Houston, Texas 77030


Purpose:

Objectives: Primary Objective: To establish the safety and tolerability of Selinexor when given in combination with standard chemotherapy regimens. Secondary Objectives: To determine disease control and progression free survival of Selinexor administered with standard chemotherapy treatments. Exploratory Objectives: To determine the correlation of translational biomarkers To compare serial assessment of mutation status in biopsies obtained at baseline and progression after clinical response to combination therapy


Study summary:

This is an open label, single center Phase IB combination therapy study in metastatic or locally advanced cancers. The addition of Selinexor to multiple standard chemotherapy regimens will be tested in parallel. Two types of patients may be enrolled in this study: (1) advanced staged cancer patients either unresponsive or relapsed following prior standard therapy or for whom there is no known effective therapy; OR (2) advanced stage cancer patients for whom the standard chemotherapy treatment to which Selinexor is added is considered an appropriate and acceptable therapy. Patients who meet these criteria may in some cases have received no prior chemotherapy. Study Groups: If participant is found to be eligible to take part in this study, their doctor will decide which part of the study they will be in based on the type of tumor they have. The study doctor will discuss this with participant. - If participant is in Group A, they will receive selinexor and carboplatin. - If participant is in Group B, they will receive selinexor and paclitaxel. - If participant is in Group C, they will receive selinexor and eribulin. - If participant is in Group D, they will receive selinexor, doxorubicin, and cyclophosphamide. - If participant is in Group E, they will receive selinexor, carboplatin, and paclitaxel. - If participant is in Group F, they will receive selinexor, carboplatin, and pemetrexed. - If participant is in Group G, they will receive selinexor and topotecan. - If participant is in Group H, they will receive selinexor in combination with FOLFIRI. - If participant is in Group I, they will receive selinexor in combination with irinotecan. - If participant is in Group J, they will receive selinexor in combination with XELOX. - If participant is in Group K, they will receive selinexor in combination with olaparib. - If participant is in Group L, they will receive selinexor in combination with pembrolizumab. - If participant is in Group M, they will receive: selinexor in combination with nivolumab. Up to 588 participants will be enrolled in this study. All will take part at MD Anderson.


Criteria:

