 2 neuropathy or alopecia is an exception to this criterion and may qualify for the study.
  • Patient has a known diagnosis of immunodeficiency or is receiving systemic steroid therapy exceeding an equivalent of prednisone 10 mg daily or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.
  • Patient is currently participating in a treatment study or has participated in a study of an investigational agent within 4 weeks of the first dose of treatment.
  • Patient has received prior systemic anticancer therapy including cytotoxic chemotherapy, PARP inhibitor, immune checkpoint inhibitors, hormonal therapy given with the intention to treat ovarian cancer, or biological therapy within 3 weeks of the first dose of study treatment.
  • Patient has received live vaccine within 30 days of planned start of study therapy.
  • Patient has symptomatic uncontrolled brain or leptomeningeal metastases. (To be considered “controlled,” central nervous system [CNS] disease must have undergone treatment [e.g., radiation or chemotherapy] at least 1 month prior to study entry. The patient must not have any new or progressive signs or symptoms related to the CNS disease and must be taking ≤10 mg of prednisone or equivalent per day or no steroids).  Patients who have untreated brain metastases and who are not symptomatic may enroll if the Investigator feels that treatment of these metastases is not indicated. A scan to confirm the absence of brain metastases is not required. Patients with spinal cord compression may be considered if they have received definitive treatment for this and evidence of clinically stable disease (SD) for 28 days prior to the first dose of study treatment.
  • Patient had major surgery within 4 weeks of starting the study or patient has not recovered from any effects of any major surgery.
  • Patient has a known additional malignancy that progressed or required active treatment within the last 2 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cancer that is considered to be low risk for progression by the investigator.
  • Patient is considered a poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease, or active, uncontrolled infection. These include, but are not limited to, significant cardiovascular disease (e.g., significant cardiac conduction abnormalities, myocardial infarction, cardiac arrhythmia or unstable angina within 6 months prior to enrollment, New York Heart Association Grade ≥ 2 congestive heart failure, uncontrolled hypertension, serious cardiac arrhythmia requiring medication, Grade ≥ 2 peripheral vascular disease, and history of cerebrovascular accident within 6 months prior to enrollment), uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, and any psychiatric disorder that prohibits obtaining informed consent.
  • Patient has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, might interfere with the patient’s participation for the full duration of the study treatment, or is not in the best interest of the patient to participate.
  • Patient has known active hepatitis B (e.g., hepatitis B surface antigen reactive) or hepatitis C (e.g., hepatitis C virus ribonucleic acid [qualitative] is detected).

Eligibility last updated 1/26/22. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Andrea Wahner Hendrickson, M.D.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available
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CLS-20449729

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