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Selinexor With Multiple Standard Chemotherapy or Immunotherapy Regimens in Treating Patients With Advanced Malignancies

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02419495
Recruitment Status : Recruiting
First Posted : April 17, 2015
Last Update Posted : February 21, 2021
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
This phase Ib trial studies the side effects and best dose of selinexor when given together with several different standard chemotherapy or immunotherapy regimens in treating patients with malignancies that have spread to other places in the body and usually cannot be cured or controlled with treatment (advanced). Selinexor may stop the growth of cancer cells by blocking enzymes needed for cell growth. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Studying selinexor with different standard chemotherapy or immunotherapy regimens may help doctors learn the side effects and best dose of selinexor that can be given with different types of treatments in one study.

Condition or disease Intervention/treatment Phase
Advanced Malignant Solid Neoplasm Clinical Stage III Cutaneous Melanoma AJCC v8 Clinical Stage IV Cutaneous Melanoma AJCC v8 Fallopian Tube Carcinoma Metastatic Lung Non-Small Cell Carcinoma Metastatic Malignant Solid Neoplasm Metastatic Melanoma Metastatic Renal Cell Carcinoma Ovarian Carcinoma Pathologic Stage III Cutaneous Melanoma AJCC v8 Pathologic Stage IIIA Cutaneous Melanoma AJCC v8 Pathologic Stage IIIB Cutaneous Melanoma AJCC v8 Pathologic Stage IIIC Cutaneous Melanoma AJCC v8 Pathologic Stage IIID Cutaneous Melanoma AJCC v8 Pathologic Stage IV Cutaneous Melanoma AJCC v8 Primary Peritoneal Carcinoma Stage III Lung Cancer AJCC v8 Stage III Renal Cell Cancer AJCC v8 Stage IIIA Lung Cancer AJCC v8 Stage IIIB Lung Cancer AJCC v8 Stage IIIC Lung Cancer AJCC v8 Stage IV Lung Cancer AJCC v8 Stage IV Renal Cell Cancer AJCC v8 Stage IVA Lung Cancer AJCC v8 Stage IVB Lung Cancer AJCC v8 Triple-Negative Breast Carcinoma Unresectable Lung Non-Small Cell Carcinoma Unresectable Melanoma Unresectable Renal Cell Carcinoma Drug: Capecitabine Drug: Carboplatin Drug: Cyclophosphamide Drug: Doxorubicin Drug: Eribulin Drug: Fluorouracil Biological: Ipilimumab Drug: Irinotecan Hydrochloride Drug: Leucovorin Calcium Biological: Nivolumab Drug: Olaparib Drug: Oxaliplatin Drug: Paclitaxel Biological: Pembrolizumab Drug: Pemetrexed Drug: Selinexor Drug: Topotecan Phase 1

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Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 390 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase IB Study to Evaluate the Safety of Selinexor (KPT-330) in Combination With Multiple Standard Chemotherapy or Immunotherapy Agents in Patients With Advanced Malignancies
Actual Study Start Date : June 26, 2015
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : December 31, 2021


Arm Intervention/treatment
Experimental: Arm A (selinexor, carboplatin) (ARM CLOSED)
Patients receive selinexor PO on days 1, 8, and 15 and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After 6 cycles, patients can continue single agent selinexor until disease progression.
Drug: Carboplatin
Given IV
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carboplatinum
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo

Drug: Selinexor
Given PO
Other Names:
  • ATG-010
  • CRM1 Nuclear Export Inhibitor KPT-330
  • KPT-330
  • Selective Inhibitor of Nuclear Export KPT-330
  • SINE KPT-330
  • Xpovio

Experimental: Arm B (selinexor, paclitaxel)
Patients receive selinexor PO twice weekly (e.g. Monday/Wednesday or Tuesday/Thursday or Wednesday/Friday or Thursday/Saturday or Friday/Sunday) on days 1-14. Patients then receive selinexor PO on days 1, 3, 8 and 10 and paclitaxel IV over 3 hours on days 1 and 8. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. After 8 cycles of combination treatment, patients can continue single agent selinexor until disease progression.
Drug: Paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • Bristaxol
  • Praxel
  • Taxol
  • Taxol Konzentrat

