The goal of this clinical trial is to learn about the side effects and effectiveness of this novel four-drug combination of chemotherapy (decitabine, selinexor, carboplatin and paclitaxel) on patients with relapsed ovarian, fallopian or primary peritoneal carcinoma.
Recently the investigators have found that the combination of decitabine and selinexor, two Food and Drug Administration (FDA) approved chemotherapy agents, may prevent or reverse the development of drug resistance and further the remissions and duration of remissions with standard ovarian cancer chemotherapy with carboplatin and paclitaxel. As decitabine and selinexor are not FDA approved for the participant's cancer, these agents are investigational.
Participants must be greater than or equal to 18 years of age
Participants must have an Eastern Cooperative Oncology Group (ECOG) Performance Status PS less than or equal to 2.
Participants must have histological or cytological proven epithelial ovarian cancer, fallopian tube or primary peritoneal carcinoma with relapse or disease progression after prior treatment by exam, computed tomography (CT), PET/CT, or magnetic resonance imaging (MRI) may be enrolled. All cell types including clear cell carcinoma are eligible.
Participants must have failed or relapsed after a platinum and taxane containing combination
Participants must not have received Selinexor or another XPO1 inhibitor previously.
Participants must not have had any concurrent medical condition or disease (eg, uncontrolled active hypertension, uncontrolled active diabetes, active systemic infection, etc.)
Participants must not have uncontrolled active infection. Participants on prophylactic antibiotics or with a controlled infection within 1 week prior to C1D1 are acceptable.
Participants must not have known intolerance, hypersensitivity, or contraindication to platinum or taxane therapy
Single group
Decitabine
DrugDecitabine is classified as hypomethylation agents. It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow.
Carboplatin
DrugCarboplatin is classified as an alkylating agent that is used to treat ovarian cancer.
Paclitaxel
DrugPaclitaxel is classified as a "plant alkaloid," a "taxane" and an "antimicrotubule agent."
Selinexor
DrugSelinexor is in a class of medications called selective inhibitors of nuclear export (SINE). It works by killing cancer cells.
40 participants evaluated for safety with treatment-related adverse events and grading using CTCAE 4.3.
To determine the safety of two agents in combination to reverse platinum resistance in ovarian cancer: the hypomethylating agent, decitabine, and the nuclear export receptor XPO1 inhibitor, selinexor, combined with carboplatin and paclitaxel in patients with relapsed/refractory epithelial ovarian carcinoma
40 participants evaluated to determine the clinical efficacy of this novel regimen in both platinum sensitive and resistant recurrent disease as measured by response rates. Response rates (partial response [PR] and complete response [CR])
To determine the clinical efficacy of this novel regimen in both platinum sensitive and resistant disease as measured by response rates
40 participants evaluated to determine the cellular immune effects of this combination. B and T cell numbers and subsets after therapy.
This is an exploratory endpoint to determine if there is a potential immune enhancement of this combination on numbers of Immune T and B cells after therapy (15% or higher increase in cell numbers/mm3) when compared to pre-treatment values and whether this correlates to response rates.
40 participants evaluated for tolerability with treatment-related adverse events and grading using CTCAE 4.3.
To determine the tolerability of two agents that reverse platinum sensitivity in ovarian cancer, the hypomethylating agent, decitabine, and the nuclear export receptor XPO1 inhibitor, Selinexor, combined with carboplatin and Taxol in patients with relapsed/refractory epithelial ovarian carcinoma
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Loyola University
Lead sponsor
Karyopharm Therapeutics Inc
Collaborator