Inclusion Criteria: 1. Patients must have histologically or cytologically confirmed malignant neoplasms (not including hematological malignancies and brain tumors) untreated or previously treated requiring further treatment. Patients must be refractory to, and intolerant of, established therapy known to provide clinical benefit for their condition. 2. Patients must have failed prior standard curative chemotherapy for their disease. Subjects must have failed, be intolerant to, or be ineligible for any potentially curative approved treatment, irrespective of line of therapy. 3. Patients must have either measurable disease (RECIST 1.1) or evaluable disease (non-measurable lesions) outside irradiated field on CT/MRI. 4. Age >/= 18 years. 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. 6. The patient must be recovered from a prior major surgery. The major surgery must be performed at least 4 weeks prior to consent date. 7. Adequate hematologic function defined as: platelets >/=125 x 10^9/L (For Arm L Pembrolizumab, platelets >/= 100 x 10^9/L), hemoglobin >/= 10 g/dL (For Arm L Pembrolizumab, hemaglobin >/= 9 g/dL), ANC >/= 1.5 x 10^9/L, WBC >/= 3 x 10^9/L, Albumin >/= 3 g/dL. Transfusions and growth factors are allowed. 8. Adequate liver function defined as: Alanine transaminase (ALT) </= 2 x upper normal limit (ULN) (In the expansion cohort, patients with known liver involvement may have ALT </= 5 x ULN), Aspartate aminotransferase (AST) </=2 x ULN (In the expansion cohort, patients with known liver involvement may have AST </= 5 x ULN), Alkaline phosphatase < 4 x ULN, Total Bilirubin </=2 x ULN (In the expansion cohort, patients with Gilbert's syndrome [hereditary indirect hyperbilirubinemia] who must have a total bilirubin of </= 3 x ULN). 9. Renal function defined as a calculated or measured glomerular filtration rate (GFR) >/=30 mL/min. For Arm F Carboplatin and Pemetrexed, GFR >/=45 mL/min. 10. The patient has recovered to Grade </= 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.03 (NCI-CTCAE v4.03) from the effects of recent surgery, radiotherapy, chemotherapy, hormonal therapy, or other targeted therapies, with the exception of alopecia. The exceptions for such effects are allowed lab values of </= Grade 2 specified elsewhere in these inclusion criteria. 11. Life expectancy of at least 12 weeks. 12. Able to swallow and retain oral medication. 13. Patients must give informed consent according to the rules and regulations of the individual participating sites. 14. Negative serum pregnancy test in women of childbearing potential within 7 days of first dose of treatment and patients of child-bearing potential must agree to use effective contraception during/after 3 months post dose. A woman of childbearing potential is defined as a premenopausal female capable of becoming pregnant. This includes women on oral, injectable or mechanical contraception; women who are single and women whose male sexual partners have been vasectomized or whose male sexual partners have received or are utilizing mechanical contraceptive devices. 15. If in Arm D (Doxorubicin and Cyclophosphamide), left ventricular ejection fraction (LVEF) >/= 50% as measured by echocardiogram (ECHO) within 4 weeks prior to study drug administration. Exclusion Criteria: 1. Evidence of complete or partial bowel obstruction. 2. Patients with primary CNS tumor or CNS tumor involvement. However, patients with metastatic CNS tumors may participate in this study if the patient is: > 4 weeks from prior therapy completion (including radiation and/or surgery); Clinically stable with respect to the CNS tumor at the time of study entry; Not receiving steroid therapy in treating CNS tumor or CNS tumor involvement; Not receiving anti-convulsive medications (that were started for brain metastases). 3. Need of Total Parenteral Nutrition. 4. Prior treatment with an agent targeting the Exportin. 5. Allergic to Selinexor or any of the chemotherapy intended to receive. 6. Pregnancy or lactation. 7. Radiation (except planned or ongoing palliative radiation to bone outside of the region of measurable disease) </= 3 weeks prior to study drug administration date. 8. Chemotherapy, or immunotherapy or any other systemic anticancer therapy </=3 weeks prior to study drug administration date. 9. Diagnosis or recurrence of invasive cancer other than the present cancer within 3 years (except basal or squamous cell carcinoma of the skin that has been definitively treated). 10. Major surgery within four weeks before consent date. 11. Unstable cardiovascular function: Symptomatic ischemia (chest pain of cardiac origin), or Uncontrolled clinically significant conduction abnormalities (e.g. ventricular tachycardia on antiarrhythmics are excluded and 1st degree AV block or asymptomatic LAFB/ RBBB will not be excluded), or Congestive heart failure (CHF) of NYHA Class >/= 3, or Myocardial infarction (MI) within 3 months of consent date. 12. Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to the first dose. Active infection with concurrent treatment is acceptable only if the patient is clinically stable. 13. Significantly diseased (as determined by the PI or treating physician) or obstructed gastrointestinal tract or uncontrolled vomiting or diarrhea. 14. Treatment with an investigational anti-cancer study drug within 3 weeks prior to study drug administration date. 15. Concurrent therapy with approved or investigational anticancer therapeutics. 16. Medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results 17. Men whose partner is a woman of child-bearing potential, (i.e. biologically able to conceive), and who is not employing two forms of highly effective contraception. Highly effective contraception (e.g. male condom with spermicide, diaphragm with spermicide, intra-uterine device) must be used by both sexes during the study and must be continued for 3 months after the end of study treatment. Women of child-bearing potential is defined as sexually mature women who are not surgically sterile or who have not been naturally postmenopausal for at least 12 consecutive months (e.g., who has had menses any time in the preceding 12 consecutive months). 18. If in Arm D (Doxorubicin and Cyclophosphamide), patients with prior cumulative doxorubicin dose of >/= 260 mg/m2.


NCT ID:

NCT02419495


Primary Contact:

Principal Investigator
Aung Naing, MD
M.D. Anderson Cancer Center

Aung Naing, MD
Phone: 713-563-1930


Backup Contact:

N/A


Location Contact:

Houston, Texas 77030
United States



There is no listed contact information for this specific location.

Site Status: Recruiting


Data Source: ClinicalTrials.gov

Date Processed: November 22, 2017

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