Drug: Selinexor
Given PO
Other Names:
  • ATG-010
  • CRM1 Nuclear Export Inhibitor KPT-330
  • KPT-330
  • Selective Inhibitor of Nuclear Export KPT-330
  • SINE KPT-330
  • Xpovio

Experimental: Arm C (selinexor, eribulin)
Patients receive selinexor PO on days 1, 8, and 15 and eribulin IV over 1 hour on days 1 and 8. Combination treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After 6 cycles, patients can continue single agent selinexor until disease progression.
Drug: Eribulin
Given IV
Other Name: ER-086526

Drug: Selinexor
Given PO
Other Names:
  • ATG-010
  • CRM1 Nuclear Export Inhibitor KPT-330
  • KPT-330
  • Selective Inhibitor of Nuclear Export KPT-330
  • SINE KPT-330
  • Xpovio

Experimental: Arm D (selinexor, doxorubicin, cyclophosphamide) (ARM CLOSED)
Patients receive selinexor PO on days 1, 8, and 15, doxorubicin IV over 90 minutes and cyclophosphamide IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After 6 cycles, patients can continue single agent selinexor until disease progression.
Drug: Cyclophosphamide
Given IV
Other Names:
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CTX
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamide Monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Cytoxan
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719

Drug: Doxorubicin
Given IV
Other Names:
  • Adriablastin
  • Hydroxydaunomycin
  • Hydroxyl Daunorubicin
  • Hydroxyldaunorubicin

Drug: Selinexor
Given PO
Other Names:
  • ATG-010
  • CRM1 Nuclear Export Inhibitor KPT-330
  • KPT-330
  • Selective Inhibitor of Nuclear Export KPT-330
  • SINE KPT-330
  • Xpovio

Experimental: Arm E (selinexor, carboplatin, paclitaxel) (ARM CLOSED)
Patients receive selinexor PO on days 1, 8, and 15 and carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1. Treatment repeats every 21 days for up to 8 cycles depending con cancer type (6 cycles for non-small cell lung cancer, up to 8 cycles for ovarian cancer and other histological malignancies) in the absence of disease progression or unacceptable toxicity. After 6 to 8 cycles, patients can continue single agent selinexor until disease progression.
Drug: Carboplatin
Given IV
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carboplatinum
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo

Drug: Paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • Bristaxol
  • Praxel
  • Taxol
  • Taxol Konzentrat

Drug: Selinexor
Given PO
Other Names:
  • ATG-010
  • CRM1 Nuclear Export Inhibitor KPT-330
  • KPT-330
  • Selective Inhibitor of Nuclear Export KPT-330
  • SINE KPT-330
  • Xpovio

Experimental: Arm F (selinexor, carboplatin, pemetrexed) (ARM CLOSED)
Patients receive selinexor PO on days 1, 8, and 15 and carboplatin IV over 30 minutes and pemetrexed disodium IV over 10 minutes on day 1. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After 6 cycles, patients can continue single agent selinexor until disease progression.
Drug: Carboplatin
Given IV
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carboplatinum
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo

Drug: Pemetrexed
Given IV
Other Names:
  • MTA
  • Multitargeted Antifolate
  • Pemfexy

Drug: Selinexor
Given PO
Other Names:
  • ATG-010
  • CRM1 Nuclear Export Inhibitor KPT-330
  • KPT-330
  • Selective Inhibitor of Nuclear Export KPT-330
  • SINE KPT-330
  • Xpovio

Experimental: Arm G (selinexor, topotecan hydrochloride) (ARM CLOSED)
Patients receive selinexor PO on days 1, 8, and 15 and topotecan hydrochloride IV over 30 minutes on days 1-5. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. After 8 cycles, patients can continue single agent selinexor until disease progression.
Drug: Selinexor
Given PO
Other Names:
  • ATG-010
  • CRM1 Nuclear Export Inhibitor KPT-330
  • KPT-330
  • Selective Inhibitor of Nuclear Export KPT-330
  • SINE KPT-330
  • Xpovio

