To establish the safety and tolerability of Selinexor when given in combination with
standard chemotherapy regimens.
To determine disease control and progression free survival of Selinexor administered with
standard chemotherapy treatments.
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
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.
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
- 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
- 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
- If participant is in Group M, they will receive: selinexor in combination with
Up to 588 participants will be enrolled in this study. All will take part at MD Anderson.
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
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
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
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.