Veliparib and Topotecan Hydrochloride in Treating Patients with Solid Tumors, Relapsed or Refractory Ovarian Cancer, or Primary Peritoneal Cancer

  • Study type:

    Interventional What is this?

    Describes the nature of a clinical study. Types include:

    • Observational study — observes people and measures outcomes without affecting results.
    • Interventional study (clinical trial) — studies new tests, treatments, drugs, surgical procedures or devices.
    • Medical records research — uses historical information collected from medical records of large groups of people to study how diseases progress and which treatments and surgeries work best.
  • Study phase:

    I/II What is this?

    During the early phases (phases 1 and 2), researchers assess safety, side effects, optimal dosages and risks/benefits. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. They also compare the safety of the new treatment with that of current treatments. Phase 3 trials include large numbers of people to make sure that the result is valid. There are also less common very early (phase 0) and later (phase 4) phases. Phase 0 trials are small trials that help researchers decide if a new agent should be tested in a phase 1 trial. Phase 4 trials look at long-term safety and effectiveness, after a new treatment has been approved and is on the market.

Study IDs

  • Site IRB:

    • Scottsdale/Phoenix, Arizona: 09-000742
    • Jacksonville, Florida: 09-000742
    • Rochester, Minnesota: 09-000742
  • NCT ID:

    NCT01012817
  • Sponsor Protocol Number:

    MC0861

About this study

This phase I/II trial studies the side effects and best dose of veliparib and topotecan hydrochloride and to see how well they work in treating patients with solid tumors, relapsed or refractory ovarian cancer, or primary peritoneal cancer. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as topotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving veliparib with chemotherapy may kill more tumor cells.

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. If you need assistance understanding the eligibility criteria, please contact the study team.

See eligibility criteria

Inclusion Criteria:

  • PHASE I: Adult patients with histologically confirmed solid tumor malignancy that is metastatic or unresectable and for which standard curative measures or other therapy definitely capable of extending life expectancy does not exist
  • PHASE II: All patients enrolled in the Phase II portion of this trial must have a history of biopsy-proven ovarian or primary peritoneal cancer at Mayo Clinic, and radiological evidence of recurrence at a previous site of disease, or biopsy confirmation if the site represents a new site of disease; patients must have received ≤ 2 prior therapeutic regimens and must be either refractory to platinum-based therapy or have relapsed < 1 year after receiving a prior platinum-based regimen
  • Patients must have measurable disease with at least one lesion whose longest diameter can be accurately measured as ≥ 2.0 cm with conventional techniques or as ≥ 1.0 cm with spiral computed topography (CT); if spiral CT is used, it must be used for both pre- and post- treatment tumor assessments
  • Absolute neutrophil count ≥ 1500/mcL
  • Hemoglobin ≥ 9.0 g/dL
  • Platelets ≥ 100,000/mcL
  • Total bilirubin ≤ 1.5x the upper limit of normal (ULN)
  • Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) or serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) ≤ 2.5 x ULN in the absence of hepatic metastasis; SGPT (ALT) ≤ 3 x ULN or SGOT (AST) ≤ 5 x ULN in the presences of hepatic metastasis
  • Creatinine ≤ 1.5 x ULN
  • International normalized ratio (INR) ≤ 1.4 unless receiving therapeutic doses of coumadin
  • Partial thromboplastin time (PTT) ≤ 36 seconds
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0, 1, or 2
  • Ability to provide informed consent
  • Willingness to return to a Mayo Clinic institution for follow up
  • Life expectancy ≥ 12 weeks
  • Willingness to provide the biologic specimens is required by the protocol; this is part of the mandatory translational research component; these specimens include:
    • PHASE I: peripheral blood for plasma pharmacokinetic analysis and peripheral blood mononuclear cell (PBMC) polymer assessment from 0-24 h after drug administration on days 1 and 2 of cycle 1 as well as day 2 of cycle 2; urine for assessment of ABT-888 renal clearance for 24 h after administration of drugs on days 1 and 2 of cycle 1 as well as day 2 of cycle 2; and a pretreatment peripheral blood sample for possible sequencing of the BRCA1, BRCA2 loci as well as possible pharmacogenomic analysis
    • PHASE II: all of the above samples plus a pretreatment biopsy for biological studies and sequence analysis of the BRCA1 and BRCA2 loci
    • Note: The goals of this study include assessment of the biologic effects on surrogate markers of the agent(s) being tested and are, therefore, contingent upon availability of the biologic specimens
  • Women of childbearing potential only: Negative urine or serum pregnancy test done ≤ 7 days prior to registration
  • Able to swallow and absorb the medication

Exclusion Criteria:

  • Known standard therapy for the patient's disease that is potentially curative or definitely capable of extending life expectancy
  • 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 would limit compliance with study requirements
  • Any of the following prior therapies:
    • Chemotherapy ≤ 4 weeks prior to registration
    • Mitomycin C/nitrosoureas ≤ 6 weeks prior to registration
    • Immunotherapy ≤ 4 weeks prior to registration
    • Biologic therapy ≤ 4 weeks prior to registration
    • Radiation therapy ≤ 4 weeks prior to registration
    • Radiation to > 25% of bone marrow
    • Investigational therapy or any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration [FDA]-approved indication and in the context of a research investigation) ≤ 4 weeks prior to registration; subjects with prostate cancer will be permitted to continue hormone therapy
  • Failure to fully recover from acute, reversible effects of prior chemotherapy regardless of interval since last treatment
  • New York Heart Association classification III or IV
  • Known central nervous system (CNS) metastases or seizure disorder; patients with known brain metastases that have been successfully treated and stable for ≥ 6 months without requirement for corticosteroids and without seizure activity will be eligible
  • Any of the following, because this study involves both ABT-888, an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown, and topotecan, an agent that has known genotoxic, mutagenic and teratogenic effects:
    • Pregnant women
    • Nursing women
    • Men or women of childbearing potential who are unwilling to employ adequate contraception
  • Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • Immunocompromised patients (other than that related to the use of corticosteroids) including patients known to be human immunodeficiency virus (HIV) positive
  • Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
  • Other active malignancy, except non-melanotic skin cancer or carcinoma-in-situ of the cervix; NOTE: If there is a history of prior malignancy, they must not be receiving other specific treatment (other than hormonal therapy) for their cancer
  • History of myocardial infarction ≤ 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
  • More than 2 prior chemotherapy regimens for the current malignancy; full dose chemotherapy used in conjunction with concurrent radiation therapy will be included as prior therapy; NOTE: Prior hormonal therapy (e.g. leuprolide, aromatase inhibitors, tamoxifen) will be allowed and not included as a prior chemotherapy

Participating Mayo Clinic locations

Study statuses change often. Please contact us for help.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Michael Menefee, M.D.

Contact us for the latest status

Cancer Center Clinical Trials Referral Office

855-776-0015

Jacksonville, Fla.

Mayo Clinic principal investigator

Michael Menefee, M.D.

Contact us for the latest status

Cancer Center Clinical Trials Referral Office

855-776-0015

Rochester, Minn.

Mayo Clinic principal investigator

Michael Menefee, M.D.

Contact us for the latest status

Cancer Center Clinical Trials Referral Office

855-776-0015