Drug: Topotecan
Given IV
Other Names:
  • Hycamptamine
  • Topotecan Lactone

Experimental: Arm H (selinexor, FOLFIRI) (ARM CLOSED)
Patients receive selinexor PO on days 1, 8, 15 and 22, irinotecan hydrochloride IV over 90 minutes, fluorouracil IV continuously over 48 hours and leucovorin calcium IV over 2 hours on days 1 and 15. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After 6 cycles, patients can continue single agent selinexor until disease progression.
Drug: Fluorouracil
Given IV
Other Names:
  • 5 Fluorouracil
  • 5 Fluorouracilum
  • 5 FU
  • 5-Fluoro-2,4(1H, 3H)-pyrimidinedione
  • 5-Fluorouracil
  • 5-Fluracil
  • 5-Fu
  • 5FU
  • AccuSite
  • Carac
  • Fluoro Uracil
  • Fluouracil
  • Flurablastin
  • Fluracedyl
  • Fluracil
  • Fluril
  • Fluroblastin
  • Ribofluor
  • Ro 2-9757
  • Ro-2-9757

Drug: Irinotecan Hydrochloride
Given IV
Other Names:
  • Campto
  • Camptosar
  • Camptothecin 11
  • Camptothecin-11
  • CPT 11
  • CPT-11
  • Irinomedac
  • Irinotecan Hydrochloride Trihydrate
  • Irinotecan Monohydrochloride Trihydrate
  • U-101440E

Drug: Leucovorin Calcium
Given IV
Other Names:
  • Adinepar
  • Calcifolin
  • Calcium (6S)-Folinate
  • Calcium Folinate
  • Calcium Leucovorin
  • Calfolex
  • Calinat
  • Cehafolin
  • Citofolin
  • Citrec
  • Citrovorum Factor
  • Cromatonbic Folinico
  • Dalisol
  • Disintox
  • Divical
  • Ecofol
  • Emovis
  • Factor, Citrovorum
  • Flynoken A
  • Folaren
  • Folaxin
  • FOLI-cell
  • Foliben
  • Folidan
  • Folidar
  • Folinac
  • Folinate Calcium
  • folinic acid
  • Folinic Acid Calcium Salt Pentahydrate
  • Folinoral
  • Folinvit
  • Foliplus
  • Folix
  • Imo
  • Lederfolat
  • Lederfolin
  • Leucosar
  • leucovorin
  • Rescufolin
  • Rescuvolin
  • Tonofolin
  • Wellcovorin

Drug: Selinexor
Given PO
Other Names:
  • ATG-010
  • CRM1 Nuclear Export Inhibitor KPT-330
  • KPT-330
  • Selective Inhibitor of Nuclear Export KPT-330
  • SINE KPT-330
  • Xpovio

Experimental: Arm I (selinexor, irinotecan hydrochloride) (ARM CLOSED)
Patients receive selinexor PO on days 1, 8 and 15 and irinotecan hydrochloride IV over 90 minutes on days 1 and 8. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. After 8 cycles, patients can continue single agent selinexor until disease progression.
Drug: Irinotecan Hydrochloride
Given IV
Other Names:
  • Campto
  • Camptosar
  • Camptothecin 11
  • Camptothecin-11
  • CPT 11
  • CPT-11
  • Irinomedac
  • Irinotecan Hydrochloride Trihydrate
  • Irinotecan Monohydrochloride Trihydrate
  • U-101440E

Drug: Selinexor
Given PO
Other Names:
  • ATG-010
  • CRM1 Nuclear Export Inhibitor KPT-330
  • KPT-330
  • Selective Inhibitor of Nuclear Export KPT-330
  • SINE KPT-330
  • Xpovio

Experimental: Arm J (selinexor, capecitabine, oxaliplatin) (ARM CLOSED)
Patients receive selinexor PO on days 1, 8 and 15, capecitabine PO twice daily (BID) on days 1-14 and oxaliplatin IV over 2 hours on day 1. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. After 8 cycles, patients can continue single agent selinexor until disease progression.
Drug: Capecitabine
Given PO
Other Names:
  • Ro 09-1978/000
  • Xeloda

Drug: Oxaliplatin
Given IV
Other Names:
  • 1-OHP
  • Ai Heng
  • Aiheng
  • Dacotin
  • Dacplat
  • Diaminocyclohexane Oxalatoplatinum
  • Eloxatin
  • Eloxatine
  • JM-83
  • Oxalatoplatin
  • Oxalatoplatinum
  • RP 54780
  • RP-54780
  • SR-96669

Drug: Selinexor
Given PO
Other Names:
  • ATG-010
  • CRM1 Nuclear Export Inhibitor KPT-330
  • KPT-330
  • Selective Inhibitor of Nuclear Export KPT-330
  • SINE KPT-330
  • Xpovio

Experimental: Arm K (selinexor, olaparib) (ARM CLOSED)
Patients receive selinexor PO on days 1, 8, 15, and 22 and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: Olaparib
Given PO
Other Names:
  • AZD 2281
  • AZD-2281
  • AZD2281
  • KU-0059436
  • Lynparza
  • PARP Inhibitor AZD2281

Drug: Selinexor
Given PO
Other Names:
  • ATG-010
  • CRM1 Nuclear Export Inhibitor KPT-330
  • KPT-330
  • Selective Inhibitor of Nuclear Export KPT-330
  • SINE KPT-330
  • Xpovio

Experimental: Arm L (selinexor, pembrolizumab)
Patients receive selinexor PO twice weekly (e.g. Monday/Wednesday or Tuesday/Thursday or Wednesday/Friday or Thursday/Saturday or Friday/Sunday) and pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Biological: Pembrolizumab
Given IV
Other Names:
  • Keytruda
  • Lambrolizumab
  • MK-3475
  • SCH 900475

Drug: Selinexor
Given PO
Other Names:
  • ATG-010
  • CRM1 Nuclear Export Inhibitor KPT-330
  • KPT-330
  • Selective Inhibitor of Nuclear Export KPT-330
  • SINE KPT-330
  • Xpovio

Experimental: Arm M (selinexor, nivolumab
Patients receive selinexor PO twice weekly (e.g. Monday/Wednesday or Tuesday/Thursday or Wednesday/Friday or Thursday/Saturday or Friday/Sunday) and nivolumab IV over 30 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo

Drug: Selinexor
Given PO
Other Names:
  • ATG-010
  • CRM1 Nuclear Export Inhibitor KPT-330
  • KPT-330
  • Selective Inhibitor of Nuclear Export KPT-330
  • SINE KPT-330
  • Xpovio

Experimental: Arm P (selinexor, nivolumab, ipilimumab)
Patients receive selinexor PO on days 1, 8, 15, 22, 29, and 36, nivolumab IV over 30 minutes on days 1, 15, and 29, and ipilimumab PO QD on day 1. Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
Biological: Ipilimumab
Given IV
Other Names:
  • Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody
  • BMS-734016
  • Ipilimumab Biosimilar CS1002
  • MDX-010
  • MDX-CTLA4
  • Yervoy

Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo

Drug: Selinexor
Given PO
Other Names:
  • ATG-010
  • CRM1 Nuclear Export Inhibitor KPT-330
  • KPT-330
  • Selective Inhibitor of Nuclear Export KPT-330
  • SINE KPT-330
  • Xpovio

Experimental: Arms N and O (selinexor, nivolumab, ipilimumab)
Patients receive selinexor PO on days 1, 8, and 15, nivolumab IV over 30 minutes on day 1, and ipilimumab PO QD on day 1. Cycles repeat every 3 weeks for 4 cycles. Starting cycle 5, patients receive selinexor PO on days 1, 8, 15, and 22 and nivolumab IV over 30 minutes on day 1. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Biological: Ipilimumab
Given IV
Other Names:
  • Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody
  • BMS-734016
  • Ipilimumab Biosimilar CS1002
  • MDX-010
  • MDX-CTLA4
  • Yervoy

Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo

Drug: Selinexor
Given PO
Other Names:
  • ATG-010
  • CRM1 Nuclear Export Inhibitor KPT-330
  • KPT-330
  • Selective Inhibitor of Nuclear Export KPT-330
  • SINE KPT-330
  • Xpovio




Primary Outcome Measures :
  1. Incidence of adverse events [ Time Frame: Up to 3 years ]
    Will be graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.


Secondary Outcome Measures :
  1. Disease control rate (complete response, partial response + stable disease for at least 6 months [ Time Frame: Up to 3 years ]
    Assessed according to Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 criteria). Estimated separately for each cohort with appropriate 95% confidence intervals.

  2. Objective tumor response rate (complete response + partial response) [ Time Frame: Up to 3 years ]
    Assessed according to RECIST 1.1 criteria. Estimated separately for each cohort with appropriate 95% confidence intervals.

  3. Progression-free survival (PFS) [ Time Frame: The time between the course 1 start date and the date of disease progression or death, whichever is reported first, assessed up to 3 years ]
    PFS distribution will be estimated using the Kaplan-Meier product limit method and summary measures such as the median value and probabilities will be reported at selected times (with appropriate 95% confidence intervals).

  4. Overall survival (OS) [ Time Frame: Up to 3 years ]
    OS distribution will be estimated using the Kaplan-Meier product limit method and summary measures such as the median value and probabilities will be reported at selected times (with appropriate 95% confidence intervals).

  5. Incidence of adverse events [ Time Frame: Up to 3 years ]
    Will be graded according to NCI CTCAE version 4.03.


Other Outcome Measures:
  1. Serial mutations in biopsies [ Time Frame: Up to 30 days after last dose of treatment ]
  2. Severity of nausea and vomiting [ Time Frame: Up to 3 years ]
  3. Change in weight [ Time Frame: Baseline up to 3 years ]


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Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed malignant neoplasms (not including hematological malignancies and brain tumors) untreated or previously treated requiring further treatment; patients in Arm L (pembrolizumab), Arm M (nivolumab), and Arms N, O, P (nivolumab and ipilimumab) that have Food and Drug Administration (FDA)-approved indications for nivolumab, ipilimumab, and pembrolizumab do not have to fail first line nivolumab, ipilimumab, or pembrolizumab, and these patients may be treatment naïve if they have disease where pembrolizumab or nivolumab are FDA approved for the first-line setting
  • For all arms except Arm L (pembrolizumab), Arm M (nivolumab), and Arms N, O, P (nivolumab and ipilimumab) 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
  • Patients must have measurable disease (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1)
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
  • The patient must be recovered from a prior major surgery; the major surgery must be performed at least 4 weeks prior to consent date
  • Platelets >= 125 x 10^9/L (For Arm L pembrolizumab, Arm M nivolumab and Arms N, O, P [nivolumab and ipilimumab] and expansion cohorts for all arms, platelets >= 100 x 10^9/L)
  • Hemoglobin >= 10 g/dL (For Arm L pembrolizumab, Arm M nivolumab and Arms N, O, P [nivolumab and ipilimumab] and expansion cohorts for all arms, hemoglobin >= 9 g/dL)
  • Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (For Arm L pembrolizumab, Arm M nivolumab and Arms N, O, P [nivolumab and ipilimumab], ANC >= 1.0 x 10^9/L)
  • Transfusions and growth factors are allowed
  • Alanine transaminase (alanine aminotransferase [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)
  • Renal function defined as a calculated or measured glomerular filtration rate (GFR) >= 30 mL/min. For patients with renal cell carcinoma (RCC), the GFR may be defined as >= 25 mL/min
  • 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
  • Life expectancy of at least 12 weeks
  • Able to swallow and retain oral medication
  • Patients must give informed consent according to the rules and regulations of the individual participating sites
  • 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
  • For the Arm B (paclitaxel) expansion cohort, patients must have ovarian carcinoma, fallopian tube, or peritonea carcinoma
  • For Arm C (eribulin) expansion cohort, patients must have triple negative breast cancer (eribulin naive)
  • For Arm M (nivolumab) expansion phase, patients must have biopsiable disease
  • For the Arm N (nivolumab and ipilimumab), patients must have metastatic or unresectable renal cell carcinoma (RCC)
  • For the Arm O (nivolumab and ipilimumab) escalation and expansion Cohort O-1, patients must have metastatic or unresectable melanoma
  • For the Arm O (nivolumab and ipilimumab) expansion Cohort O-2, patients must have metastatic or advanced solid tumors (non-melanoma, non-renal cell carcinoma, or non- non-small cell lung carcinoma)
  • For the Arm P (nivolumab and ipilimumab), patients must have metastatic or unresectable non-small cell lung carcinoma (NSCLC)

Exclusion Criteria:

  • Evidence of complete or partial bowel obstruction
  • Patients with primary central nervous system (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)
  • Need of total parenteral nutrition
  • Prior treatment with an agent targeting the exportin
  • Allergic to selinexor or any of the chemotherapy intended to receive
  • Pregnancy or lactation
  • Radiation (except planned or ongoing palliative radiation to bone outside of the region of measurable disease) =< 3 weeks prior to study drug administration date
  • Chemotherapy, or immunotherapy or any other systemic anticancer therapy =< 3 weeks prior to study drug administration date; patients receiving anti-PD-1 treatment, and continue to receiving this treatment in combination with selinexor (Arms L, M, N, O, and P), can start receiving the selinexor and anti-PD-1 combination without washout of the prior anti-PD-1 antibody
  • 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)
  • Major surgery within four weeks before consent date
  • 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 atrioventricular [AV] block or asymptomatic left anterior fascicular block [LAFB]/right bundle branch block [RBBB] will not be excluded), or congestive heart failure (CHF) of New York Heart Association (NYHA) class >= 3, or myocardial infarction (MI) within 3 months of consent date
  • 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
  • Significantly diseased (as determined by the principal investigator [PI] or treating physician) or obstructed gastrointestinal tract or uncontrolled vomiting or diarrhea
  • Treatment with an investigational anti-cancer study drug within 3 weeks prior to study drug administration date
  • Concurrent therapy with approved or investigational anticancer therapeutics
  • Medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
  • 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)
  • For Arms L (pembrolizumab) and M (nivolumab), and Arms N, O, P (nivolumab and ipilimumab), subjects with an active, known or suspected autoimmune disease; subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
  • For Arms L (pembrolizumab) and M (nivolumab), and Arms N, O, P (nivolumab and ipilimumab), subjects receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or other form of immunosuppressive therapy within 7 days before the first dose of study treatment; use of inhaled or topical steroids or systemic corticosteroids =< 10 mg is permitted; in addition, physiologic steroid replacement with hydrocortisone is allowed
  • For Arms L (pembrolizumab) and M (nivolumab), and Arms N, O, P (nivolumab and ipilimumab), history of a prior grade 3 or 4 immune-related adverse event (irAE) or any grade ocular irAE from prior immunotherapy
  • For the Arm O (nivolumab and ipilimumab) expansion Cohort O-2, patients must not have melanoma, RCC, or NSCLC

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02419495


Contacts
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Contact: Aung Naing 713-563-0803 anaing@mdanderson.org

Locations
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United States, Texas
MD Anderson in The Woodlands Recruiting
Conroe, Texas, United States, 77384
Contact: Aung Naing    713-563-0803    anaing@mdanderson.org   
Principal Investigator: Aung Naing         
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Aung Naing    713-563-0803    anaing@mdanderson.org   
Principal Investigator: Aung Naing         
MD Anderson West Houston Recruiting
Houston, Texas, United States, 77079
Contact: Aung Naing    713-563-0803    anaing@mdanderson.org   
Principal Investigator: Aung Naing         
MD Anderson League City Recruiting
League City, Texas, United States, 77573
Contact: Aung Naing    713-563-0803    anaing@mdanderson.org   
Principal Investigator: Aung Naing         
MD Anderson in Sugar Land Recruiting
Sugar Land, Texas, United States, 77478
Contact: Aung Naing    713-563-0803    anaing@mdanderson.org   
Principal Investigator: Aung Naing         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Aung Naing M.D. Anderson Cancer Center
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02419495    
Other Study ID Numbers: 2014-0640
NCI-2015-00693 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2014-0640 ( Other Identifier: M D Anderson Cancer Center )
First Posted: April 17, 2015    Key Record Dates
Last Update Posted: February 21, 2021
Last Verified: February 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma
Lung Neoplasms
Neoplasms
Melanoma
Carcinoma, Renal Cell
Breast Neoplasms
Skin Neoplasms
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Nevi and Melanomas
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Kidney Diseases
Urologic Diseases
Breast Diseases
Skin Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms